ICECREAM-TYPE PHARMACEUTICAL FORMULATION AND PROCESS FOR PREPARING THE SAME

Abstract: The present invention relates to a soft icecream-type pharmaceutical formulation and a process for preparing the same. The icecream-type pharmaceutical formulation of present invention is prepared by the steps of mixing egg yolk, milk, and cocoa with stirring until the cocoa is completely dissolved in the mixture; whipping a cream until it is reduced to pulp and mixing it with the said mixture in a volume ratio of 9:1 to 5:5; adding drugs into the said mixture and blending them; and, putting them into an ice cream maker and formulating into a pharmaceutical formula. Since a soft ice cream-type-formulation of the invention has merits over conventional formulas in terms of taking preference and absorbtion efficacy in oral application, it can be used as an improved pharmaceutical formula for children and infants, while substituting for troches.

Description: ICECREAM-TYPE PHARMACEUTICAL FORMULATION AND PROCESS FOR PREPARING THE SAME BACKGROUND OF THE INVENTION field of the invention The present invention relates to a soft icecream-type pharmaceutical formulation and a process for preparing the same . Description of the Prior Art Antipyretics, antibiotics and vitamins have been conventionally formulated in the forms of tablet, capsule, liquid, injection solution and syrup. The conventional dosage forms are, however, proven to be less satisfactory in the sense that they are not convenient for administering to children. Accordingly, particular attention should be paid in choosing the dosage forms, especially, orally administrable pharmaceutical formulations are selected under a careful consideration of taste and mouth feel in oral cavity. Unfortunately, many medicines and active ingredients are bitter in taste or else hold uncomfortable taste, rough or chalky feeling. With the recent development in pharmaceutical technology, to improve taste and/or mouth feel in oral cavity, the pharmaceutical formulations of relatively easy administration for children such as chewable tablet, jelly-like tablet, granules, etc., have been developed. They are commercially available though these pharmaceutical formulations are not ideal in terms of children's affinity. Under the circumstances, there are strong reasons for exploring and developing new type of pharmaceutical formulation for children. SUMMARY OF THE INVENTION The present inventors have made efforts to develop an icecream-type pharmaceutical formulation which can be applied in drugs such as antipyretics, antibiotics and vitamins, and found that it provides excellent drug absorption with improved patient's drug compliance in light of easy oral application and high affinity. The primary object of the present invention is, therefore, to provide an icecream-type pharmaceutical formulation. The other object of the invention is to provide a process for preparing the icecream-type pharmaceutical formulation. Another object of the invention is to provide icecream-type formulations of antipyretic, antibiotic and vitamin. BRIEF DESCRIPTION OF THE DRAWINGS The above and the other objects and features of the present invention will become apparent from the following descriptions given in conjunction with the accompanying drawings, in which: Figure 1 is a high performance liquid chromatography chromatogram of acetaminophen in blood. Figure 2 is a graph showing blood level of tablet- type and icecream-type acetaminophen after oral administration. DETAILED DESCRIPTION OF THE INVENTION Icecream-type pharmaceutical formulation of the present invention is prepared by the steps of: mixing egg yolk and milk with stirring until they are completely mixed; whipping cream until it is reduced to pulp and mixing it with the said mixture in a volume ratio of 9:1 to 5:5, more preferably 8:2 to 6:4, most preferably 7:3; adding drugs into the said mixture in a ratio of 0.1 to 20wt% and blending them; and, finally putting them into an icecream maker and formulating into a pharmaceutical formula by subjecting at the temperature range of 0°C to -10°C. In the preparation of the icecream-type formulation, sugar and/or cocoa may be further added to the mixture of egg yolk and milk according to the patient's preference, and coconut hard fat may substitute for the egg yolk. Further, the milk includes soy bean milk, processed skim milk (containing 7.2% skimmed milk powder) and plain milk. And, the cream includes: commercially available emulsion cream which can be obtained by the centrifuge of animal/vegetable oil; and, carboxymethylcellulose (CMC) solution. Though several pharmaceutical formulations of antipyretics, antibiotics or vitamins are illustrated in the Examples below, they do not specifically limit the drugs contained in the formulation. The antipyretics include acetaminophen, aspirin, ibuprofen, ketoprofen and isopropyl-antipyrin, preferably acetaminophen and/or mixture thereofs, the antibiotics include amoxicillin, ampicillin, erythromycin, lincomycin, and cefalexin, most preferably amoxicillin, and the vitamins include retinol acetate, cholecalciferol, tocopherol acetate, ascorbic acid, thiamme nitrate, riboflamin, pyridoxine hydrochloride, πicotinamide and cyanocobalamin. The present invention is further illustrated in the following examples, which should not be taken to limit the scooe of the invention. Example 1: Preparation of icecream-type formulation containing an antipyretic of acetaminophen Example 1-1 Sugar, cocoa, egg yolk and milk were weighed in the ratios shown in Table 1 below, and mixed with stirring until they were completely dissolved. Then, commercially available emulsion cream was whipped until it was reduced to pulp and mixed with the said mixture. And then, acetaminophen, an antipyretic, was added to the mixture, blended, and put in an icecream maker (Philips, HR2034) and subjected at a temperature of 0 ° C to -10 ° C, to give an icecream-type formula. Table 1. The contents of icecream-type formulation containing acetaminophen Example 1-2 An icecream-type antipyretic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 2 below. Table 2. The contents of icecream-type formulation containing acetaminophen Example 1-3 An icecream-type antipyretic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown m Table 3 below. Table 3. The contents of icecream-type formulation containing acetaminophen Example Preparation of icecream-type formulation containing an antibiotic of amoxicillin Example 2-1 An icecream-type antibiotic formulation was prepared m an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 4 below. Table 4: The contents of icecream-type formulation containing amoxicillin Example 2-2 An icecream-type antibiotic formulation was prepared in an analogous manner as in Example 1-1, except for employing tne ingredients shown in Table 5 below. Table 5: The contents of icecream-type formulation containing amoxicillin Example 2-3 An icecream-type antibiotic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 6 below. Table 6: The contents of icecream-type formulation containing amoxicillin Example Preparation of icecream-type formulation containing vitamins Example 3 - 1 : An icecream-type multi-vitamin formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients of retinol acetate, cholecalciferol, tocopheroi acetate, ascorbic acid, th amine nitrate, πboflavm, pyπdoxine hydrochloπde, nicotinamide and cyanocobalamm as shown in Table 7 below. Table 7 : The contents of icecream-type formulation containing vitamins example 3-2: An icecream-type multi-vitamin formulation was prepared m an analogous manner as m Example 1-1, except for employing the ingredients of retinol acetate, cholecalci erol, tocopheroi acetate, ascorbic acid, nitrate, nooflavm, pyπαoxine hydrochloπde, nicotinamide and cyanocobalamm as snown in Table 8 below. Table 8 : The contents o-i icecream-type formulation containing vitamins Example 4 : Measurement of Blood Level of Drugs To measure the blood level of acetaminophen, male SD rats were cannulized in arteriae femoralis after the ether treatment. When the rats were come out of the ether, comm.ercially available acetaminophen tablet and icecream- type formulation were orally administered with an equal amount of lOOmg/kgBW as acetaminophen per each. Blood was collected in an equal interval and injected to high performance liquid chromatography (HPLC) working under the analysis condition below. The HPLC chromatogram of acetaminophen in blood is shown in Figure 1. Condition for HPLC Analysis: Column: Bonaapak C18 (Waters, U.S.A.) Mobile phase: acetcnitrile : 1% acetate (1:9, v:v' flow rate - lml/min Detector: UV spectrophotometer (λ=254nm) Example 5: Changes in Blood Level of Acetaminophen Changes in blood level of acetaminophen were monitored by the method illustrated in Example 4, after oral administration of 50g icecream-type formulation prepared in Example 2-2 (containing 500mg acetaminophen) and commercially available acetaminophen tablet (containing 500mg acetaminophen) in an amount of lOOmg/kg to experimental rats (s≤e.: Figure 2) . As shown in Figure 2, C^., for the icecream-type formulation containing acetaminophen (o) was shown- at 20min while tablet form(*) was at 30min, and the blood level of drug in the icecream- type formulation was 3 times as high as the tablet-type formulation . Example 6: Changes in Blood Level of Amoxicillin Changes in blood level of amoxicillin were monitored by the method illustrated in Example 4, after oral administration of 50g icecream-type formulation prepared in Example 2-2 (containing 500mg amoxicillin) and commercially available amoxicillin capsule (containing 500mg amoxicillin) in an amount of lOmg/kg to experimental rats. As a result, it was clearly determined that both of the icecream-type formulation and capsule-type formulation of amoxicillin showed similar blood level curve. Example 7 : Changes in Blood Level of Tocopheroi Acetate Changes in blood level of tocopheroi acetate were monitored by the method illustrated in Example 4, after oral administration of 50g icecream-type formulation prepared in Example 3-2 ( containing 500mg tocopheroi acetate) and commercially available tocopheroi acetate tablet (containing 500mg tocopheroi acetate) in an amount of lmg/kg to experimental rats. As a result, ooth of the icecream-type formulation and tablet-type formulation of tocopheroi acetate showed similar blood level curve. Acute Toxicity Acute toxicities of icecream-type formulations of antipyretics, antibiotics, and vitamins prepared m Examples 1, 2 and 3 were investigated by employing 5 sets of male and female rats, which revealed that no mortal rat was detected up to the level of 5g/kg/day which is 500 times of antipyretics, 5000 times of antibiotics and 50000 times of vitamins m terms of their effective amounts. The icecream-type formulation of present invention which comprises antipyretic, antibiotic, or vitamin as an active ingredient is formulated for orally applicable purpose, accordance with the conventional formulating method by containing surfactants, excipients, t ctorials, stabilizers, buffers, suspensions, lsotomc solution, and other additives, organic or inorganic carriers. The icecream-type formulation may be administered to children in an oral dosage in an amount of 2 to 20mg/kg(20kg as a standard weight), while it may be varied depending on the type o drugs, medical treatments, diseases, patient's age and duration of medication. As clearly illustrated and demonstrated as above, the present invention provides an icecream-type pharmaceutical formulation and a process for preparing the same. Icecream-type pharmaceutical formulations prepared by the invention have higher drug compliance to children with easy administration and good absorption and thus may substitute for troches . Although the preferred embodiments of the present invention have been disclosed for illustrative purpose, those who are skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.

Claims: WHAT IS CLAIMED IS: 1. An icecream-type pharmaceutical formulation. 2. The icecream-type formulation of claim 1, wherein the drug is antipyretic, antibiotic or vitamin. 3. The icecream-type formulation of claim 2, wherein the antipyretic is selected from the group consisting of acetaminophen, aspirin, - ibuprofen, ketoprofen and isopropylantipyrin . 4. The icecream-type formulation of claim 2, wherein the antibiotic is selected from the group consisting of amoxicillin, ampicillin, erythromycin, lincomycin and cefalexin. 5. The icecream-type formulation of claim 2, wherein the vitamin is retinol acetate, cholecalciferol, tocopheroi acetate, ascorbic acid, thiamine nitrate, riboflavin, pyridoxine hydrochloride, nicotinamide, cyanocobalamin or mixture thereofs . 6. A process for preparing icecream-type pharmaceutical formulation, which comprises the steps of: mixing egg yolk and milk with stirring until they are completely mixed; whipping cream and mixing it with the mixture in a volume ratio of 9:1 to 5:5; adding drugs into the said mixture in a ratio of 0.1 to 20wt% and blending them; and, putting them into an icecream maker and formulating into a pharmaceutical formula. 7. The process of claim 6, further comprising a step of mixing sugar and/or cocoa with the egg yolk and the milk. 8. The process of claim 6, wherein the egg yolk is suostituted with coconut harα fat. 9. The process of claim 6, wherein the milk is substituted with soy bean milk or processed skim milk. 10. The process of claim 6, wherein the cream is carboxymethylcellulose (CMC) solution or emulsion cream which is obtained by the centrifuge of animal/vegetable oil. 11. The process of "claim 6, wherein the drug is antipyretic, antibiotic or vitamin. 12. An icecream-type formulation containing antipyretic prepared by the process of claim 6, which comprises 3.0 to 18.0wt of sugar, cocoa, egg yolk, and cream per each; 0.2 to 10.0wt% acetaminophen; and, milk. 13. An icecream-type formulation containing antibiotic prepared by the process of claim 6, which comprises 3.0 to 18.0 wt% of sugar, cocoa, egg yolk, and cream per each; 0.2 to 10.0w% amoxicillin; and, milk. 14. An icecream-type formulation containing multi- vitamin prepared by the process of claim 6 which comprises 3.0 to 18.0wt% of sugar, cocoa, egg yolk, and cream per each; 0.002 to 0.1wt% retinol acetate; 0.0004 to 0.02wt% cholecalciferol; 0.02 to 1.0wt% tocopheroi acetate; 0.04 to 2.0wt% ascorbic acid; 0.0008 to 0.04wt% thiamine nitrate; 0.0008 to 0.04wt% riboflavm; 0.0012 to 0.06wt% pyridoxine hydrochloride; 0.008 to 0.4wt% nicotinamide; 0.000004 to 0.0002 cyanocobalamm; and, milk.

Inventors: CHEONG HONG-SEOK, HEO MOON-YOUNG, KIM HYUN-PYO, CHEONG, HONG-SEOK, HEO, MOON-YOUNG, KIM, HYUN-PYO
Applicants: CHEONG HONG SEOK, HEO MOON YOUNG, KIM HYUN PYO, MOGAM BIOTECH RES INST, CHEONG, HONG-SEOK, HEO, MOON-YOUNG, KIM, HYUN-PYO, MOGAM BIOTECHNOLOGY RESEARCH INSTITUTE
Application year: 2000
Main classification: A61K9
IPC codes: A61K9, A61K45, A61K47