Drug release from soft gelatin capsules

An in vitro model previously developed, has been modified and used to study the effect of the encapsulation of lipophilic solutions of drugs in soft gelatin capsules on release. The model enables simultaneous measurement of the release and the permeation of a drug from an oily solution, and hence the assessment of in vitro availability. The introduction to the thesis covers four themes: 1) Bioavailability of drugs 2) The release of drugs from lipophilic dosage forms 3) Soft gelatin capsules - properties and uses 4) In vitro assessment of drug availability 4-Hydroxy benzoic acid was chosen as the model compound in the initial studies to determine the effect of reducing the volume of lipophilic solutions added to the apparatus. The solvents used were n-octanol and isopropyl myristate. Reduction of volume resulted in an increased weight fraction released, dependent upon the initial concentration of solute. The ratio of the transfer rate constants obtained could be related to partition coefficients by a factor of the aqueous/oil volume ratio. The encapsulation of the model compound and subsequent analysis in the apparatus resulted in an altered release profile to an unencapsulated solution. During manufacture some of the solute had transferred to the soft gelatin capsule shell. Release depended upon the quantity in the shell and its dissolution. soon as the lipophilic solution came Transfer to the shell occurred as into contact with the shell and continued until it reached equilibrium after the drying stages. A number of solutes - acetomenaphthone, ephedrine, phenobarbitone and thymol were encapsulated in a range of solvents. The release profiles obtained depended upon the amount of drug in the capsule shell. The transfer depended upon the drug, the encapsulated solvent and also upon the size of the capsule; the smaller capsule shell containing comparatively more than larger ones. Transfer was controlled by aqueous solubility and partitioning between the capsule contents and the shell. The greater the aqueous solubility the higher the transfer while the greater the partition coefficient the lower the transfer. Physicochemical studies on the drugs confirmed the transfer to the shell to be dependent upon aqueous solubility and partition coefficient.