Tripoli University

About Authors:
Abdulrhman A. Akasha
Department of Pharmaceutics, Faculty of Pharmacy,
Tripoli University, Libya-13645
akashaabdu@yahoo.co.uk

Abstract
Bioerodible microspheres may provide a vehicle for achieving good aerosolisation characteristics, whilst offering a slow release depot from the pulmonary deposited fraction.  Polysebasic anhydride (PSA) was synthesised by a melt-polycondensation process using nitrogen gas under high vacuum. The products were characterised by ¹H-NMR (2 & 20 KDa) and DSC (melting point: 68 & 83 ^°C), and with a yield (81 & 89 %) of prepolymer and polymer respectively. The polyanhydride was converted into microspheres using an oil in oil emulsification procedure.  The polymer was dissolved in dichloromethane and using 1 to 5% Span 85 or oleic acid as stabilizer, dispersed into silicone oil. The dichloromethane was removed by evaporation, the microspheres recovered and washed with petroleum ether. Laser diffraction analysis of the microspheres indicated a mean microspheres size <5 mm.  The presence of rough non-porous spheres was demonstrated by SEM.  Initial in vitro experiments were undertaken to examine the degradation rate in 0.1 M phosphate buffer at 37 ^°C, pH 7.4.  The process was followed for 24 hr, by which time 73% of the microsphere mass had eroded. However release of salbutamol base occurred more rapidly with 95% lost within 6-10 hr. The fact that 74% was released in the first 10 min suggest a high fraction of surface adsorbed drug. Microcarrier systems for slow release may provide a vehicle for achieving good aerosolisation characteristics, whilst offering a slow release depot from the pulmonary deposited fraction. The produced rough and non-porous microspheres containing salbutamol base were subjected for Deposition process using Andersen Mark II Cascade Impactor. The Deposition was assessed from both a Spinhaler and Rotahaler after 5s activation at a flow rate of 28.3L/min.  This resulted in an average of 33.5% (Rotahaler and 17.5% (Spinhaler) of the dose found between stages 2 and the filter corresponding to microspheres in the size range 4.7 to 0.4 mm.