Source: http://www.google.com/patents/US7790905?dq=6,970,917
Timestamp: 2015-05-27 14:51:09
Document Index: 721269127

Matched Legal Cases: ['Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60']

Patent US7790905 - Pharmaceutical propylene glycol solvate compositions - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inAdvanced Patent SearchPatentsThe invention relates to pharmaceutical compositions comprising propylene glycol solvates of APIs....http://www.google.com/patents/US7790905?utm_source=gb-gplus-sharePatent US7790905 - Pharmaceutical propylene glycol solvate compositionsAdvanced Patent SearchPublication numberUS7790905 B2Publication typeGrantApplication numberUS 10/747,742Publication dateSep 7, 2010Filing dateDec 29, 2003Priority dateFeb 15, 2002Fee statusPaidAlso published asUS20070015841Publication number10747742, 747742, US 7790905 B2, US 7790905B2, US-B2-7790905, US7790905 B2, US7790905B2InventorsMark Tawa, �rn Almarsson, Julius RemenarOriginal AssigneeMcneil-Ppc, Inc.Export CitationBiBTeX, EndNote, RefManPatent Citations (104), Non-Patent Citations (356), Referenced by (15), Classifications (5), Legal Events (4) External Links: USPTO, USPTO Assignment, EspacenetPharmaceutical propylene glycol solvate compositions
US 7790905 B2Abstract
The invention relates to pharmaceutical compositions comprising propylene glycol solvates of APIs.
1. A propylene glycol solvate of a sodium salt of celecoxib having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol.
2. A propylene glycol solvate of celecoxib sodium trihydrate having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol: 3 hydrate.
3. A propylene glycol solvate of celecoxib selected from:
a) a propylene glycol solvate of celecoxib sodium trihydrate characterized by a thermogravimetric analysis of FIG. 18 or FIG. 20, said propylene glycol solvate of celecoxib sodium trihydrate having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol: 3 hydrate; or
b) a propylene glycol solvate of a sodium salt of celecoxib characterized by a thermogravimetric analysis of FIG. 1, said propylene glycol solvate of a sodium salt of celecoxib having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol.
4. The propylene glycol solvate of celecoxib according to claim 3, wherein the form is a propylene glycol solvate of celecoxib sodium trihydrate characterized by a thermogravimetric analysis of FIG. 18, said propylene glycol solvate of celecoxib sodium trihydrate having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol: 3 hydrate.
5. The propylene glycol solvate of celecoxib according to claim 3, wherein the form is a propylene glycol solvate of celecoxib sodium trihydrate characterized by a thermogravimetric analysis of FIG. 20, said propylene glycol solvate of celecoxib sodium trihydrate having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol: 3 hydrate.
6. The propylene glycol solvate of celecoxib according to claim 3, wherein the form is a propylene glycol solvate of a sodium salt of celecoxib characterized by a thermogravimetric analysis of FIG. 1, said propylene glycol solvate of a sodium salt of celecoxib having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol.
7. A propylene glycol solvate of celecoxib selected from:
a) a propylene glycol solvate of celecoxib sodium trihydrate characterized by the PXRD pattern of FIG. 19 or FIG. 21, said propylene glycol solvate of celecoxib sodium trihydrate having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol: 3 hydrate; or
b) a propylene glycol solvate of a sodium salt of celecoxib characterized by a PXRD pattern of FIG. 2A, 2B, 2C or 2D, said propylene glycol solvate of a sodium salt of celecoxib having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol.
8. The propylene glycol solvate according to claim 7, wherein said propylene glycol solvate is a propylene glycol solvate of celecoxib sodium trihydrate characterized by the PXRD pattern of FIG. 19 and having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol: 3 hydrate.
9. The propylene glycol solvate according to claim 7, wherein said propylene glycol solvate is a propylene glycol solvate of celecoxib sodium trihydrate characterized by the PXRD pattern of FIG. 21 and having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol: 3 hydrate.
10. The propylene glycol solvate according to claim 7, wherein said propylene glycol solvate is a propylene glycol solvate of a sodium salt of celecoxib, said propylene glycol solvate of a sodium salt of celecoxib characterized by a PXRD pattern of FIG. 2A, 2B, 2C or 2D and having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol.
11. The propylene glycol solvate according to claim 7, wherein said propylene glycol solvate is a propylene glycol solvate of a sodium salt of celecoxib and said composition is characterized by the PXRD pattern of FIG. 2A.
12. The propylene glycol solvate according to claim 7, wherein said propylene glycol solvate is a propylene glycol solvate of a sodium salt of celecoxib and said composition is characterized by the PXRD pattern of FIG. 2B.
13. The propylene glycol solvate according to claim 7, wherein said propylene glycol solvate is a propylene glycol solvate of a sodium salt of celecoxib and said composition is characterized by the PXRD pattern of FIG. 2C.
14. The propylene glycol solvate according to claim 7, wherein said propylene glycol solvate is a propylene glycol solvate of a sodium salt of celecoxib and said composition is characterized by the PXRD pattern of FIG. 2D.
15. A pharmaceutical composition comprising an excipient and a form of a propylene glycol solvate of celecoxib selected from:
16. The composition according to claim 15, wherein said form is a propylene glycol solvate of celecoxib sodium trihydrate characterized by the PXRD pattern of FIG. 19 or FIG. 21 and having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol: 3 hydrate.
17. The composition according to claim 15, wherein said form is a propylene glycol solvate of a sodium salt of celecoxib, said propylene glycol solvate of a sodium salt of celecoxib characterized by a PXRD pattern of FIG. 2A, 2B, 2C or 2D and having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol.
18. The composition according to claim 17, wherein said form is a propylene glycol solvate of a sodium salt of celecoxib and said composition is characterized by the PXRD pattern of FIG. 2A.
19. The composition according to claim 17, wherein said form is a propylene glycol solvate of a sodium salt of celecoxib and said composition is characterized by the PXRD pattern of FIG. 2B.
20. The composition according to claim 17, wherein said form is a propylene glycol solvate of a sodium salt of celecoxib and said composition is characterized by the PXRD pattern of FIG. 2C.
21. The composition according to claim 16, wherein said form is a propylene glycol solvate of celecoxib sodium trihydrate characterized by the PXRD pattern of FIG. 19 and having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol: 3 hydrate.
22. The composition according to claim 16, wherein said form is a propylene glycol solvate of celecoxib sodium trihydrate characterized by the PXRD pattern of FIG. 21 and having a stoichiometric ratio of 1 celecoxib: 1 sodium: 1 propylene glycol: 3 hydrate.
23. The composition according to claim 17, wherein said form is a propylene glycol solvate of a sodium salt of celecoxib and said composition is characterized by the PXRD pattern of FIG. 2D.
This application claims the benefit of U.S. Provisional Application No. 60/486,713, filed Jul. 11, 2003, U.S. Provisional Application No. 60/459,501, filed Apr. 1, 2003, U.S. Provisional Application No. 60/456,608, filed Mar. 21, 2003, U.S. Provisional Application No. 60/456,027, filed Mar. 18, 2003, U.S. Provisional Application No. 60/441,335, filed Jan. 21, 2003, and U.S. Provisional Application No. 60/437,516, filed Dec. 30, 2002. The content of each of these applications is hereby incorporated by reference in its entirety.
Propylene glycol (1,2-propanediol) is a known substance which is a liquid at ambient temperature. As far as the applicants are aware, propylene glycol is not generally well-known for use in the formation of solvates. U.S. Pat. No. 3,970,651 does disclose the use of propylene glycol in the formation of a crystalline cephalosporin derivative. According to this disclosure a propylene glycolate derivative of a specific cephalosporin zwitterion may be formed in the presence of propylene glycol at acidic pH. This disclosure indicates that the propylene glycol derivative is more stable in solid form than the corresponding ethanolate, especially having excellent colour stability and thermal stability. No other solvates are disclosed in this US patent other than the specific solvate of cephalosporin.
In pharmaceutical formulations certain chemical classes of drugs pose particular problems in preparing pharmaceutical formulations for medical use. One such problem arises in the case of hygroscopic drugs, which tend to absorb water from the air. This is disadvantageous because it makes storage of the drug difficult and can cause degradation of the drug in some cases. Such compounds must be handled in controlled humidity environments during manufacture in order to prevent potency errors due to the changing weight of the drug. The final product must be packaged in individual moisture resistant blisters in order to prevent changes in or degradation of the product. Another problem arises from variable hydration states: molecules may change to a more or less stable form as water, a volatile liquid, is lost. Such changes have been known to cause some hydrates to become amorphous. Likewise, absorption of water by a hygroscopic molecule can plasticize the system and lead to recrystallization as a less stable polymorph.
Solvates are rarely used in pharmaceuticals because the solvents are usually volatile thus making it difficult to maintain the solvent in the crystal. If one were to desolvate a pharmaceutical solvate or if it desolvated due to storage conditions or otherwise, it could lead to the formation of multiple polymorphs or complete collapse of the crystal structure, forming an amorphous compound with different physical properties. Obviously, this batch-to-batch variability and questionable shelf life is undesired. Typically people find solvates of common solvents, such as propanol and ethanol. Propylene glycol is similar in structure to propanol, but is not thought of as a solvent. Propylene glycol solvates of the present invention desolvate only at considerably higher temperatures and harsher conditions than traditional solvates. Propylene glycol solvates are also pharmaceutically acceptable in much larger amounts than one would expose people to with a traditional solvate. Thus, the propylene glycol solvates of the present invention have characteristics that are vastly superior to traditional solvates.
In a first aspect, the present invention provides a pharmaceutical composition comprising a propylene glycol solvate of a drug which is hygroscopic or has low aqueous solubility. It has surprisingly been found that by using propylene glycol to form a solvate of a hygroscopic drug, the hygroscopicity of the drug is decreased and/or the stability and aqueous solubility is increased. The drug is therefore much easier to formulate and store than its counterpart untreated or hydrated form.
Advantageously, the powder X-ray diffraction (PXRD) spectrum of the composition according to the invention differs from the corresponding powder X-ray diffraction spectrum of unsolvated drug by at least one property selected from:
(i) a loss of at least one peak; (ii) shifting of more than half the peaks at the 2-theta angle by at least 0.2, 0.3, 0.4, or 0.5 degrees; or (iii) formation of at least one new peak. It is preferred that the solvate is stable to temperatures of up to 50 degrees C. under a stream of nitrogen gas in a thermogravimetric analysis apparatus.
Primaxin IV and IM
Dalfopristin/
Quinopristin
phosphate (ester
prodrug)
(P&U)
Pfizerpen Injection
(Medeva)
(Boehringer-
(a) contacting propylene glycol with a drug in solution; (b) crystallizing a propylene glycol solvate of the drug from the solution; and (c) isolating the solvate. (the drug may be, for example, a hygroscopic drug or a drug of low aqueous solubility). In a further aspect, the present invention provides a method for decreasing the hygroscopicity of a drug, which method comprises
(a) contacting the drug with propylene glycol in solution; (b) crystallizing a propylene glycol solvate of the drug from the solution; and (c) isolating the solvate, wherein the solvate has decreased hygroscopicity as compared to the drug. In a further aspect, the present invention provides a method for increasing the aqueous solubility of a drug, which method comprises
(a) contacting the drug with propylene glycol in solution; (b) crystallizing a propylene glycol solvate of the drug from the solution; and (c) isolating the solvate, wherein the solvate has increased aqueous solubility as compared to the drug. Typically, conditions for making a solvate are the same as for preparing the corresponding non-solvated form of the drug: the solvate of neutral compound would not be pH controlled; the solvate of an acid addition salt would be prepared by including PG with the drug and the acid; and the solvate of a base addition salt would involve adding the drug, the desired base, and the PG. Different co-solvent systems, anti-solvents, or temperature conditions may be used to encourage PG solvate formation. Seed crystals may be added if they have previously been prepared and isolated.
An aspect of the present invention provides a pharmaceutical composition comprising a propylene glycol solvate of a drug that is less hygroscopic than the amorphorous, neutral crystalline, or salt crystalline form, and/or has greater aqueous solubility. Hygroscopicity should be assessed by dynamic vapor sorption analysis, in which 5-50 mg of the compound is suspended from a Cahn microbalance. The compound being analyzed should be placed in a non-hygroscopic pan and its weight should be measured relative to an empty pan composed of identical material and having nearly identical size, shape, and weight. Ideally, platinum pans should be used. The pans should be suspended in a chamber through which a gas, such as air or nitrogen, having a controlled and known percent relative humidity (% RH) is flowed until eqilibrium criteria are met. Typical equilibrium criteria include weight changes of less than 0.01% change over 3 minutes at constant humidity and temperature. The relative humidity should be measured for samples dried under dry nitrogen to constant weight (<0.01% change in 3 minutes) at 40 degrees C. unless doing so would de-solvate or otherwise convert the material to an amorphous compound. In one aspect, the hygroscopicity of a dried compound can be assessed by increasing the RH from 5 to 95% in increments of 5% RH and then decreasing the RH from 95 to 5% in 5% increments to generate a moisture sorption isotherm. The sample weight should be allowed to equilibrate between each change in % RH. If the compound deliquesces or becomes amorphous between above 75% RH, but below 95% RH, the experiment should be repeated with a fresh sample and the relative humidity range for the cycling should be narrowed to 5-75% RH or 10-75% RH instead of 5-95% RH. If the sample cannot be dried prior to testing due to lack of form stability, than the sample should be studied using two complete humidity cycles of either 10-75% RH or 5-95% RH, and the results of the second cycle should be used if there is significant weight loss at the end of the first cycle.
Class 1: Non-hygroscopic
Essentially no moisture increases occur
at relative humidities below 90%.
Class 2: Slightly hygroscopic
at relative humidities below 80%.
Class 3: Moderately hygroscopic
Moisture content does not increase more
than 5% after storage for 1 week at
relative humidities below 60%.
Class 4: Very hygroscopic
Moisture content increase may occur at
relative humidities as low as 40 to 50%.
Slightly hygroscopic: Increase in mass is less than 2 percent m/m and equal to or greater than 0.2 percent m/m. Hygroscopic: Increase in mass is less than 15 percent m/m and equal to or greater than 0.2 percent m/m. Very hygroscopic: Increase in mass is equal to or greater than 15 percent m/m. Deliquescent: Sufficient water is absorbed to form a liquid. PG solvates of the present invention can be set forth as being in Class 1, Class 2, or Class 3, or as being Slightly hygroscopic, Hygroscopic, or Very hygroscopic. PG solvates of the present invention can also be set forth based on their ability to reduce hygroscopicity. Thus, preferred PG solvates of the present invention are less hygroscopic than the non-PG solvated reference compound, e.g., the reference compound of a celecoxib sodium salt PG solvate is celecoxib sodium salt. Further included in the present invention are PG solvates that do not gain or lose more than 1.0% weight at 25 degrees C. when cycled between 10 and 75% RH, wherein the reference compound gains or loses more than 1.0% weight under the same conditions. Further included in the present invention are PG solvates that do not gain or lose more than 0.5% weight at 25 degrees C. when cycled between 10 and 75% RH, wherein the reference compound gains or loses more than 0.5% or more than 1.0% weight under the same conditions. Further included in the present invention are PG solvates that do not gain or lose more than 1.0% weight at 25 degrees C. when cycled between 5 and 95% RH, wherein the reference compound gains or loses more than 1.0% weight under the same conditions. Further included in the present invention are PG solvates that do not gain or lose more than 0.5% weight at 25 degrees C. when cycled between 5 and 95% RH, wherein the reference compound gains or loses more than 0.5% or more than 1.0% weight under the same conditions. Further included in the present invention are PG solvates that do not gain or lose more than 0.25% weight at 25 degrees C. when cycled between 5 and 95% RH, wherein the reference compound gains or loses more than 0.5% or more than 1.0% weight under the same conditions.
Dissolution rate=K S(C s −C) (1)
Examples of the above embodiments include: compositions with a time to Tmax that is reduced by at least 10% as compared to the neutral free form, compositions with a time to Tmax that is reduced by at least 20% over the free form, compositions with a time to Tmax that is reduced by at least 40% over the free form, compositions with a time to Tmax that is reduced by at least 50% over the free form, compositions with a Tmax that is reduced by at least 60% over the free form, compositions with a Tmax that is reduced by at least 70% over the free form, compositions with a Tmax that is reduced by at least 80% over the free form, compositions with a Cmax that is increased by at least 20% over the free form, compositions with a Cmax that is increased by at least 30% over the free form, compositions with a Cmax that is increased by at least 40% over the free form, compositions with a Cmax that is increased by at least 50% over the free form, compositions with a Cmax that is increased by at least 60% over the free form, compositions with a Cmax that is increased by at least 70% over the free form, compositions with a Cmax that is increased by at least 80% over the free form, compositions with a Cmax that is increased by at least 2 times the free form, compositions with a Cmax that is increased by at least 3 times the free form, compositions with a Cmax that is increased by at least 4 times the free form, compositions with a Cmax that is increased by at least 5 times the free form, compositions with a Cmax that is increased by at least 6 times the free form, compositions with a Cmax that is increased by at least 7 times the free form, compositions with a Cmax that is increased by at least 8 times the free form, compositions with a Cmax that is increased by at least 9 times the free form, compositions with a Cmax that is increased by at least 10 times the free form, compositions with an AUC that is increased by at least 10% over the free form, compositions with an AUC that is increased by at least 20% over the free form, compositions with an AUC that is increased by at least 30% over the free form, compositions with an AUC that is increased by at least 40% over the free form, compositions with an AUC that is increased by at least 50% over the free form, compositions with an AUC that is increased by at least 60% over the free form, compositions with an AUC that is increased by at least 70% over the free form, compositions with an AUC that is increased by at least 80% over the free form, compositions with an AUC that is increased by at least 1 times the free form, compositions with an AUC that is increased by at least 2 times the free form, compositions with an AUC that is increased by at least 3 times the free form, or compositions with an AUC that is increased by at least 4 times the free form.
A variety of known controlled- or extended-release dosage forms, formulations, and devices can be adapted for use with the PG solvates of the present invention. Examples include, but are not limited to, those described in U.S. Pat. Nos. 3,845,770; 3,916,899; 3,536,809; 3,598,123; 4,008,719; 5,674,533; 5,059,595; 5,591,767; 5,120,548; 5,073,543; 5,639,476; 5,354,556; 5,733,566; and 6,365,185 B1; each of which is incorporated herein by reference. These dosage forms can be used to provide slow or controlled-release of one or more active ingredients using, for example, hydroxypropylmethyl cellulose, other polymer matrices, gels, permeable membranes, osmotic systems (such as OROS� (Alza Corporation, Mountain View, Calif. USA)), multilayer coatings, microparticles, liposomes, or microspheres or a combination thereof to provide the desired release profile in varying proportions. Additionally, ion exchange materials can be used to prepare immobilized, adsorbed salt forms and thus effect controlled delivery of the drug. Examples of specific anion exchangers include, but are not limited to, Duolite� A568 and Duolite� AP143 (Rohm & Haas, Spring House, Pa. USA).
A particular and well-known osmotic drug delivery system is referred to as OROS� (Alza Corporation, Mountain View, Calif. USA). This technology can readily be adapted for the delivery of compounds and compositions of the invention. Various aspects of the technology are disclosed in U.S. Pat. Nos. 6,375,978 B1; 6,368,626 B1; 6,342,249 B1; 6,333,050 B2; 6,287,295 B1; 6,283,953 B1; 6,270,787 B1; 6,245,357 B1; and 6,132,420; each of which is incorporated herein by reference. Specific adaptations of OROS� that can be used to administer compounds and compositions of the invention include, but are not limited to, the OROS� Push-Pull™, Delayed Push-Pull™, Multi-Layer Push-Pull™, and Push-Stick™ Systems, all of which are well known. See, e.g., http://www.alza.com.
Additional OROS� systems that can be used for the controlled oral delivery of compounds and compositions of the invention include OROS�-CT and L-OROS�. Id.; see also, Delivery Times, vol. II, issue II (Alza Corporation).
Non-limiting examples of suitable acids as components of effervescent agents and/or solid organic acids useful in the invention include citric acid, tartaric acid (as D-, L-, or D/L-tartaric acid), malic acid, maleic acid, fumaric acid, adipic acid, succinic acid, acid anhydrides of such acids, acid salts of such acids, and mixtures thereof. Citric acid is a preferred acid.
In an alternative embodiment, solid dosage forms are prepared by a process that includes a spray drying step, wherein a celecoxib salt is suspended with one or more excipients in one or more sprayable liquids, preferably a non-protic (e.g., non-aqueous or nonalcoholic) sprayable liquid, and then is rapidly spray dried over a current of warm air.
All powder x-ray diffraction patterns were obtained using the D/Max Rapid X-ray Diffractometer (D/Max Rapid, Contact Rigaku/MSC, 9009 New Trails Drive, The Woodlands, Tex., USA 77381-5209) equipped with a copper source (Cu/Kα 1.5406 Å), manual x-y stage, and 0.3 mm collimator, unless otherwise indicated. The sample was loaded into a 0.3 mm boron rich glass capillary tube (e.g., Charles Supper Company, 15 Tech Circle, Natick Mass. 01760-1024) by sectioning off one end of the tube and tapping the open, sectioned end into a bed of the powdered sample or into the sediment of a slurried precipitate. Note, precipitate can be amorphous or crystalline. The loaded capillary was mounted in a holder that was secured into the x-y stage. A diffractogram was acquired (e.g., Control software: RINT Rapid Control Software, Rigaku Rapid/XRD, version 1.0.0, � 1999 Rigaku Co.) under ambient conditions at a power setting of 46 kV at 40 mA in reflection mode, while oscillating about the omega-axis from 0-5 degrees at 1 degree/s and spinning about the phi-axis at 2 degrees/s. The exposure time was 15 minutes unless otherwise specified. The diffractogram obtained was integrated over 2-theta from 2-60 degrees and chi (1 segment) from 0-360 degrees at a step size of 0.02 degrees using the cyllnt utility in the RINT Rapid display software (Analysis software: RINT Rapid display software, version 1.18, Rigaku/MSC.) provided by Rigaku with the instrument. The dark counts value was set to 8 as per the system calibration (System set-up and calibration by Rigaku); normalization was set to average; the omega offset was set to 180�; and no chi or phi offsets were used for the integration. The analysis software JADE XRD Pattern Processing, versions 5.0 and 6.0 ((81995-2002, Materials Data, Inc. was also used.
An aliquot of the sample was weighed into an aluminum sample pan. (e.g., Pan part # 900786.091; lid part # 900779.901; TA Instruments, 109 Lukens Drive, New Castle, Del. 19720) The sample pan was sealed either by crimping for dry samples or press fitting for wet samples (e.g., hydrated or solvated samples). The sample pan was loaded in to the apparatus (DSC: Q1000 Differential Scanning Calorimeter, TA Instruments, 109 Lukens Drive, New Castle, Del. 19720), which is equipped with an autosampler, and a thermogram was obtained by individually heating the sample (e.g., Control software: Advantage for QW-Series, version 1.0.0.78, Thermal Advantage Release 2.0, � 2001 TA instruments-Water LLC) at a rate of 10 degrees C./min from Tmin (typically 20 degrees C.) to Tmax (typically 300 degrees C.) (Heating rate and temperature range may vary, changes to these parameters will be indicated for each sample) using an empty aluminum pan as a reference. Dry nitrogen (e.g., Compressed nitrogen, grade 4.8, BOC Gases, 575 Mountain Avenue, Murray Hill, N.J. 07974-2082) was used as a sample purge gas and was set at a flow rate of 50 mL/min. Thermal transitions were viewed and analyzed using the analysis software (Analysis Software: Universal Analysis 2000 for Windows 95/95/2000/NT, version 3.1E; Build 3.1.0.40, � 1991-2001TA instruments-Water LLC) provided with the instrument.
An aliquot of the sample was transferred into a platinum sample pan. (Pan part # 952019.906; TA Instruments, 109 Lukens Drive, New Castle, Del. 19720) The pan was placed on the loading platform and was then automatically loaded in to the apparatus (TGA: Q500 Thermogravimetric Analyzer, TA Instruments, 109 Lukens Drive, New Castle, Del. 19720) using the control software (Control software: Advantage for QW-Series, version 1.0.0.78, Thermal Advantage Release 2.0, (D 2001 TA instruments-Water LLC). Thermograms were obtained by individually heating the sample at 10 degrees C./min from 25 degrees C. to 300 degrees C. (Heating rate and temperature range may vary, changes in parameters will be indicated for each sample) under flowing dry nitrogen (e.g., Compressed nitrogen, grade 4.8, BOC Gases, 575 Mountain Avenue, Murray Hill, N.J. 07974-2082), with a sample purge flow rate of 60 mL/min and a balance purge flow rate of 40 mL/min. Thermal transitions (e.g. weight changes) were viewed and analyzed using the analysis software (Analysis Software: Universal Analysis 2000 for Windows 95/95/2000/NT, version 3.1E; Build 3.1.0.40, � 1991-2001TA instruments-Water LLC) provided with the instrument.
A propylene gly solvate of the lithium salt of celecoxib was prepared. To a solution of celecoxib (264 mg, 0.693 mmol) in diethyl ether (8 mL) was added propylene glycol (0.075 mL, 1.02 mmol). To the clear solution was added t-butyl lithium in pentane (1.7 M, 0.40 mL, 0.68 mmol). A brown solid formed immediately but dissolved within one minute which subsequently yielded a white fluffy solid. The white solid crystallized completely after 10 minutes. The solid was collected by filtration and was washed with additional diethyl ether (10 mL). The white solid was then air-dried and collected. The crystalline salt form was found to be a 1:1 propylene glycol solvate of celecoxib Li. The solid was characterized by TGA and PXRD.
A propylene glycol solvate of a sodium salt of naproxen was prepared. To a solution of naproxen (348 mg, 1.51 mmol) in diethyl ether (10 mL) was added propylene glycol (0.200 ml, 2.72 mmol). To the clear solution was added sodium ethoxide in ethanol (21%, 0.750 mL, 2.01 mmol). The solution became slightly yellow due to the sodium ethoxide. After 1 minute, crystals began to form. After 5 minutes, the solid had completely crystallized. The solid was collected by filtration and was washed with diethyl ether (10 mL). The product was then air-dried and collected. The solvate was 2:1 naproxen Na:propylene glycol. The solid was characterized by TGA and PXRD. The TGA thermogram of naproxen sodium salt PG solvate is shown in FIG. 7, and indicates a 13.5 percent weight loss between about 75 and 150 degrees C. This weight loss is consistent with a 2:1 naproxen Na:propylene glycol solvate. The PXRD diffractogram of naproxen sodium salt PG solvate is shown in FIG. 8, and shows peaks at 2-theta angles, including but not limited to, 6.67, 9.65, 13.41, 15.77, 18.55, 20.83, 22.79, and 27.17 degrees. Any one, any two, any three, any four, any five, any six, any seven, or all eight of the above peaks or any one or any combination of peaks in FIG. 8 can be used to characterize naproxen sodium salt PG solvate.
Results from TGA analysis show a 15.9% weight loss at temperatures up to 150 degrees C. (FIG. 13). 14.9% weight loss occured between 70 and 150 degrees C. while up to 1.2% weight loss occurred at lower temperatures. This weight loss is representative of a cortisone acetate PG solvate with 1.0 equivalents of propylene glycol. DSC was completed in a closed, not sealed aluminium pan from room temperature to 300 degrees C. at 10 degrees/minute (FIG. 14). The compound was discovered to have two endothermic transitions, one at 148 degrees C. with an intensity of 146 J/g, and the second at 237 degrees C. with an intensity of 77 J/g.
Single-crystal x-ray studies of cortisone acetate PG solvate were also completed.
FIG. 17 shows a packing diagram of the single-crystal structure of cortisone acetate PG solvate. The unit cell data are as follows: space group P2(1), A=9.728(2), B=7.6306(15), C=16.454(3), Alpha=90, Beta=92.568(4), Gamma=90, Volume=1220.2(4).
API Generic Name
API Chemical Name
(−)-amlodipine
3,5-Pyridinedicarboxylic acid, 2-((2-
Antihypertensive, other
Hypertension, aminoethoxy)methyl)-4-(2-
chlorophenyl)-1,4-dihydro-6-methyl-,
3-ethyl-S-methyl ester, (S)-[CAS]
(−)-halofenate
(−)-Benzeneacetic acid, 4-chloro-Alpha-
6,262,118
[3-(trifluoromethyl)-phenoxy]-, 2-
(acetylamino)ethyl ester
1,3-Benzenedimethanol, Alpha1-(((1,1-
Formulation, modified-
dimithylethyl)amino)methyl)-4-hydroxy-
release, <=24 hr
5,547,994
dimethylethyl)amino)methyl)-4-hydroxy-
Formamide, N-(2-hydroxy-5-(1-hydroxy-
5,795,564
2-((2-(4-methoxyphenyl)-1-
methylethyl)amino)ethyl)phenyl)- (R-
(R*,R*))-[CAS]
(S)-doxazosin
(S)-1-(4-amino-6,7-dimethoxy-2-
70918-18-2
9409785
Benign prostatic quinazolinyl)-4-(1,4-benzodioxan-2-yl
carbonyl)piperazine
(S)-fluoxetine
Benzenepropanamide, N-methyl-
Gamma-(4-(trifluoromethyl)phenoxy)-
Benzeneacetic acid, Alpha-cyclohexyl-
119618-22-3
Alpha-hydroxy-, 4-(diethylamino)-2-
butynyl ester, (S)-[CAS]
1,2-Naphtho-
gesterone
17-Methyl-
Platinum-195m, diamminedichloro, (SP-
6,074,626
Anticancer, alkylating
4-2)-
1a-Hydroxy-
1-Naphthyl 550-97-0
amine-4-
1-Theobromine- 5614-56-2
2,4,6-Tribromo-m-
2,6-Diamino-2�-
617-19-6
butyloxy-3,5�-
21-Acetoxy-
566-78-9
2-Amino-4-
2-ethoxybenzoic 2-Ethoxybenzoic acid
Analgesic, NSAID
2-Naphthyl 93-44-7
2-Naphthyl 93-43-6
2-Naphthyl 613-78-5
2-p-
80-02-4
Sulfanilyl-
anilinoethanol
3�,3��,5�,5��-
Tetrabromophenol-
3-Amino-4-
589-44-6
3-Bromo-d-
10373-81-6
1562-13-6
Lauroylpyridoxol
492-89-7
Pentadecyl-
3-Quinuclidinol
4,4�-Oxydi-2-
821-33-0
4,4�-
Sulfinyldianiline
4-Amino-3-
4-aminosali-
GI inflammatory/bowel inflammatory cylic acid
4-Chloro-m-
Hexytresorcinol
3202-84-4
Salicyloyl-
5�-Nitro-2�-
553-20-8
5-aminolevulinic Pentanoic acid, 5-amino-4-oxo-[CAS]
1,3,5-Triazin-2(1H)-one, 4-amino-1-β-
Anticancer, Mylodysplastic D-ribofuranosyl-[CAS]
5798-94-7
Bromosalicyl-
5F-DF-203
2-(4-Amino-3-methylphenyl)-6-
Anticancer, other
2,4(1H,3H)-Pyrimidinedione, 5-fluoro
Formulation, parenteral, Cancer, general
5-HT3 U.S.
6,037,360
6-Mercapto-
91421-43-1
A-151892
N-[2-(2,2,2-Trifluoro-1-hydroxy-1-
trifluoromethyl-ethyl)-naphthalen-1-yl]
A-5021
6H-Purin-6-one, 2-amino-9-(((1S,2R)-
145512-85-2
Infection, varicella 1,2-
bis(hydroxymethyl)cyclopropyl)methyl)-
1,9-dihydro-[CAS]
2-Cyclopentene-1-methanol, 4-(2-
Antiviral, anti-HIV
Infection, HIV/AIDS
amino-6-(cyclopropylamino)-9H-purin-9-
yl)-, (1S-cis)-[CAS]
7-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-
183849-43-6
yl)piperidin-1-yl]propoxy]-3-
(hydroxymethyl)chromen-4-one
D-Alaninamide, N-acetyl-3-(2-
5,843,902
Anticancer, hormonal
naphthalenyl)-D-alanyl-4-chloro-D-
phenylalanyl-3-(3-pyridinyl)-D-alanyl-L-
seryl-N-methyl-L-tyrosyl-D-asparaginyl-
L-leucyl-N6-(1-methylethyl)-L-lysyl-L-
prolyl-[CAS]
111841-85-1
169147-32-4
5,552,391
Androsta-5,16-dien-3-ol, 17-(3-
pyridinyl)-, acetate (ester), (3β)-[CAS]
Amphotericin B [CAS]
Formulation, conjugate,
Infection, Candida, 30652-87-0
Benzenesulfonamide, N-[2-[(4-
141430-65-1
hydroxyphenyl)amino]-3-pyridinyl]-4-
methoxy-[CAS]
AC-5216
N-benzyl-N-ethyl-2-(7,8-dihydro-7-
methyl-8-oxo-2-phenyl-9H-purin-9-
1-Propanesulfonic acid, 3-
(acetylamino)-[CAS]
7H-Purine-7-acetic acid, 1,2,3,6-
tetrahydro-1,3-dimethyl-2,6-dioxo-,
compd. with trans-4-[[(2-amino-3,5-
dibromophenyl)methyl]amino]cyclo-
hexanol (1:1) [CAS]
Butanamide, N-[3-acetyl-4-[2-hydroxy-3-
3,726,919
Antihypertensive, [(1-methylethyl)amino]propoxy]phenyl]-,
(+/−)-[CAS]
32795-44-1
Benzeneacetic acid, 2[(2,6-
dichlorophenyl)amino]-, carboxymethyl
ester [CAS]
Aluminum, pentakis(N2-acetyl-L-
Ulcer, GI, general
glutaminato)tetrahydroxytri-[CAS]
1H-Indole-3-acetic acid, 1-(4-
3,910,952
chlorobenzoyl)-5-methoxy-2-methyl-,
carboxymethyl ester [CAS]
Acetamido-
Acetohydroxamic 546-88-3
2751-68-0
128-12-1
Olean-12-en-30-oic acid, 3β-hydroxy-
29728-34-5
3,764,618
11-oxo-acetate, aluminium salt [CAS]
Acetyl 3590-05-4
Sulfamethoxy-
14992-62-2
149-90-6
acetylsalicylic Benzoic acid, 2-(acetyloxy)-[CAS]
Formulation, optimized,
6H-Purin-6-one, 2-amino-1,9-dihydro-9-
Formulation, dermal, Infection, herpes [(2-hydroxyethoxy)methyl]-[CAS]
Pyrazinecarboxylic acid, 5-methyl-, 4-
1361967
Hypolipaemic/
Hyperlipidaemia, oxide [CAS]
Acetic acid, oxo[[3-(1H-tetrazol-5-
114607-46-4
yl)phenyl]amino]-[CAS]
2,4,6,8-Nonatetraenoic acid, 9-(4-
methoxy-2,3,6-trimethylphenyl)-3,7-
dimethyl-, (all-E)-[CAS]
3,988,315
Anticancer, antibiotic
Aclatonium 55077-30-0
Acranil �
1684-42-0
7527-91-5
2-Propenoic acid, 3-[6-[1-(4-
Antipruritic/inflamm, Rhinitis, allergic, methylphenyl)-3-(1-pyrrolidinyl)-1-
propenyl]-2-pyridinyl]-, (E,E)-[CAS]
acrivastine +
Benzenemethanol, Alpha-[1-
Antiallergic, non-asthma
Rhinitis, allergic, pseudo-
(methylamino)ethyl]-, hydrochloride, [S-
(R*,R)]-, mixtwith 2-Propenoic acid, 3-
[6-[1-(4-methylphenyl)-3-(1-pyrrolidinyl)-
1-propenyl]-2-pyridinyl]-, (E,E)-
actagardine 3,3-dimethyl-1-propylamide HCl
Infection, general
monocarboxamide actagardine
2-Naphthalenecarboxylic acid, 6-(4-
methoxy-3-tricyclo[3.3.1.13,7]dec-1-
ylphenyl)-[CAS]
GL 402 [CAS]
137802-74-5
Formulation, other
Fibrosis, epidural
adefovir Propanoic acid, 2,2-dimethyl-, (((2-(-6-
Infection, hepatitis-B dipivoxil
amino-9H-purin-9-
yl)ethoxy)methyl)phosphinyl
idene)bis(oxymethylene)ester-[CAS]
6-Amino-9-β-D-nbofuranosyl-9H-purine
Diagnosis, coronary
Adenosine 56-65-5
156079-88-8
Immunoconjugate, other
37115-32-5
ADL-10-0101
9732857
Analgesic, other
Benzo(f)thieno(2,3-c)quinoline-9,10-
166591-11-3
diol, 4,5,5a,6,7,11b-hexahydro-2-propyl-,
171752-56-0
diacetate (ester), hydrochloride (5aR-
trans)-[CAS]
AEOL-10150
6,103,714
a-Ethylbenzyl 93-54-9
AF-2259
Benzeneacetic acid, Alpha-methyl-4-(2-
66332-77-2
2726435
Inflammation, general
methylpropyl)-, 2-methoxyphenyl ester
1H-Indole-3-acetamide, 1-(2,2-
199800-49-2
9419322
Alimentary/Metabolic, Unspecified
diethoxyethyl)-2,3-dihydro-N-(4-
methylphenyl)-3-((((4-
methylphenyl)amino)carbonyl)amino)-2-
oxo-, (3R)-[CAS]
AG-2037
N-(5-[2-(2-amino-4(3H)-oxo-5,6,7,8-
Anticancer, Cancer, general
tetrahydropyrido[2,3-d]pyrimidin-6-
yl)ethy]-4-methylthieno-2-yl)glutamic
a-Glucose-1-
AGN-194310
Benzoic acid, 4-((4-(4-ethylphenyl)-2,2-
9709297
dimethyl-2H-1-benzothiopyran-6-
yl)ethynyl)-[CAS]
Acetamide, N-(2-(7-methoxy-1-
Sleep disorder, naphthalenyl)ethyl)-[CAS]
AHL-157
5,411,972
9H-Purine-9-propanamide, 1,6-dihydro-
138117-48-3
5,447,939
Dementia, senile, 6-oxo-N-(3-(2-oxo-1-pyrrolidinyl)propyl)-
AIT-202
N-(2-(5-Hydroxy-1H-indol-3-yl)ethyl]-3-
9957120
(6-oxo-6,9-dihydro-1H-purin-9-
AJ-9677
Acetic acid, ((3-((2R)-2-(((2R)-2-(3-
244081-42-3
chlorophenyl)-2-
hydroxyethyl)amino)propyl)-1H-indol-7-
yl)oxy)-[CAS]
AJG-049
Motility dysfunction, GI, general
12/07/4360
4(3H)-Quinazolinone, 7-chloro-3-
9705131
Infection, Candida, [(1R,2R)-2-(2,4-difluorophenyl)-2-
hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-
yl)propyl]-[CAS]
Carbamic acid, [5-(propylthio)-1H-
Infection, helminth, benzimidazol-2-yl]-, methyl ester [CAS]
Benzeneacetic acid, 3-chloro-4-(2-
propenyloxy)-[CAS]
Pregna-1,4-diene-3,20-dione, 7-chloro-
4,124,707
Antipruritic/inflamm, Inflammation, dermal
11-hydroxy-16-methyl-17,21-bis(1-
oxopropoxy)-, (7Alpha,11β,16Alpha)-
23214-96-2
Phosphonic acid, (4-amino-1-
hydroxybutylidene)bis-[CAS]
129318-43-0
Alendronic 66376-36-1
9,10-Secocholesta-5,7,10(19)-triene-
1,3-diol, (1Alpha,3β,5Z,7E)-[CAS]
23930-37-2
259074-76-5
2-Furancarboxamide, N-[3-[(4-amino-
Benign prostatic 6,7-dimethoxy-2-
quinazolinyl)methylamino]propyl]tetra-
hydro-[CAS]
Formulation, modivied-
release, other
Algestone 24356-94-3
Acetophenide
143003-46-7
26750-81-2
(2S,4S,5S,7S)-5-Amino-N-(2-
Antihypertensive, renin Hypertension, general
carbamoyl-2-methylpropyl)-4-hydroxy-2-
isopropyl-7-[4-methoxy-3-(3-
methoxypropoxy)benzyl]-8-
methylnonanamide
03/08/5300
Antipruritic/inflamm, Eczema, general
1H-Benzotriazoie-5-carboxamide, 6-
59338-93-1
methoxy-N-[[1-(2-propenyl)-2-
vomiting, general
pyrrolidinyl)methyl]-[CAS]
7527-94-8
Allyl 57-06-7
Magnesium, [carbon-
4,447,417
Antacid/Antiflatulent
ato(2-)]heptahydroxy(aluminum)tri-,
72526-11-5
dihydrate [CAS]
Benzeneacetic acid, Alpha-methyl-4-[(2-
39718-89-3
methyl-2-propenyl)amino]-[CAS]
1,3,5-Triazine-2,4-diamine, 6-[4-[bis(4-
27469-53-0
fluorophenyl)methyl]-1-piperazinyl]-N,N′
di-2-propenyl-, dimethanesulfonate
Pyrrolidine, 1-(((3-(2-
9402460
(dimethylamino)ethyl)-1H-indol-5-
yl)methyl)sulfonyl)-[CAS]
2,3,4,5-Tetrahydro-5-methyl-2-[(5-
GI inflammatory/bowel Irritable bowel methyl-1H-imidazol-4-yl)methyl]-1H-
pyrido[4,3-b]indol-1-one [CAS]
132414-02-9
Thymidine, 3′-deoxy-3′-fluoro-[CAS]
9014-67-9
Alpha-1 U.S.
5,780,014
Formulation, inhalable, Emphysema, alpha-1
Ergocryptine, 9,10-dihydro-
29261-93-6
dihydroer-
methanesulfonate (salt)-[CAS]
gocryptine
81982-32-3
4H-[1,2,4]Triazolo[4,3-
3,987,052
al][1,4]benzodiazepine, 8-chloro-1-
methyl-6-phenyl-[CAS]
Alpha1-17-Corticotropin, 1-β-alanine-
34765-96-3
3,749,704
17-[N-(4-aminobutyl)-L-lysinamide]-
Thiazolium, 4,5-dimethyl-3-(2-oxo-2-
181069-80-7
Symptomatic Hypertension, general
phenylethyl)-, bromide [CAS]
Pyridine, 3-ethynyl-5-((2S)-1-methyl-2-
179120-92-4
pyrrolidinyl)-[CAS]
1,3,5-Triazine-2,4,6-triamine,
3,424,752
N,N,N′,N′,N″,N″-hexamethyl-[CAS]
aluminium Aluminium chloride, hexahydrate
Aluminum 8006-13-1
Aluminum 15477-33-5
Aluminum 1327-41-9
Aluminum 10043-67-1
Aluminum 10102-71-3
Aluminum hydroxide sulfate
(Al7(OH)17(SO4)2), dodecahydrate
Glycine, N-[(2S)-2-[[(3R,4R)-4-(3-
GI inflammatory/bowel Ileus
hydroxyphenyl)-3,4-dimethyl-1-
piperidinyl]methyl]-1-oxo-3-
phenylpropyl]-[CAS]
4H-1-Benzopyran-4-one, 2-(2-
Cancer, renal
chlorophenyl)-5,7-dihydroxy-8-(3-
hydroxy-1-methyl-4-piperidinyl)-, cis-(−)-
ALX-0646
GI inflammatory/
1-Piperazineethanol, 4-[[3,5-bis(1,1-
199467-52-2
dimethylethyl)-4-hydroxyphenyl]methyl]-
Alpha-(4-chlorophenyl)-[CAS]
amantanium
1-Decanaminium, N,N-dimethyl-N-[2-
58158-77-3
4,288,609
[(tricyclo[3.3.1.13,7]dec-1-
ylcarbonyl)oxy]ethyl]-, bromide [CAS]
(+)-(2S)-2-[(4,6-dimethylpyrimidin-2-
Vasodilator, peripheral
yl)oxy]-3-methoxy-3,3-
diphenylpropanoic acid
Cyclohexanol, 4-[[(2-amino-3,5-
dibromophenyl)methyl]amino]-,
trans-[CAS]
119-29-9
5634-34-4
Ambuside
3754-19-6
Ambutonium 115-51-5
Pregna-1,4-diene-3,20-dione, 21-
(acetyloxy)-16,17-
[cyclopentylidenebis(oxy)]-9-fluoro-11-
hydroxy-, (11β, 16Alpha)-[CAS]
5,612,478
1,11-(1,4-phenylenebis(methylene))bis-,
induced injury,
octahydrochloride [CAS]
Amdinociiiin 32886-97-8
1,3-Dioxolane-2-methanol, 4-(2,6-
145514-04-1
diamino-9H-purin-9-yl)-(2R-cis)-[CAS]
Carbamic acid, ((4-((3-((4-(1-(4-
hydroxyphenyl)-1-
methylethyl)phenoxy)methyl)phen-
yl)methoxy)phenyl)iminomethyl)-ethyl ester [CAS]
Benzenemethanaminium, N,N-dimethyl-
129128-13-8
Formulation, inhalable, Pain, general
N-[2-[2-[4-(1,1,3,3-
tetramethylbutyl)phenoxy]ethoxy]ethyl]-,
chloride, mixt. with ethyl 4-
aminobenzoate [CAS]
51579-82-9
3354-67-4
Amidinomycin
3572-60-9
Ethanethiol, 2-[(3-aminopropyl)amino]-,
Radio/chemoprotective
dihydrogen phosphate (ester)-[CAS]
63717-27-1
induced injury, renal
amiglumide
Pentanoic acid, 5-(dipentylamino)-4-((2-
119363-62-1
8805774
naphthalenylcarbonyl)amino)-5-oxo-
(R)-[CAS]
Heptanoic acid, 7-[(10,11-dihydro-5H-
3,758,528
dibenzo[a,d]cyclohepten-5-yl)amino]-
2,6-Piperidinedione, 3-(4-aminophenyl)-
3,944,671
3-ethyl-[CAS]
642-44-4
1H-Purine-2,6-dione, 3,7-dihydro-1,3-
dimethyl-, compd. with 1,2-
ethanediamine (2:1) [CAS]
3811-56-1
Methanone, (2-butyl-3-benzofuranyl)[4-
3,248,401
Arrhythmia, general
[2-(diethylamino)ethoxy]-3,5-
diiodophenyl]-[CAS]
490-55-1
56824-20-5
Benzamide, 4-amino-N-[(1-ethyl-2-
4,401,822
pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-
amitriptyline + 1-Propanamine,3-(10,11-dihydro-5H-
Formulation, fixed-dose
dibenzo[a,d]cyclohepten-5-ylidene)-
N,N-dimethyl + cyclohexanone,2-(2-
chlorophenyl)-2-(methylamino)
Amitriptylin-
4317-14-0
5H-[1]Benzopyrano[2,3-b]pyridine-3-
4,299,963
carboxylic acid, 2-amino-7-(1-
methylethyl)-5-oxo-[CAS]
3,5-Pyridinedicarboxylic acid, 2-[(2-
Hypertension, general
aminoethoxy)methyl]-4-(2-
chlorophenyl)-1,4-dihydro-6-methyl-, 3-
ethyl 5-methyl ester [CAS]
03/07/9000
Ammonium 1863-63-4
Ammonium 530-31-4
Ammonium 528-94-9
Ammonium 42739-38-8
36590-19-9
Morpholine, 4-[3-[4-(1,1-
Infection, fungal, dimethylpropyl)phenyl]-2-methylpropyl]-
2,6-dimethyl-, cis-[CAS]
26328-53-0
Benzenesulfonamide, 5-[1-hydroxy-2-
70958-86-0
Antihypertensive, Hypertension, general
[[2-(2-
85320-68-9
methoxyphenoxy)ethyl]amino]ethyl]-2-
methyl-, (+/−)-[CAS]
Amotriphene
5585-64-8
Dibenz[b,f][1,4]oxazepine, 2-chloro-11-
(1-piperazinyl)-[CAS]
4-Thia-1-azobicyclo[3,2,0]heptane-2-
carboxylic acid, 6-[[amino(4-
hydroxyphenyl)acetyl]amino]-3,3-
dimethyl-7-oxo-,[2S-
[2Alpha,5Alpha,6β(S*)]] [CAS]
amoxicillin + 74469-00-4
Infection, respiratory potassium combinations
tract, general
Piperidine, 1-(6-quinoxalinylcarbonyl)-
5,650,409
Attention deficit [CAS]
amphotericin Amphotericin B compd. with (3β)-
120895-52-5
4,822,777
Formulation, optimized, Infection, general
cholest-5-en-3-yl hydrogen sulfate (1:1)
4-Thia-1-azabicyclo[3.2.0]heptane-2-
carboxylic acid, 6-
[(aminophenylacetyl)amino]-3,3-
dimethyl-7-oxo-, [2S-
[2Alpha,5Alpha,6β(S*)]]
Ampirox-
38640-92-5
Carbamic acid, (3-(((4-
5,783,701
aminophenyl)sulfonyl)(2-
methylpropyl)amino)-2-hydroxy-1-
(phenylmethyl)propyl)-, tetrahydro-3-
furanyl ester, (3S-(3R*(1R*,2S*)))-
[3,4′-Bipyridin]-6(1H)-one, 5-amino-
4,004,012
75898-90-7
5,12-Naphthacenedione, 9-acetyl-9-
Cancer, lung, amino-7-[(2-deoxy-β-D-erythro-
pentopyranosyl)oxy]-7,8,9,10-
tetrahydro-6,11-dihydroxy-,
hydrochloride, (7S-cis)-[CAS]
Methanesulfonamide, N-(4-(9-
Cancer, leukaemia, acridinylamino)-3-methoxyphenyl]-
amtolmetin Glycine, N-[[1-methyl-5-(4-
methylbenzoyl)-1H-pyrrol-2-yl]acetyl]-,
2-methoxyphenyl ester [CAS]
9719954
anabolic WO
2740-52-5
Imidazo[2,1-b]quinazolin-2(3H)-one,
6,7-dichloro-1,5-dihydro-,
monohydrochloride [CAS]
1,3-Benzenediacetonitrile,
Alpha,Alpha,Alpha,Alpha′-tetramethyl-5-
(1H-1,2,4-triazol-1-ylmethyl)-[CAS]
andolast
N-4′-[5-Tetrazolyl]-phenyl-4-(5-
132640-22-3
tetrazolyl)-benzamide
360-66-7
21-(Acetyloxy)-17-hydroxypregna-
Macular 4,9(11)-diene-3,20-dione
4180-23-8;
Anethole 532-11-6
Trithione
6,417,205
Cardiomyopathy, ischaemic
1407-47-2
Vincaleukoblastine, 3′,4′-didehydro-4′-
6,011,041
deoxy-[CAS]
Echinocandin B, 1-((4R,5R)-4,5-
6,384,013
Infection, Candida, dihydroxy-N2-((4″-(pentyloxy)(1,1′:4′,1″-
terphenyl)-4-yl)carbonyl)-L-ornithine)-
Anisotropine 80-50-2
Anistreplase [CAS]
81669-57-0
Anthiolimine
305-97-5
4803-27-4
577-33-3
anthrax U.S.
6,436,933
Anti-infective, other
Infection, anthrax
antiangiogenic U.S.
6,426,067
L-Ascorbic acid, mixt with 2-
186646-39-9
9640038
(diethylamino)ethyl 4-aminobenzoate
monohydrochloride, disodium
benzoate and zinc sulfate (1:1) [CAS]
5,898,036
anti-invasins
6,303,302
Infection, fungal, general
Antimony 28300-74-5
Antimony 539-54-8
Antimony 6533-78-4
Thioglycoll-
19-Norpregna-4,9-dien-3-
19706061
one,(acetylphenyl)-20,20,21,21,21-
pentafluoro-17-hydroxy-(11β,17Alpha)
Antipyrine 520-07-0
Antithrombin, III [CAS]
Antithrombin III 90170-80-2
5,756,538
N-Piperonyl-2-amino-1,2,3,4-
151227-08-6
9321189
tetrahydrobenzo(b)thieno(2,3-
c)pyridine-3-carbamide
AP-5280
5,965,118
63469-19-2
1H-Indole-4,7-dione, 5-(1-aziridinyl)-3-
(hydroxymethyl)-2-(3-hydroxy-1-
propenyl)-1-methyl-, (E)-[CAS]
13539-59-8
a-Phenyl-
641-36-1
Phosphonic acid, (2-(3,5-bis(1,1-
126411-13-0
dimethylethyl)-4-
hydroxyphenyl)ethylidene)bis-
tetrakis(1-methylethyl) ester [CAS]
4H-Dibenzo[de,g]quinoline-10,11-diol,
314-19-2
Formulation, Impotence
5,6,6a,7-tetrahydro-6-methyl-,
transmucosal, hydrochloride
1,4-Benzenediamine, 2,6-dichloro-N1-
4,517,199
(4,5-dihydro-1H-imidazol-2-yl)-[CAS]
3H-1,2,4-Triazol-3-one, 5-[[(2R,35)-2-
5,719,147
[(1R)-1-[3,5-
induced nausea bis(trifluoromethyl)phenyl]ethoxy]-3-(4-
fluorophenyl)-4-morpholinyl]methyl]-1,2-
dihydro-[CAS]
1,3-Propanediamine, N-(2,3-dihydro-
1H-inden-2-yl)-N′,N′-diethyl-N-phenyl-
37640-71-4
137159-92-3
9,10-Anthracenedione, 1,4-bis((2-
136470-65-0
5,132,327
(dimethyloxidoamino)ethyl)amino)-5,8-
dihydroxy-[CAS]
6,204,257
Anaesthetic, injectable
AR-116081
6,107,324
AR-A2
(R)-N-[5-methyl-8-(4-methylpiperazin-1-
yl)-1,2,3,4-tetrahydro-2-naphthyl]-4-
morpholinobenzamide
Arachidonic 506-32-1
3,5-Pyridinedicarboxylic acid, 1,4-
2111978
dihydro-2,6-dimethyl-4-(2-nitrophenyl)-,
methyl 2-oxopropyl ester-[CAS]
D-Streptamine, O-3-amino-3-deoxy-
51025-85-5
4,001,208
Aminoglycoside Infection, general
Alpha-D-glucopyranosyl-(1-6)-O-[2,6-
75282-65-4
diamino-2,3,4,6-tetradeoxy-Alpha-D-
erythro-hexopyranosyl-(1-4)]-N1-(4-
amino-2-hydroxy-1-oxobutyl)-2-deoxy-,
(S)-[CAS]
1H-indole-3-carboxylic acid, 6-bromo-4
Immunostimulant, other
Infection, influenza ((dimethylamino)methyl)-5-hydroxy-1-
methyl-2-((phenylthio)methyl)-,
ethylester, monohydrochloride [CAS]
1,2-Benzenediol, 4-[1-hydroxy-2-[[4-(4-
128470-16-6
hydroxyphenyl)butyl]amino]ethyl]-, (R)-
154361-48-5
Heparin [CAS]
1,2,5,6-Tetrahydro-1-methyl-3-pyridine
Formulation, Alzheimer's disease
transdermal, patch
2-Piperidinecarboxylic acid, 1-[5-
Thrombosis, arterial
[(aminoiminomethyl)amino]-1-oxo-2-
[[(1,2,3,4-tetrahydro-3-methyl-8-
quinolinyl)sulfonyl]amino]pentyl]-4-
methyl-[CAS]
Ariflo �
2(1H)-Quinolinone, 7-[4-[4-(2,3-
dichlorophenyl)-1-piperazinyl]butoxy]
3,4-dihydro-[CAS]
1H-Purine-2,6-dione, 3-(4-
136145-07-8
chlorophenyl)-3,7-dihydro-1-propyl-
2-Thiophenecarboxamide, 5-[2-[[3-[(1,1-
104766-23-6
dimethylethyl)amino]-2-
68377-92-4
hydroxypropyl]thio]-4-thiazolyl]-, (�)-
618-22-4
Arsenic oxide (As2O3) [CAS]
Cancer, leukaemia, acute myelogenous
75887-54-6
Arteflene
123407-36-3
(Z-form)
3,12-Epoxy-12H-pyrano[4,3-j]-1,2-
benzodioxepin, 10-ethoxydecahydro-
3,6,9-trimethyl-, [3R-
(3Alpha,5aβ,6β,8aβ,9aAlpha,10Alpha,
12+62,12aR*)]-[CAS]
Butanedioic acid mono-
Formulation, Infection, malaria
[(3R,5aS,6R,8aS,9R,10R,12R,12aR)-
transmucosal,
decahydro-3,6,9-trimethyl-3,12-epoxy-
12H-pyrano[4,3-j]-1,2-benzodioxepin-
10-yl]ester
Benzo(b)thiophene-6-ol,2-(4-
182133-27-3
methoxyphenyl)-3-(4-(2-(1-
piperidinyl)ethoxy)phenoxy)-[CAS]
Spiro(pyrrolidine-3,4′(1′H)-pyrrolo(1,2-
Symptomatic Diabetic a)pyrazine)-1′,2,3′,5(2′H)-tetrone, 2′-((4-
bromo-2-fluorophenyl)methyl)-, (3′R)-
Benzoic acid, 2-(acetyloxy)-[CAS]
a-Santonin
Ascorbic 50-81-7
1H-Dibenz[2,3:6,7]oxepino[4,5-
Psychosis, general
c]pyrrole, 5-chloro-2,3,3a,12b-
tetrahydro-2-methyl-, trans-, (Z)-2-
butenedioate (1:1) [CAS]
Benzeneacetamide, N-[2-(3-hydroxy-1-
4215213
GI inflammatory/bowel Irritable bowel pyrrolidinyl)-1-phenylethyl]-N-methyl-
Alpha-phenyl-, [S-(R*,R*)]-[CAS]
11β-[4-(Hydroxyiminomethyl)phenyl]-
199396-76-4
0648778
17β-methoxy-17Alpha-
(methoxymethyl)estra-4,9-dien-3-one
34433-31-3
584-28-1
519-40-4
Glycinamide, N-methyl-D-asparaginyl-
Penicillin, injectable
Infection, respiratory N-(2-carboxy-3,3-dimethyl-7-oxo-4-thia-
1-azabicyclo[3.2.0]hept-6-yl)-D-2-(4-
hydroxyphenyl)-, [2S-
(2Alpha,5Alpha,6β)]-[CAS]
AST 120 [CAS]
4-Acridinecarboxamide, 9-[[2-methoxy-
80841-47-0
4-[(methylsulfonyl)amino]phenyl]amino]-
80841-48-1
N,5-dimethyl-[CAS]
(N-[2-[4-(5H-Dibenzo[a,d]cyclohepten-
Thrombosis, general
5-ylidene)-piperdino]ethyl]-1-formyl-4-
monohydrochioride monohydrate
Androsta-1,4-diene-3,17-dione, 1-
96301-34-7
3338212
2,5,6,10,13-Pentaazatetradecanedioic
acid, 3,12-bis(1,1-dimethylethyl)-8-
hydroxy-4,11-dioxo-9-(phenylmethyl)-6-
((4-(2-pyridinyl)phenyl)methyl)-
dimethyl ester, (3S,8S,9S,12S)-,
sulfate (1:1) (salt) [CAS]
Benzeneacetamide, 4-[2-hydroxy-3-[(1-
Antihypeertensive, Hypertension, general
methylethyl)amino]propoxy]-[CAS]
73677-19-7
atenolol + Benzeneacetamide, 4-[2-hydroxy-3-[(1-
methylethyl)amino]propoxy]-, mixt. with
2-chloro-5-(2,3-dihydro-1-hydroxy-3-
3,836,671
oxo-1H-isoindol-1-
yl)benzenesulfonamide [CAS]
methylethyl)amino]propoxy]- + 4-(2′-
nitrophenyl)-2,6-dimethyl-3,5-
dicarbomethoxy-1,4-dihydropyridine
136816-75-6
1H-Imidazole, 4-(2-ethyl-2,3-dihydro-
104054-27-5
Reproductive/gonadal, Sexual dysfunction, 1H-inden-2-yl)-[CAS]
atiprimod 2-Azaspivo[4.5]decane-2-
130065-61-1
5,744,495
Antiarthritic, Arthritis, rheumatoid
propanamine, N,N-diethyl-8,8-dipropyl,
6,232,297
Benzenepropanamine, N-methyl-
Attention deficit Gamma-(2-methylphenoxy)-, (R)-
1H-Pyrrole-1-heptanoic acid, 2-(4-
fluorophenyl)-β,delta-dihydroxy-5-(1-
Hypercholesterol-
methylethyl)-3-phenyl-4-
[(phenylamino)carbonyl]-[CAS]
Oxytocin, 1-(3-mercaptopropanoic
90779-69-4 EP
Labour inhibitor
Labour, preterm
acid)-2-(O-ethyl-D-tyrosine)-4-L-
threonine-8-L-ornithine-[CAS]
1,4-Naphthalenedione, 2-[4-(4-
Infection, chlorophenyl)cyclohexyl]-3-hydroxy-,
atovaquone + 1,4-Naphthalenedione,2-[4-(4-
chlorophenyl)cyclohexyl]-3-hydroxy-,
trans + N-(4-chloro-phenyl)-N-(1-
methylethyl)imidiodicarbonimidic
Isoquinolinium, 2,2′-[1,5-
4,179,557
Surgery adjunct
pentanediylbis[oxy(3-oxo-3,1-
propanediyl)]]bis[1-[(3,4-
dimethoxyphenyl)methyl]-1,2,3,4-
tetrahydro-6,7-dimethoxy-2-methyl-
3-Pyrrolidinecarboxylic acid, 4-(1,3-
benzodioxol-5-yl)-1-[2-(dibutylamino)-2-
oxoethyl]-2-(4-methoxyphenyl)-,
(2R,3R,4S)-[CAS]
Atrial 85637-73-6
2019-68-3
Formulation. modified-
Infection, respiratory release, other
Gold, (1-thio-β-D-glucopyranose
3,708,579
Antiarthritic, other
2,3,4,6-tetraacetato-
S)(triethylphosphine)-[CAS]
Aurothio-
Sulfamic acid, [[2,4,6-tris(1-
5,491,172
methylethyl)phenyl]acetyl]-, 2,6-bis(1-
methylethyl)phenyl ester [CAS]
AWD 12-281 [CAS]
Rhinitis, allergic, general
2-Pyrimidinamine, 4-[2-(1-methyl-5-
3,882,105
Antibacteria, other
Infection, nitro-1H-imidazol-2-yl)ethenyl]-,(E)-
1H-Pyrazolo[1,2-a][1,2,4]benzotriazine-
1440629
1,3(2H)-dione, 5-(dimethylamino)-9-
methyl-2-propyl-[CAS]
2H-1,4-Benzoxazine-8-carboxamide, N-
123040-16-4
1-azabicyclo[2.2.2]oct-3-yl-6-chloro-3,4-
123040-94-8
dihydro-4-methyl-3-oxo-,
123040-96-0
monohydrochioride-[CAS]
6-[(1-Methyl-4-nitro-1H-imidazol-5-
Formulation, oral, other
Transplant rejection, yl)thio]-1H-purine
AZD-4282
Pain, neuronpathic
3,4 Difluorophenylcyclopropylamine
Nonanedioic acid [CAS]
1(2H)-Phthalazinone, 4-[(4-
chlorophenyl)methyl]-2-(hexahydro-1-
methyl-1H-azepin-4-yl)-,
monohydrochioride [CAS]
3,5-Pyridinedicarboxylic acid, 2-amino-
1,4-dihydro-6-methyl-4-(3-nitrophenyl)-,
3-[1-(diphenylmethyl)-3-azetidinyl] 5-(1-
methylethyl)ester, (+/−)-[CAS]
1830-32-6
9-deoxo-9a-aza-9a-methyl-9a-
4,328,334
Infection, respiratory homoerythromycin-A
tract, lower
92395-24-9
aziocillin
carboxylic acid, 3,3-dimethyl-7-oxo-6-
[[[[(2-oxo-1-
imidazolidinyl)carbonyl]amino]phenyl-
acetyl]amino]-, [2S-
[2.alpha.,5Alpha,6β(S*)]]-[CAS]
27589-33-9
Propanoic acid, 2-[[[1-(2-amino-4-
104184-69-2
thiazolyl)-2-[(2-methyl-4-oxo-1-sulfo-3-
azetidinyl)amino]-2-
oxoethylidene]amino]oxy]-2-methyl-,
[2S-[2Alpha,3β(Z)]]-[CAS]
Sodium 5-isopropyl-3,8-dimethyl-1-
6223-35-4
azulene sulfonate
Penicillin, oral
dimethyl-7-oxo-, 1-
[(ethoxycarbonyl)oxy]ethyl ester, [2S-
[2Alpha,5Alpha,6β(S*)]]-[CAS]
β-(Aminomethyl)-4-
Formulation, implant
chlorobenzenepropanoic acid [CAS]
3-Quinolinecarboxylic acid, 1-
Quinolone antibacterial
cyclopropyl-6-fluoro-1,4-dihydro-8-
methoxy-7-[3-(methylamino)-1-
pipendinyl]-4-oxo-[CAS]
Benzoic acid, 5-[[4-[[(2-
4,412,992
GI inflammatory/bowel Colitis, ulcerative
carboxyethyl)amino]carbonyl]phenyl]azo]-
2-hydroxy-, (E)-[CAS]
Carbamic acid, dimethyl-, 5-[2-[(1,1-
dimethylethyl)amino]-1-hydroxyethyl]-
1,3-phenylene ester,
3703-79-5
2016-63-9
bamidipine
Hypertensive, general
dihydro-2,6-dimethyl-4-(3-nitrophenyl)-,
104757-53-1
methyl-1-(phenylmethyl)-3-pyrrolidinyl
71863-56-4
ester, [S-(R*,R*)]-
N-Methyl-3-[2-(2-
Infection, napthyl)acetylamino]benzamide
Basic 1339-92-0
179045-86-4
Bay-41-2272
5-cyclopropyl-2-[1 (2-fluoro-benzyl)-1H-
Sexual dysfunction, pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-
male, general
4ylamine
Bay-41-8543
2-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-
b]pyridin-3-yl]-5-(4-
mopholinyl)pyrimidine-4,6-diamine
N-(4-chloro-3-(trifluoromethyl)phenyl)-
N′-(4-(2-(N-methylcarbamoyl)-4-
pyridyloxy)phenyl)urea
BAY-57-1293
N-[5(aminosulfonyl)-4-methyl-1,3-
Infection, herpes thiazol-2-yl]-N-methyl-2-[4-(2-
pyridinyl)phenyl]acetamide
TSE 424 [CAS]
b-Benzal-
7236-47-7
BBR-3464
Platinum(4+), hexaaminedichlorobis(μ-
172903-00-3
5,744,497
Cancer, lung, (1,6-hexanediamine-N:N′))tri-
stereoisomer, tetranitrate [CAS]
BBR-3576
5,519,029
BBR-3610
6,060,616
BCH-1868
(−)-2-R-dihydroxyphosphinyol-5-(S)-
(guanin-9-yl-methyl)tetrahydrofuran
Pregna-1,4-diene-3,20-dione, 9-chloro-
Formulation, inhalable, Asthma
11β,17,21-trihydroxy-16β-methyl,
134564-82-2
Ethanone, 1-[7-[2-hydroxy-3-[(1-
39543-79-8
methylethyl)amino]propoxy]-2-
benzofuranyl]-[CAS]
1H-1-Benzazepine-1-acetic acid, 3-[[1-
(ethoxycarbonyl)-3-phenylpropyl]amino]
2,3,4,5-tetrahydro-2-oxo-, [S-(R*,R*)]-
86541-78-8
1-Propanamine, N,N-dimethyl-3-[[1-
14286-84-1
9829409 Vasodilator, peripheral
(phenylmethyl)cycloheptyl]oxy]-, (E)-2-
butenedloate (1:1) [CAS]
L-Lysine, mono[[[1-(phenylmethyl)-1H-
indazol-3-yl]oxy]acetate] [CAS]
20187-55-7
Bendro-
78718-25-9
Ethanol, 2-[[1-methyl-2-[3-
(trifluoromethyl)phenyl]ethyl]amino]-,
benzoate (ester) [CAS]
Benfurodil
3447-95-8
methyl 1-(phenylmethyl)-3-piperidinyl
ester, monohydrochloride (R*,R*)-(+/−)-
5003-48-5
2156-27-6
2H-[1]Benzothieno[2,3-e]-1,4-diazepin-
29462-18-8
2-one, 1,3,6,7,8,9-hexahydro-5-
phenyl[CAS]
Methanone, (3,5-dibromo-4-
3,012,042
hydroxyphenyl)(2-ethyl-3-benzofuranyl)
14051-33-3
N-benzyl-2-nitroimidazole-1-acetamide
17243-39-9
Benzoxonium 19379-90-9
Peroxide, dibenzoyl [CAS]
Benzoylpas
13898-58-3
63-12-7
91-33-8
(phenylmethyl)-1H-indazol-3-yl]oxy]-
Benzylhydro-
1824-50-6
3818-50-6
1-Piperidinebutanoic acid, 4-((4-
9829409
chlorophenyl)-2-pyridinylmethoxy)-, (S)-, 190786-43-7
monobenzenesulfonate [CAS]
1-Pyrrolidineethanamine, β-[(2-
Angina, general
methylpropoxy)methyl]-N-phenyl-N-
74764-40-2
(phenylmethyl)-[CAS]
74764-75-3
1H-Cyclopenta[b]benzofuran-5-
4,474,802
Peripheral vascular butanoic acid, 2,3,3a,8b-tetrahydro-2-
88430-50-6
hydroxy-1-(3-hydroxy-4-methyl-1-octen-
6-ynyl)-[CAS]
Bermoprofen
78499-27-1
119257-34-0
2-Pyndineethanamine, N-methyl-,
Maniere′s disease
Betaine-[CAS]
Metabolic and enzyme Homocystinuria
Pregna-1,4-diene-3,20-dione, 9-fluoro-
Formulation, dermal, Psoriasis
11,17,21-trihydroxy-16-methyl-,
(11β,16β)-[CAS]
3734-24-5
2-Propanol, 1-[4-[2-
4,252,984
(cyclopropylmethoxy)ethyl]phenoxy]-3-
[(1-methylethyl)amino]-[CAS]
55-73-2
b-Eucaine
2-Propanol, 1-[[2-(3,4-
42864-78-8
3,857,891
dimethoxyphenyl)ethyl]amino]-3-(3-
59170-23-9
methylphenoxy)-[CAS]
5205-82-3
Benzoic acid, 4-(1-(5,6,7,8-tetrahydro-
Cancer, lymphoma, 3,5,5,8,8-pentamethyl-2-
naphthalenyl)ethenyl)-[CAS]
Propanoic acid, 2-[4-[2-[(4-
chlorobenzoyl)amino]ethyl]phenoxy]-2-
BG-9928
166374-48-7
BIA-2-024
10,11-dihydro-10-hydroxyimino-5H-
199997-15-4
9745416
Epilepsy, general
dibenz/b,f/azepine-5-carboxamide
(S)-(−)-10-acetoxy-10,11-dihydro-5H-
dibenzo/b,f/azepine-5-carboxamide-
BIA-3-202
1-(3,4-dihydroxy-5-nitrophenyl)-2-
274925-86-9
phenyl-ethanone
Bialamicol
493-75-4
5H-Pyrazolo[1,2-a][1,2,4]triazol-4-ium,
Beta-lactam antibic
Infection, beta-
6-[[2-carboxy-6-(1-hydroxyethyl)-4-
lactamase resistant
methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-
en-3-yl]thio]-6,7-dihydro-, hydroxide,
inner salt, [4R-[4Alpha,5β,6β(R*)]]-
Propanamide, N-[4-cyano-3-
(trifluoromethyl)phenyl]-3-[(4-
fluorophenyl)sulfonyl]-2-hydroxy-2-
3-Azabicyclo[3.1.0]hexane, 1-(4-
methylphenyl)-, (+/−)-[CAS]
71195-57-8
bicyclic U.S.
6,294,585
monoter-
penediols
116078-65-0
Betamiverine
6888-11-5
53-1 8-9
1-Butanamine, N-methyl-4-[2-
62232-46-6
Attention deficit (phenylmethyl)phenoxy]-, hydrochloride
90293-01-9
34633-34-6
1H-Imidazole, 1-([1,1-biphenyl]-4-
4,118,487
Infection, fungal, ylphenylmethyl)-[CAS]
60629-08-5
60629-09-6
5-Heptenamide, 7-(3,5-dihydroxy-2-(3-
5,688,819
hydroxy-5-phenyl-1-
pentenyl)cyclopentyl)-N-ethyl (1R-
(1Alpha(Z)2β(1E,3S,3Alpha,5Alpha))
N-[2-hydroxy-3-(1-piperidinyl)propoxy]-
130493-04-8
5,147,874
Symptomatic antidiabetic
3-pyridinecarboximidoyl chloride, (Z)-2-
butanedioate (1:1)
(1,1-Biphenyl)-3-acetic acid, 3′,3″′-(1,6-
187269-40-5
hexanediyl)bis(6-Alpha-D-
mannopyranosyloxy)-, [CAS]
Adenosine, 2-
144348-08-3
((cyclohexylmethylene)hydrazino)-
6,423,744
2-Piperidinecarboxylic acid, 1-
174254-13-8
Radio/chemosensitizer
(oxo(3,4,5-trimethoxyphenyl)acetyl)-,4-
159997-94-1
(3-pyridinyl)-1-(3-(3-
pyridinyl)propyl)butyl ester, (S)-, 2-
hydroxy-1,2,3-propanetricarboxylate
(1:2) [CAS]
1-Butanone, 1-(4-fluorophenyl)-4-
2333922
(3,4,6,7,12,12a-
hexahydropyrazino[1′,2′:1,6]pyrido[3,4-
b]indol-2(1H)-yl)-[CAS]
Bisdequalinium
52951-36-7
Bismuth 12284-76-3
Bismuth 53897-25-9
Butylthiolaurate
Bismuth Ethyl 52951-37-8
Bismuth 138-58-9
lodosubgallate
Bismuth 53778-50-0
Bismuth Sodium
5798-43-6
Triglycollamate
Bismuth 5892-10-4
Bismuth 22650-86-8
Bismuth 1304-85-4
Bismuth 14882-18-9
Bismuth 5175-83-7
Tribro-
mophenate
2-Propanol, 1-[4-[[2-(1-
Antihypertensive, Heart failure
methylethoxy)ethoxy]methyl]phenoxy]-
3-[(1-methylethyl)amino]-[CAS]
bisoprolol + 2-Propanol, 1-[4-[[2-(1-
Formulation, Hypertension, HCTZ
methylethoxy)ethoxy)methyl]phenoxy]-
3-[(1-methylethyl)amino] mixt. with 6-
chloro-3,4-dihydro-2H-1,2,4-
benzothiadiazine-7-sulfonamide 1,1-
Formulation, Hypertension, trichloro-
methylethoxy)ethoxyjmethyl]phenoxy]-
methiazide
chloro-3-(dichloromethyl)-3,4-dihydro-
2H-1,2,4-benzothiadiazine-7-
sulfonamide 1,1-dioxide
14008-48-1
30392-40-6
BL-3875
Bleomycin [CAS]
Formulation, transdermal, Cancer, head and neck
Cycloocta[b]pyridine, 2-(4-ethyl-1-
piperazinyl)-4-(4-fluorophenyl)-
5,6,7,8,9,10-hexahydro-[CAS]
cis-(+/−)-2-(Ethylthio)-5,7-dihydroxy-8-
9742949
(3-hydroxy-1-methyl-4-piperidinyl)-4H-1
BN-82451
4-[2-(aminomethyl)-1,3-thiazol-4-yl]-2,6-
di-tert-butylphenol, dihydrochloride
BNP-7787
Ethanesulfonic acid, 2,2′-dithiobis-,
16208-51-8
induced nausea [CAS]
5-Benzofuranol, 4,6-bis(1,1-
157360-23-1
9408930
dimethylethyl)-2,3-dihydro-2,2-dipentyl-
1605-89-6
2-Propanol, 1-[(1,1-
4,340,541
dimethylethyl)amino]-3-[(2-methyl-1H-
82857-38-3
indol-4-yl)oxy]-, benzoate (ester), (+/−)-
Bornyl 464-41-5
Bornyl 560-88-3
Boronic acid, [(1R)-3-methyl-1-[[(2S)-1-
6,271,199
oxo-3-phenyl-2-[(pyrazinyl-
carbonyl)amino]propyl]amino]butyl]-
Benzenesulfonamide, 4-(1,1-
Hypertension, dimethylethyl)-N-[6-(2-hydroxyethoxy)-
5-(2-methoxyphenoxy)[2,2-bipynmidin]
4-yl]-[CAS]
BP2.94
Phenol, 2-[[[(1R)-2-(1H-imidazol-4-yl)-1-
139191-80-3
Rhinitis, general
methylethyl]imino]phenylmethyl]
BP4.897
N-[4-[4-(2-methoxyphenyl)-1-
piperazinyl]butyl]naphthalene-2-
b-Propiolactone
140661-97-8
Brain Natriuretic 114471-18-0
8-Azabicyclo(3.2.1)octane-2-
9528401
carboxaldehyde, 3-(3,4-dichlorophenyl)-
8-methyl-, O-methyloxime, (1R-
(1Alpha,2β(E),3Alpha,5Alpha))-[CAS]
96187-53-0
6-Quinoxalinamine, 5-bromo-N-(4,5-
dihydro-1H-imidazol-2-yl)-[CAS]
2H-Thieno(3,2-e)-1,2-thiazine-6-
5,378,703
sulfonamide, 4-(ethylamino)-3,4-
dihydro-2-(3-methoxypropyl)-, 1,1-
dioxide, (R)-[CAS]
Uridine, 5-(2-bromoethenyl)-2-deoxy,
Infection, varicella (E)-[CAS]
56518-41-3
Benzeneacetic acid, 2-amino-3-(4-
Formulation, mucosal, Inflammation, ocular
bromobenzoyl)-[CAS]
1146-98-1
Bromodiphen-
4093-35-0
chloranilide
1-Butanone, 4-[4-(4-bromophenyl)-4-
3,438,991
hydroxy-1-piperidinyl]-1-(4-
fluorophenyl)-[CAS]
Bromphen-
Broparoestrol
479-68-5
56741-95-8
4-(2-Bromoacrylamido)-N′″-(2-
guanidinoethyl)-1,1′,1″,1″′-tetramethyl-
N,4′:N′,4″:N″,4″′-quater-[pyrrole-2-
carboxamide] [CAS]
6H-Thieno[3,2-f][1,2,4]triazolo[4,3-
57801-81-7 U.S.
4,094,984
Hypnotic/Sedative
a][1,4]diazepine, 2-bromo-4-(2-
chlorophenyl)-9-methyl-[CAS]
57475-17-9
1083-57-4
Adenosine, N-(1-oxobutyl)-, cyclic 3′,5′-
51113896
(hydrogen phosphate) 2-butanoate
9-Acridinamine, N-butyl-1,2,3,4-
tetrahydro-, monohydrochloride [CAS]
58409-59-9
Pregna-1,4-diene-3,20-dione, 16,17-
[butylidenebis(oxy)]-11,21-dihydroxy-,
(11β,16Alpha)-[CAS]
budesonide + Pregna-1,4-diene-3,20-dione, 16,17-
(11β,1bAlpha) + formamide, N-[2-
hydroxy-5-[1-hydroxy-2-[[2-(4-
methoxyphenol)-1-
methylethyl]amino]ethyl]phenyl]-
(R*,R*)-(�)
Piperidine, 1-(1,1-dimethylethyl)-4,4-
57982-78-2
diphenyl-[CAS]
63661-61-0
36798-79-5
22103-14-6
53684-49-4
p-butoxyacetohydroxamic acid
3,479,396
1-Butanone, 4-(1-pyrrolidinyl)-1-(2,4,6-
trimethoxyphenyl)-[CAS]
55837-25-7
S4340-62-4
Benzoic acid, 3-(aminosulfonyl)-5-
3,806,534
(butylamino)-4-phenoxy-[CAS]
1-Naphthalenecarboxamide, N-butyl-N-
32421-46-8
[2-(diethylamino)ethyl]-[CAS]
Bunamiodyl 1923-76-8
1H-1,4-Diazepine, 1-(4-amino-6,7-
52712-76-2
1398455 Antihypertens
dimethoxy-2-quinazolinyl)hexahydro-4-
80755-51-7
(1-oxobutyl)-[CAS]
Benzonitrile, 2-[3-[(1,1-
34915-68-9
3,940,489
Antihypertensive, dimethylethyl)amino]-2-
hydroxypropoxy]-[CAS]
2-Piperidinecarboxamide, 1-butyl-N-
(2,6-dimethylphenyl)-[CAS]
release >24 hr
6,14-Ethenomorphinan-7-methanol, 17-
3,433,791
(cyclopropylmethyl)-Alpha-(1,1-
dimethylethyl)-4,5-epoxy-18,19-dihydro-
3-hydroxy-6-methoxy-Alpha-methyl-,
[5Alpha,7Alpha(S)]-[CAS]
1-Propanone, 1-(3-chlorophenyl)-2-
4,425,363
[(1,1-dimethylethyl)amino]-, (+/−)-
4663-83-6
(pig), 6-[O-(1,1-dimethylethyl)-D-serine] 68630-75-1
9-(N-ethyl-L-prolinamide)-10-
deglycinamide-[CAS]
8-Azaspiro[4.5]decane-7,9-dione, 8-[4-
[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-
Formulation, optimized
1,4-Butanediol, dimethanesulfonate-
Formulation, parenteral, Cancer, leukaemia, [CAS]
2109-73-1
22131-35-7
1142-70-7
4-Aminobenzoic acid butyl ester [CAS]
Benzeneacetic acid, Alpha-ethyl-, 2-[2-
18109-80-3
(diethylamino)ethoxy]ethylester, 2-
18109-81-4
(1:1) [CAS]
653-03-2
55837-14-4
16790-49-1
Butedronic 51395-42-7
1-Naphthalenemethanamine, N-((4-
Infection, (1,1-dimethylethyl)phenyl)methyl)-N-
Butethamate
14007-64-8
2090-89-3
1506-12-3 butobendine
benzoic acid, 3,4,5-trimethoxy-, 1,2-
4,021,473
ethanediylbis[(methylimino)(2-ethyl-2,1-
ethanediyl)] ester, [S-(R*,R*)]-[CAS]
1H-Imidazole, 1-[4-(4-chlorophenyl)-2-
Infection, Candida, [(2,6-dichlorophenyl)thio]butyl]-, (+/−)-
Morphinan-3,14-diol, 17-
(cyclobutylmethyl)-, [S-(R*,R*)]-2,3-
dihydroxybutanedioate (1:1) (salt)
3772-43-8
35941-65-2
Butropium
29025-14-7
Buzepide
3691-21-2
0208178
Anorectic/Antiobesity
BXT-51072
2H-1,2-Benzoselenazine, 3,4-dihydro-
173026-17-0
4,4-dimethyl-[CAS]
6H-Imidazo[4,5,1-de]acridin-6-one, 5-
[[2-(diethylamino)ethyl]amino]-8-
hydroxy-, 2HCl, 2H2O
Ergoline-8-carboxamide, N-[3-
(dimethylamino)propyl]-N-
85329-89-1
[(ethylamino)carbonyl]-6-(2-propenyl)-,
(8β)-[CAS]
Cacodylic 75-60-5
cadexomer Cadexomer iodine [CAS]
Ulcer, venostasis
Cadmium 19010-79-8
64241-34-5
30924-31-3
1,2,3,-Propanetncarboxylic acid, 2-
hydroxy- mixt. with 3,7-dihydro-1,3,7-
trimethyl-1H-purine-2,6-dione [CAS]
9,10-Secochola-5,7,10(19),22-tetraene-
1,3,24-triol, 24-cyclopropyl-,
(1Alpha,3β,5Z,7E,22E)-[CAS]
calcipotriol + 9,10-Secochola-5,7,10(19),22-tetraene-
(1Alpha,3β,5Z,7E,22E) + Pregna-1,4-
diene-3,20-dione, 9-chloro-11β,17,21-
trihydroxy-16β-methyl, 17,21-
1,3,25-triol, (1Alpha,3β,5Z,7E)-[CAS]
Calcium 3-
5743-29-3
Aurothio-2-
propanol-1-
Calcium 69-46-5
Calcium 33659-28-8
Bromolac-
tobionate
Calcium 471-34-1
Calcium 299-28-5
Calcium 27214-00-2
calcium Calcium D-(+)-4-(2,4-dihydroxy-3,3-
17097-76-6
Attention deficit hopantothenate
dimethylbutyramido)butyrate
(hemihydrate) [CAS]
Calcium 1319-91-1
lodobehenate
Calcium 1301-16-2
lodostearate
Calcium 814-80-2
Calcium 591-64-0
Calciuhi 21085-60-9
Calcium N-
16649-79-9
calcium Polycarbophil, calcium salt-[CAS]
126040-58-2
GI inflammatory/bowel Irritable bowel polycarbophil
Calcium 4075-81-4
Calcium 140-99-8
5-methyl-2-(1-piperazinyl)-
133804-44-1
17021-26-0
Benzeneacetic acid, 4-[[4-
59721-28-7
4,021,472
GI inflammatory/bowel Pancreatitis
[(aminoiminomethyl)amino]benzoyl]oxy]-,
2-(dimethylamino)-2-oxoethyl ester,
monomethanesulfonate [CAS]
Camphotamide
4876-45-3
4-Ethyl-4-hydroxy-1H-pyrano-
[I3′4′:6,7]indolizinol[1,2-b;]quinoline-
3,14(4H,12H)-dione
candesartan 1H-Benzimidazole-7-carboxylic acid, 2-
ethoxy-1-[[2′-(1H-tetrazol-5-yl)[1,1′-
biphenyl]-4-yl]methyl]-, 1-
[[(cyclohexyloxy)carbonyl]oxy]ethyl
ester, (+/−)-[CAS]
123122-55-4
N-[4-(3-(Chloro-4-fluoro-phenylamino)-
Cancer, lung, 7-(3-morpholin-4-yl-propoxy)-quinazolin
6-yl]-acrylamide
cantuzumab Maytansine, N2-deacetyl-N2-(3-
139504-50-0
mercapto-1-oxopropyl)-, conjugated
humanized C242 monoclonal antibody
Cytidine, 5-deoxy-5-fluoro-N-
Anticancer, Cancer, breast
[(pentyloxy)carbonyl]-[CAS]
Capobenic 21434-91-3
1H-imidazole-2-methanol, 5-(3,5-
178979-85-6
dichlorophenyl)thio-4-(1-methylethyl)-1-
(4-pyridinyl)methyl carbamate (ester)
151763-64-3
capsaicin N-[(4-hydroxy-3-methoxyphenyl)methyl]
Formulation, dermal, Pain, post-herpetic
8-methyl-, (E)-[CAS]
L-Proline, 1-(3-mercapto-2-methyl-1-
4,105,776
oxopropyl)-, (S)-[CAS]
captopril + L-Proline, 1-(3-mercapto-2-methyl-1-
110075-07-5
4,217,347
Antihypertensive, renin HCTZ
oxopropyl)-, (S)-, mixt. with 6-chloro-
3,4-dihydro-2H-1,2,4-benzothiadiazine-
7-sulfonamide 1,1-dioxide [CAS]
5579-13-5
carabersat
Benzamide, N-(6-acetyl-3,4-dihydro-3-
184653-84-7
9811890
hydroxy-2,2-dimethyl-2H-1-benzopyran-
4-yl)-4-fluoro, (3R-trans)-[CAS]
2-Propanol, 1-(9H-carbazol-4-yloxy)-3-
Antihypertensive, [(1-methylethyl)amino]-[CAS]
Carbamide 124-43-6
51460-26-5
Methyl-2-benzimidazolecarbamate
Carbonic acid disodium salt, mixt. with
72227-05-5
Alimentary/Metabolic, Acidosis
monosodium salt-[CAS]
carbidopa + S-Alpha Hydrazino-3,4-dihydroxy-Alpha
levodopa-1
methyl benzene propanoic acid
monohydrate + 3-hydroxy-L-tyrosine
486-16-8
541-79-7
151756-26-2
Carbon 56-23-5
Platinum, diammine[1,1-
cyclobutanedicarboxylato(2-)]-, (SP-4-
2)-[CAS]
carboprost Prosta-5,13-dien-1-oic acid, 9,11,15-
3,728,382
trihydroxy-15-methyl-,
(5Z,9.alpha.,11Alpha,13E,15S)-,
compd. with 2-amino-2-
(hydroxymethyl)-1,3-propanediol(1:1)
2,5-Cyclohexadiene-1,4-dione, 2-[2-
[(aminocarbonyl)oxy]-1-methoxyethyl]-
3,6-bis(1-aziridinyl)-5-methyl-[CAS]
960-05-4
34866-47-2
3567-38-2
N-Carbamoyl-L-glutamic acid
Metabolic and enzyme Hyperammonaemia
33605-67-3
35531-88-5
Benzamide, N-(aminoiminomethyl)-4-
159138-80-4
(1-methylethyl)-3-(methylsulfonyl)-
159138-81-5
1(2H)-Pyrimidinecarboxamide, 5-fluoro-
Anticancer, N-hexyl-3,4-dihydro-2,4-dioxo-[CAS]
98323-83-2
Urea, N,N-bis(2-chloroethyl)-N-nitroso-
461-06-3
23465-76-1
18464-39-6 Carphenazine
9H-Carbazole-2-acetic acid, 6-chloro-
53716-49-7 U.S.
3,896,145
Alpha-methyl-, (+/−)-[CAS]
2(1H)-Quinolinone, 5-[3-[(1,1-
3,910,924
Antihypertensive, Glaucoma
hydroxypropoxy]-3,4-dihydro-,
87638-04-8
Antihypertensive, Hypertension, [[2-(2-methoxyphenoxy)ethyl]amino]-
Pneumocandin B0, 1-((4R,5S)-5-((2-
9421677
aminoethyl)amino)-N2-(10,12-dimethyl-
1-oxotetradecyl)-4-hydroxy-L-ornithine)
5-(threo-3-hydroxy-L-ornithine)-,
diacetate (salt) [CAS]
cathepsin K N-(1-benzothien-2-ylcarbonyl)-N-[2-(2-
9613523
fluorophenyl)-4-oxo-1,2,3,4-
tetrahydropyrimidin-5-yl]-L-leucinamide
cathepsin S N-(1-benzothien-2-ylcarbonyl)-N-[2-(2-
6,342,595
Rapamycin 42-(3-hydroxy-2-
(hydroxymethyl)-2-methylpropanoate)
CCR5 WO
9732019
CDC-394
CDC-801
5,605,914
CEE-03-310
1H-3-Benzazepin-7-ol, 5-(2,3-dihydro-7
128022-68-4
benzofuranyl)- 2,3,4,5,-tetrahydro-3-
methyl-8-nitro, (5S)-[CAS]
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-
Cephalosporin, oral
Infection, carboxylic acid, 7-
70356-03-5
[(aminophenylacetyl)amino]-3-chloro-8-
oxo-, [6R-[6Alpha,7β(R*)]]-[CAS]
carboxylic acid, 7-[[amino(4-
hydroxyphenyl)acetyl]amino]-3-methyl-
8-oxo-, [6R-[6Alpha,7β(R*)]]-[CAS]
8105879-42-3
4,775,751
Infection, respiratory carboxylic acid, 7-
tract, upper
[(aminophenylacetyl)amino]-3-methyl-
oxo-, [CAS]
cefalexin 5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-
27726-31-4
carboxylic acid, 7-
[(aminophenylacetyl)amino]-3-methyl-8
oxo-, (2,2-dimethyl-1-
oxopropoxy)methyl ester,
monohydrochloride, [6R-
[6Alpha,7β(R*)]]-[CAS]
7-D-mandeiamido-3[[(1-methyl-1H-
Cephalosporin, Infection, general
tetrazol-5-yl)thio]methyl]-3-cephem-4-
51627-14-6
hydroxyphenyl)acetyl]amino]-8-oxo-3-
[(1H-1,2,3-triazol-4-ylthio)methyl]-, [6R-
56187-47-4
Cefbuper-
cefcapene 7β-[(Z)-2-(2-amino-4-thiazolyl)-2-
Infection, respiratory pivoxil
pentenoylamino]-3-
105889-46-1
carbamoyloxymethyl-3-cephem-4-
carboxylic acid, pivaloyloxymethyl ester
HCl-[CAS]
105239-91-6
5-Thia-1-azabicyclo(4.2.0]oct-2-ene-2-
Infection, carboxylic acid, 7-[[(2-amino-4-
thiazolyl)(hydroxyimino)acetyl]amino]-3-
ethenyl-8-oxo-, [6R-[6Alpha,7β(Z)]]-
cefditoren 5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-
61178991
carboxylic acid, 7-[[(2-amino-4-
thiazolyl)(methoxyimino)acetyl]amino]-
3-[2-(4-methyl-5-thiazolyl)ethenyl]-8-
oxopropoxy)methyl ester, [6R-
[3(Z),6Alpha,7β(Z)]]-[CAS]
Pyrrolidinium, 1-[[7-[[(2-amino-4-
107648-80-6
Cephalosporin, Infection, thiazolyl)(methoxyimino)acetyl]amino]-
respiratory tract, 2-carboxy-8-oxo-5-thia-1-
azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-
methyl-, hydroxide, inner salt, [6R-
[6Alpha,7β(Z)]]-[CAS]
cefetamet 5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-
3-methyl-8-oxo-, (2,2-dimethyl-1-
thiazolyl)[(carboxymethoxy)imino]acetyl
]amino]-3-ethenyl-8-oxo-, [6R-
Cephalosporin, Infection, ocular
3-[[(1-methyl-1H-tetrazol-5-