Hot melt extrusion (HME) processing for the development of lipid oral solid dosage forms

This research study explores the use of lipids in hot melt extrusion (HME) for the preparation of sustained release solid lipid matrices. The use of lipids instead of polymers is a novel approach with distinct advantageous. Sustained release solid lipid matrices of diclofenac sodium (Df-Na)/Compritol® 888 ATO (888 ATO) prepared using different approaches such as ‘cold’, ‘hot’ and pre-mix’ by applying changes in processing temperature, drug/lipid ratio and composition of the formulation processed by HME and subsequent compression into tablets were investigated. The characterization using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) exhibited Df-Na either in the crystalline or amorphous state depending on the processing methodology. EDX was employed to validate the homogeneous distribution of drug on the surface of the compressed tablets. Solid lipid matrices exhibited sustained release of pre-mix formulations for 12 hr; mainly via controlled diffusion. Studies were conducted to investigate the impact of processing conditions, addition of excipients, drug loading and drug release rate. The co-extrusion was performed by addition of Fujicalin (DCPA) to the binary mixture. The dissolution rates were found to depend on the actual Df-Na loading and the nature of added excipients, while the effect of the processing temperature was negligible. The dissolution mechanism of all extruded formulations obeyed the Peppas–Korsemeyer law, based on the estimated mechanism of all extruded coefficients and the dissolution constant rates, which reflect drug diffusion from lipid matrices. A supplementary study was performed to investigate the effect of food on in vitro drug release for a pediatric application as an extemporaneous preparation. Uniform size (1mm) pellets of Df-Na/888 ATO were investigated in the presence of different food grades such as yogurt, applesauce, mashed potato and hypromellose 2910 suspension by using a dissolution media at three different pH values. Drug release at pH 1.1 and pH 1.6 showed negligible effects in the presence of food, whilst the drug release at pH 5.5 showed a significant effect. The similarity factor f2 revealed similarity in the release profiles of all foods except hypromellose suspension. Furthermore, mapping techniques (EDX and confocal Raman spectroscopy) were employed, albeit with distinct limitations, to characterize the drug content uniformity and distribution of hot-melt extruded paracetamol (PMOL) tablets. PMOL tablets were obtained using HME extrudates by applying ‘hot’ and ‘pre-mix’ approaches to PMOL/888 ATO at different processing temperatures and different formulation compositions. The results showed better homogeneity and uniformity of PMOL in pre-mix formulation compared to the hot-melt extruded formulation.

Level dc:type.qualificationlevel

mphil

Grantor dc:publisher.institution

University of Greenwich

Year dc:date.issued

2013

Author dc:creator

• Vithani, Kapilkumar

Advisors dc:contributor.advisor

• Douroumis, Dionysios
• Boateng, Joshua

• RS Pharmacy and materia medica

Language dc:language

en