Formation of Sustained Release Wax Matrices Within Hard Gelatin Capsules in a Fluidized Bed

Sustained release wax matrices were formed within hard gelatin capsules during fluidization in a hot air stream. The capsules were filled with drug (propranolol HC1 or dieophylline) - wax (Precirol ATO-5 or Gelucire 50/13) powder blends and suspended in a fluidized bed to induce fusion of the wax. Upon cooling, wax matrices with embedded drug were formed in the ends of die capsules. The use of blends of waxes with different HLB values allowed good control over the drug release pattern. The drug release from the matrices was independent of the pH of the dissolution medium. Differential scanning calorimetry was used to study the physical state of the drugs in the matrices. Propranolol HC1 was insoluble and completely dispersed in the wax matrix while theophylline was partially dissolved in the wax.     

Leaching of water-soluble plasticizers from polymeric films prepared from aqueous colloidal polymer dispersions

The leaching of water-soluble plasticizers from polymeric films prepared by casting and drying of plasticized colloidal polymer dispersions was investigated with respect to the type and concentration of plasticizer (triethyl citrate or triacetin), film thickness, type of colloidal polymer dispersions (acrylic: Eudragit RS30D, RL30D, or L30D; cellulosic: Aquacoat), Eudragit RS30D/RL30D ratio, and method of film preparation (solvent- or pseudolatex-casting). The leaching increased with increasing level of plasticizer as indicated by an increase in the release rate constant while the release rate constant was independent of the film thickness. The leaching was more rapid from Aquacoat films than from Eudragit RS30D films at all plasticizer concentrations. Increasing the amount of the more hydrophilic polymer dispersion, Eudragit RL30D, in mixed Eudragit RS/RL films increased the rate of leaching. The incorporation of propranolol HCl into the polymeric films significantly increased the leaching rate constant when compared to drug-free films. The leaching from pseudolatex-cast films was faster when compared to the leaching from solvent-cast films due to the denser structure of the solvent-cast films.     

The Effect of Curing on Drug Release and Morphological Properties of Ethylcellulose Pseudolatex-Coated Beads

Drug-containing nonpareil beads were coated in a fluidized bed with a commercial ethylcellulose pseudolatex, Aquacoat. The drug release was investigated as a function of curing conditions (curing time and temperature) for a hydrophilic and lipophilic drug (chlorpheniramine maleate and ibuprofen) at different levels of plasticizer (triethyl citrate). Curing of coated beads at elevated temperatures immediately after the coating process significantly changed the drug release pattern. Both a retardation and an enhancement in drug release were seen, with the extent being dependent on the type of drug and curing conditions. With chlorpheniramine maleate, a drug with low affinity for the ethylcellulose coating, a curing step was necessary at intermediate plasticizer levels to obtain good film formation and a limiting drug release pattern, while the use of higher plasticizer levels eliminated the need for a curing step. With ibuprofen, a lipophilic drug with high solubility in the ethylcellulose coating, drug crystals were apparent on the bead surface after curing. Curing of ibuprofen beads as a function of time initially decreased but then substantially increased the drug release as a result of drug diffusion across the ethylcellulose membrane with subsequent crystallization on the bead surface. An intermediate seal coat reduced the diffusion of the drug into the ethylcellulose coating.