OBJECTIVE: The objective of this study was to prepare a novel gastric mucoadhesive sustained-release acyclovir (AV)-resinate microsphere. METHODS: First, AV absorption ratio was quantified in a rat gastrointestinal (GI) tract model. AV-resinate was prepared by bath method and used as cores to prepare microspheres by an emulsion solvent diffusion technique with carbopol 934 as coating material. GI transit test of the prepared microspheres was carried out in rats and beagle dogs, followed by the in vivo bioavailability evaluation of the microspheres in beagle dogs. RESULTS: The AV absorption ratio in different segments of rat's GI track for 3 hours was as following: stomach 9.46 +/- 0.62%, duodenum 20.22 +/- 1.50%, jejunum 15.7 +/- 1.33%, ileum 9.15 +/- 1.01%, and colon 4.59 +/- 0.48%. These results showed that AV was mainly absorbed in the stomach and upper intestine. The average diameter of the microspheres was 115.3 microm. The microspheres had a drug content of 33.3 +/- 0.7% (w/w) and a sustained-release profile for 12 hours in vitro. The mucoadhesive test in rats and beagle dogs showed that most of the microspheres were retained in the stomach 6 hours after oral administration. The in vivo pharmacokinetics test revealed that the microsphere and reference (AV tablets) preparations have no significant difference for C(max). The t(max) has increased from 2.33 hours (reference) to 5 hours (test). Meanwhile, the relative bioavailability of AV microspheres was 145%. CONCLUSION: A novel AV-resinate microsphere was prepared. The microspheres were proved to be gastric mucoadhesive and sustained-release with higher bioavailability.
OBJECTIVE: The objective of this study was to prepare a novel gastric mucoadhesive sustained-release acyclovir (AV)-resinate microsphere. METHODS: First, AV absorption ratio was quantified in a rat gastrointestinal (GI) tract model. AV-resinate was prepared by bath method and used as cores to prepare microspheres by an emulsion solvent diffusion technique with carbopol 934 as coating material. GI transit test of the prepared microspheres was carried out in rats and beagle dogs, followed by the in vivo bioavailability evaluation of the microspheres in beagle dogs. RESULTS: The AV absorption ratio in different segments of rat's GI track for 3 hours was as following: stomach 9.46 +/- 0.62%, duodenum 20.22 +/- 1.50%, jejunum 15.7 +/- 1.33%, ileum 9.15 +/- 1.01%, and colon 4.59 +/- 0.48%. These results showed that AV was mainly absorbed in the stomach and upper intestine. The average diameter of the microspheres was 115.3 microm. The microspheres had a drug content of 33.3 +/- 0.7% (w/w) and a sustained-release profile for 12 hours in vitro. The mucoadhesive test in rats and beagle dogs showed that most of the microspheres were retained in the stomach 6 hours after oral administration. The in vivo pharmacokinetics test revealed that the microsphere and reference (AV tablets) preparations have no significant difference for C(max). The t(max) has increased from 2.33 hours (reference) to 5 hours (test). Meanwhile, the relative bioavailability of AV microspheres was 145%. CONCLUSION: A novel AV-resinate microsphere was prepared. The microspheres were proved to be gastric mucoadhesive and sustained-release with higher bioavailability.