John L. Haslam

Tableting of controlled release multiparticulates, the effect of millisphere size and protective overcoating

Controlled release enalapril millispheres of different diameters were prepared and tableted with excipients in a 1:1 ratio on a Carver press. Drug release rate profiles showed that the microporous coating on the millispheres was severely damaged during the compression process. Overcoating of the microporous coating with hydroxypropyl methylcellulose E5 (HPMC E5) protects the microporous coating during compression by absorbing and dissipating the compressional forces. This protection becomes more pronounced as the size of the millispheres is reduced. A novel investigation of individual millisphere strength was conducted to identify the most favorable coating and size combination which would preserve the controlled release properties of the millispheres.

Surface wetting effects in the lipid osmotic pump

Abstract An osmotically driven system for the controlled release of lipoidal drugs is described. The system consists of a solid, low melting core surrounded by a semipermeable membrane that controls the rate of drug release. The core contains the drug, a lipid carrier, and an osmotic agent. In operation, water passes through the semipermeable membrane, interacts with the osmotic agent, and increases the pressure within the system, which forces the lipid carrier and drug through orifices in the coating. For this system to pump the lipid carrier rather than the osmotic agent solution, the semipermeable membrane must be preferentially wetted by the lipid phase rather than the aqueous phase containing the osmotic agent. A technique is described for measuring contact angles as an indication of the surface wetting properties of cellulose acetate films in order to predict which membranes might selectively pump the lipid phase in a coated tablet. The results from the contact angle measurements show good correlation with actual tablet performance.

An in vitro drug release rate method for lipoidal materials

Abstract A multiparticulate preparation of an osmotically mediated, controlled release system for lipoidal materials is described. Spherical beads containing a lipid carrier, an osmotic agent and a lipid soluble model drug were made and a microporous, polymeric coating applied. When placed in an aqueous medium, the coated beads controllably released first the lipid carrier (containing the model drug), then the osmotic agent. A technique is described for measuring the in vitro release rate profile of the lipoidal components of the beads using microporous polypropylene films. Sorption of the lipoidal components by the film occurred following release from the beads in an aqueous medium. Films were removed at specific times for analysis. The lipoidal components were extracted from the film with ethanol and the model drug content determined by spectrophotometry. This technique may be useful for other systems requiring release rate/dissolution testing of lipoidal agents in an aqueous medium.