The factors involved in mechanisms of availability of different drugs from suppositories with lipophilic excipients were studied by using an in vitro model of the rectal compartment with a porous membrane simulating the rectal barrier. The solubility in water of drugs was found to be the fundamental factor influencing the release rate from suppositories. In fact, following the melting of the suppository at body temperature the drug particles can migrate to the interface with the small volume of rectal secretion where they dissolve. Drug molecules can so diffuse until they come into contact with the rectal barrier through which the drug is absorbed. Drug concentration in the intrarectal aqueous phase produces the gradient against the large volume of the plasma phase. This gradient regulates the diffusion rate through the barrier. A drug with a low water solubility saturates the intrarectal phase at low concentration hindering the subsequent dissolution of the drug particles remaining in the melted excipient. This fact maintains the viscosity of the melted suppository at a ligh level, which slows the migration of the particles. On the other hand, a drug with high water solubility quickly leaves the excipient, producing a high concentration in the intrarectal phase which supports a high diffusion rate across the barrier. The results obtained indicate that drugs with low solubility in water result in low availability, while drugs with good solubility can give an intense and rapid drug supply for a rapid and intense therapeutic response with the dose administered almost completely utilised.
Effect of drug solubility on the in vitro availability rate from suppositories with lipophilic excipients
REALDON, NICOLA;
2000-01-01
Abstract
The factors involved in mechanisms of availability of different drugs from suppositories with lipophilic excipients were studied by using an in vitro model of the rectal compartment with a porous membrane simulating the rectal barrier. The solubility in water of drugs was found to be the fundamental factor influencing the release rate from suppositories. In fact, following the melting of the suppository at body temperature the drug particles can migrate to the interface with the small volume of rectal secretion where they dissolve. Drug molecules can so diffuse until they come into contact with the rectal barrier through which the drug is absorbed. Drug concentration in the intrarectal aqueous phase produces the gradient against the large volume of the plasma phase. This gradient regulates the diffusion rate through the barrier. A drug with a low water solubility saturates the intrarectal phase at low concentration hindering the subsequent dissolution of the drug particles remaining in the melted excipient. This fact maintains the viscosity of the melted suppository at a ligh level, which slows the migration of the particles. On the other hand, a drug with high water solubility quickly leaves the excipient, producing a high concentration in the intrarectal phase which supports a high diffusion rate across the barrier. The results obtained indicate that drugs with low solubility in water result in low availability, while drugs with good solubility can give an intense and rapid drug supply for a rapid and intense therapeutic response with the dose administered almost completely utilised.
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