Drug Discov Ther. 2010;4(6):484-492.
Comparative study on the different techniques for the preparation of sustained-release hydrophobic matrices of a highly water-soluble drug.
Abd El-Halim SM, Amin MM, El-Gazayerly ON, Abd El-Gawad NA
The objective of the present study was to control the release of freely water-soluble salbutamol sulphate (SS) over a prolonged period of time by embedding the drug into slowly eroding waxy matrix materials such as Precirol® ATO5, Compritol® 888 ATO, beeswax, paraffin wax, carnauba wax, and stearyl alcohol. The matrices were prepared by either direct compression or hot fusion techniques. The compatibility of the drug with the various excipients was examined using differential scanning calorimetry (DSC). A factorial design was employed to study the effect of polymer type, polymer concentration (15% and 35%), and filler type (Avicel® PH101 and dibasic calcium phosphate dehydrate (DCP) on the in vitro drug release at 6 h. Results of DSC confirmed drugexcipient compatibility. Increasing the polymer ratio resulted in a significant retardation of drug release. The use of DCP resulted in significant retardation and incomplete drug release while the use of Avicel did not. The hot fusion method was found to be more effective than the direct compression method in retarding SS release. A Precirol formulation, prepared using the hot fusion technique, had the slowest drug release, releasing about 31.3% of SS over 6 h. In contrast, Compritol, prepared using the direct compression technique, had the greatest retardation, providing sustained release of 59.3% within 6 h. A hydrophobic matrix system is thus a useful technique for prolonging the release of freely water-soluble drugs such as salbutamol sulphate.