Daniela Allhenn1, Alf Lamprecht. 1. Laboratory of Pharmaceutical Engineering, Institute of Pharmacy, University of Bonn, Gerhard-Domagk-Str 3, 53121 Bonn, Germany.
Abstract
PURPOSE: At laboratory scale, the most widely applied methods in therapeutic microencapsulation are based on emulsification using organic solvents. Here, glycofurol was proposed as non-toxic solvent to circumvent these inconveniences using a quasi-emulsion extraction method for the preparation of poly (lactide-co-glycolide) microspheres. METHODS: Matrix polymer and lipophilic drug were dissolved in glycofurol, building the internal phase, and emulsified under stirring into various external phases before microspheres could be obtained and characterized for their pharmacotechnical properties. RESULTS: Microspheres were spherical with particle diameters around 100 to 200 μm and also showed a monomodal particle size distribution. The internal sponge-like structure was related to an incomplete glycofurol extraction (residual content: 16.9% ± 1.6% of total particle mass), which is, however, no toxicological drawback. The encapsulation rate of several model compounds increased with rising partition coefficient (Ibuprofen: 1.9% ± 0.6%, Ritonavir: 11.2% ± 0.4%, Lopinavir: 14.0% ± 2.2%, Sudan III: 28.3% ± 0.4%) due to the decreasing solubility in the external phase. In-vitro release kinetics were varying from a complete release after 4 h for Ritonavir to 3 weeks for Sudan III. CONCLUSION: This new method was confirmed to be suitable for the preparation of microspheres with the use of a non-toxic solvent and to allow for the entrapment of lipophilic actives and their controlled release.
PURPOSE: At laboratory scale, the most widely applied methods in therapeutic microencapsulation are based on emulsification using organic solvents. Here, glycofurol was proposed as non-toxic solvent to circumvent these inconveniences using a quasi-emulsion extraction method for the preparation of poly (lactide-co-glycolide) microspheres. METHODS: Matrix polymer and lipophilic drug were dissolved in glycofurol, building the internal phase, and emulsified under stirring into various external phases before microspheres could be obtained and characterized for their pharmacotechnical properties. RESULTS: Microspheres were spherical with particle diameters around 100 to 200 μm and also showed a monomodal particle size distribution. The internal sponge-like structure was related to an incomplete glycofurol extraction (residual content: 16.9% ± 1.6% of total particle mass), which is, however, no toxicological drawback. The encapsulation rate of several model compounds increased with rising partition coefficient (Ibuprofen: 1.9% ± 0.6%, Ritonavir: 11.2% ± 0.4%, Lopinavir: 14.0% ± 2.2%, Sudan III: 28.3% ± 0.4%) due to the decreasing solubility in the external phase. In-vitro release kinetics were varying from a complete release after 4 h for Ritonavir to 3 weeks for Sudan III. CONCLUSION: This new method was confirmed to be suitable for the preparation of microspheres with the use of a non-toxic solvent and to allow for the entrapment of lipophilic actives and their controlled release.
Authors: Nehal A Kasim; Marc Whitehouse; Chandrasekharan Ramachandran; Marival Bermejo; Hans Lennernäs; Ajaz S Hussain; Hans E Junginger; Salomon A Stavchansky; Kamal K Midha; Vinod P Shah; Gordon L Amidon Journal: Mol Pharm Date: 2004-01-12 Impact factor: 4.939