Problems in the formulation and manufacture of conventional solid dose form products include the variation of fill weight and drug content, dissolution control of poorly water soluble drugs and dust generated during manufacture giving rise to cross contamination. We have examined the application of a liquid filling technique for the manufacture of hard gelatin capsules as a means of overcoming some of these. Filling materials are based on water-soluble hot melt polymers such as polyethylene glycol or water-dispersible thixotropic systems of pharmaceutical oils with thixotropic additives. A Zanasi LZ64 capsule filling machine was adapted to fill liquids using a liquid filling pump. No dust is generated during filling and 20 pg doses of drug can be accurately filled without extensive processing. The formulations are simple and do not require specialist ingredients such as lubricants, binders, disintegrants and flow aids. The method of manufacture is reduced to a simple mixing and direct filling operation. The system may be applied to promote the dissolution of poorly water soluble drugs using solid solutions or solid dispersions. Slow release formulations are also available using suitable retard excipients.The use of solid solutions and solid dispersions has been widely advocated as a means of overcoming dissolution problems of poorly water soluble drugs, for instance, tolbutamide (Salib et al 1976), griseofulvin, cardiac glycosides and steroids (Chiou & Riegelman 1971) and riboflavine (El-Gindy & El-Khawas 1977). Few conventional dosage forms have exploited these advantages, probably because of the poor processing properties of solid solution systems, which tend to be wax-like materials difficult to handle on high speed tableting and capsule filling machinery (Wells et al 1975). Many solid solution systems require pulverization before they can be filled into capsules (Chiou & Smith 1971).We have evaluated a means of filling liquids into hard gelatin capsules as a way of reducing the problems of conventional pharmaceutical processing methods (Walker et al 1977).Many excipients are claimed to be suitable for use in capsule filling of thixotropic or molten liquids (CuinC et al 1978a(CuinC et al , 1978b
M A T E R I A L S A N D M E T H O D SCapsule filling machine modifications An automatic capsule filling machine (Model Zanasi LZ64, ACM Machinery Ltd.) was adapted to fill liquids instead of powders by replacing the powder hopper and dosator tubes by a liquid filling pump (Precision Shot Dispenser, Model PKM 161, Kent Moore).Synchronization of the filling operation with the positioning of an empty capsule body at the filling station is achieved by a microswitch located at Turntable station G (Fig. 1). The microswitch is activated by the capsule body holding bush as it comes to rest at station G during the intermittent cycle of operation. Actuation of the microswitch opens the valve of the dispenser and a controlled shot of liquid is delivered to the capsule body at the filling station via the filling nozzle. The dispe...
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