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.