Patent GB-967610-A (GB)
Title: Sustained release medicament formulations
IPC: A61K31/485
Filed: 1962-10-10
Abstract: A sustained release medicament formulation, in tablet, capsule or pellet form, comprises from 0.5 to 30% of a non-vitamin medicament or a mixture of such medicaments, from 5 to 85% of a carboxylic acid ester having a melting point of 65 DEG  C. or above or a mixture of such esters, and from 1 to 10% of a polyoxyethylene glycol monoester or diester, which esters have the formulae <FORM:0967610/A5-A6/1> and <FORM:0967610/A5-A6/2> respectively in which n is 43 to 137 and R is the hydrocarbyl residue of a C12 and C18 fatty acid, or a mixture thereof; the percentages being based on the total weight of the formulation.  Starch (1 to 20%), lubricant (0.5 to 3%) and filler (1 to 50%) may optionally be present.  The formulations are manufactured by intimately admixing the medicament, polyoxyethylene glycol ester and carboxylic acid ester components and, if desired, any of the above mentioned optional ingredients, and forming the mixture into tablets, capsules or pellets.  In a preferred embodiment, the polyoxyethylene glycol ester and carboxylic acid ester components are melted together at 85 DEG  C. to 120 DEG  C. and the medicament and optional excipients are suspended in the melt which is then chilled by, for example, pan-chilling, drum-chilling or spray-chilling, and the solidified mass is comminuted into pellets which can be converted into tablets or capsules, if desired.  The tablets and pellets provide a sustained release of the medicament by erosion, which gives rise to an initial release of large quantities of medicament and a sustained release of smaller quantities of medicament over relatively long periods of time (e.g. about 4 to 12 hours) so as to maintain the desired blood level.  The tablets and pellets may be sugar or enteric coated if desired, although the taste of the tablets and pellets is not objectionable even when somewhat bitter medicaments are employed. Specified medicaments for use in the invention are dextromethorphan hydrobromide, clidinium bromide, acetylsalicylic acid, phenacetin, phenylephrine and its hydrochloride, phenindamine, amphetamine sulphate, ephedrine hydrochloride, chlordiazepine, chlordiazepoxide hydrochloride and mixtures thereof, and 1-[(41-chlorophenyl) - ethyl] - 2 - methyl - 6,7 - dimethoxy - 1,2,3,4 - tetrahydroisoquinoline. In one of the examples, tablets are illustrated containing, in admixture, acetyl salicylic acid, acetophenetidine, phenylephrine and phenindamine.  The carboxylic acid esters melting above 65 DEG  C. include saturated waxes, e.g. carnauba wax and beeswax; saturated fats, e.g. mixed glyceryl esters of fatty acids such as stearic acid and palmitic acid; glyceryl tristearate and glyceryl tripalmitate; saturated diglycerides of fatty acids, e.g. castorwax; and mixtures of saturated monoglycerides, diglycerides and triglycerides of fatty acids such as stearic acid.  The polyoxyethylene glycol esters may be esters of stearic acid, oleic acid and lauric acid, those specified being polyoxyethylene glycol (6000) distearate, polyoxyethylene glycol (4000) distearate, polyoxyethylene glycol (6000) dioleate, polyoxyethylene glycol (6000) dilaurate, polyoxyethylene glycol (4000) dilaurate and the corresponding monoesters.