About 60 of drug was released from DLK 1 within the first hour of dissolution

About 60 of drug was released from dlk 1 within the

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About 60% of drug was released from DLK-1 within the first hour of dissolution period. Kollidon SR exerted a more controlled effect on the release of theophylline, e.g., 26%, 48% and 85% of theophylline was released after 12 hours from formulation TPK-3, TPK-2 and TPK-1 con- taining 75, 50 and 25% of Kollidon SR respectively. Nei- ther a lag phase nor a burst release was observed with theophylline. Carnauba wax imparted stronger retardation over drug release than that of HPMC. Although the drug release rates from Carnauba wax and HPMC matrices were significantly different (P <0.0001, unpaired t-test), diclofenac sodium exhibited slowest release from both classes of matrices while diltiazem HCl showed the fastest rate of release irrespective of polymeric content (Figure 2 and 3). Figure 2: Mean (± s.d.) percent of drug release from plastic matrix tablets containing (a) 300 mg (b) 200 mg and (c) 100 mg Carnauba wax in dissolution study at pH 1.2 and 6.8 (n=3). TP: Theophylline, DS: Diclofenac sodium and DL: Diltiazem HCl. Figure 3: Mean (± s.d.) percent of drug release from plastic matrix tablets containing (a) 300 mg (b) 200 mg and (c) 100 mg HPMC-15 cps in dissolution study at pH 1.2 and 6.8 (n=3). TP: Theophylline, DS: Diclofenac sodium and DL: Diltiazem HCl. This disparity in release rate of different classes of drugs can be attributed to the differences in their physical and chemical properties particularly on the solubility profile (24). Drug particles present in the surface of the matrix is initially released into the surrounding media generating many pores and cracks which facilitates further release of
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J Pharm Pharmaceut Sci () 6(2):282-291, 2003 286 drug. The solubility of diclofenac sodium is 0.187% w/v at pH 6.8 (25). The lower solubility of diclofenac sodium at pH 1.2 limits the initial release of surface drugs as well as the formation of channels within the matrix. Conse- quently, the overall release of diclofenac sodium is decreased. The initial lag period of 2 hours is due to the acidic nature of diclofenac sodium. The drug, being a weak acid (pk a 4.0) is practically insoluble in acidic solution but dissolves readily in intestinal fluid and water (26). Similar result was also reported by Billa et al (27). Diltiazem HCl is an acidic salt of basic drug having a pK a value of 7.7 and the molecule is freely soluble in water. Alderman reported that, the release kinetics of hydrosolu- ble drugs is mainly governed by diffusion from hydrophilic matrices (28). Diltiazem HCl present in the surface of kol- lidon SR matrix tablet rapidly leaves the matrix system because of its basic nature. The burst effect observed with diltiazem HCl from formulations DLK-2 and 3 can be attributed to rapid ionization and higher solubility of dilt- iazem in acidic medium as well as the non-swellable prop- erty of Kollidon SR. Release of theophylline from Kollidon SR matrix, on the other hand, was found to be higher than that of diclofenac sodium. The fact is attribut- able to the higher pk a value (pk a 8.6) and solubility profile of theophylline in both type of dissolution medium with pH value of 1.2 and 6.8. It has been reported that, theo-
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