Ayman Allahham, Peter Stewart and Shyamal Das


Department of Pharmaceutics - College of Pharmacy, Qassim University, P. O. Box 6151 - Postal code 51442 Buraidah, Saudi Arabia
Drug Delivery, Disposition a Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia

Abstract:

Objective: The objective was to use the agglomerate strength distributions to understand the influence of poorly water-soluble agglomerate modifiers on the dissolution of indomethacin from interactive mixtures containing different agglomerate modifiers.

Materials and methods: The dissolution of indomethacin in water from indomethacin alone and from 20% indomethacin and lactose-povidone mixtures containing 1% and 10% of poorly water soluble agglomerate modifiers such as calcium phosphate (CP), calcium sulphate (CS) and talc was measured using an automated DT-6 Erweka dissolution apparatus (Erweka, Germany) following the USP paddle method. Dissolution data were modelled using Sigma Plot software. The agglomerate strength distributions of indomethacin and indomethacin-CP/CS/Talc mixtures (20:10 or 20:1) were determined by Monte Carlo simulation of their particle size distributions, work of cohesion distributions and packing fraction distributions determined by a laser diffraction (Malvern Instruments, Malvern, UK), an inverse gas chromatography (Surface Measurement Systems, London, UK) and a tapped density apparatus (AUTOTAP Quantachrome instruments, USA), respectively.

Results and discussion: The indomethacin dissolved faster from the mixtures containing 10% CP, CS and talc than corresponding mixtures containing 1% or 0% CP, CS and talc. Both the estimated concentrations and the dissolution rate constants for dispersed particles of the mixtures containing 10% CP, CS or talc were significantly higher than the corresponding values for the mixture containing 1% or 0% CP, CS and talc (p<0.05). The agglomerate strengths of 20:10 indomethacin-CP, CS or talc mixtures were smaller than 20:1 indomethacin-CP, CS or talc mixtures which were smaller than indomethacin alone.

Conclusion: The study concluded that the use of poorly water-soluble agglomerate modifier produces agglomerates of lower strength of poorly-water soluble drug resulting in faster dissolution.