The discussion of the doctoral thesis by Masters/ Osama Shawky Tawfick – assistant teacher in department of Pharmaceutics and industrial pharmacy – Faculty of Pharmacy

The discussion of the doctoral thesis by Masters/ Osama Shawky Tawfick – assistant teacher in department of Pharmaceutics and industrial pharmacy – Faculty of Pharmacy The discussion of the doctoral thesis by Masters/ Osama Shawky Tawfick – assistant teacher in department of Pharmaceutics and industrial pharmacy – Faculty of Pharmacy – October 6 University was held on Monday 7/1/2013 in the seminar hall in Faculty of Pharmacy – Cairo University. Under the title of: “Hot Melt as a Technique for Enhancement of Drug Performance” Under the supervision of: - Prof. Dr. Alia A. Badawi. Professor of Pharmaceutics - Faculty of Pharmacy - Cairo University. - Prof. Dr. Wedad S. Sakran. Professor of Pharmaceutics - Faculty of Pharmacy - Helwan University. The committee of discussion consisted of: - Prof. Dr. Alia A. Badawi. Professor of Pharmaceutics - Faculty of Pharmacy - Cairo University. - Prof. Dr. Wedad S. Sakran. Professor of Pharmaceutics - Faculty of Pharmacy - Helwan University. - Prof. Dr. Omaima Samour. Professor of Pharmaceutics - Faculty of Pharmacy – Ein Shams University. - Prof. Dr. Nabaweya Abdel Aziz. Professor of Pharmaceutics - Faculty of Pharmacy – October 6 University. English Abstract The work in this thesis aimed to prepare improved formulations of a model drug (griseofulvin) using hot melt extrusion technique. The work also involved construction and validation of a lab-scale single screw extruder to be applicable for the research trials. Thus the work in this thesis is divided into two parts: Part (I): Construction and Validation of a laboratory Scale locally Manufactured Single Screw Extruder. The work in this part aimed to construct and validate a national lab-scale single screw extruder to be suitable and applicable for research trials and formulations of new formulae using hot melt extrusion technique. The barrel length / diameter (L/D) were constructed in ratio of 20/1 (590 mm /30 mm), such ratio was chosen as short L/D extruder which possesses various advantages over long L/D extruder. The Screw root diameter was constructed in increasing circumference The space between screw diameter and width of the barrel is normally 0.2 mm along the length of the screw to ensure efficient compression of polymer. The screw compression ratio was 4.09:1. The die opening of extruder was round with diameter of 2 mm. The body of the extruder (barrel and screw) was constructed using stainless steel (type 440B). Three heaters are fitted around the outer wall circumference of the extruder barrel to control the temperature of operating process. The motor of the extruder was 0.5 horsepower (0.37 kilowatts), a gearbox was used for constant rotation speed at 40 rpm. Validation of the extruder controlled parameters was done, and it was found that the average screw rotations per minute for empty and loaded extruder were 40 rpm at different time intervals. No significant difference was observed in the temperatures detected by external sensors and temperatures expressed on the control unit screen. In process validation at different operating temperatures, and the polymer mass flow rate (M) of Eudragit E100 and the extruder filling ratio (f) were measured as a function of the operation temperature. It was noticed that the flow rate and filling ratio of polymer increased with increasing operating temperature. The residence time distribution (RTD) was determined by the impulsion-response technique using 0.05% Erythrosine red dye in Eudragit E100. Values of experimentally calculated mean residence time (MRT) were less than calculated geometric residence time (GRT) at the same operating temperatures. It was found that the residence time distribution decreased with increasing operating temperature. The ratio of the mean residence time to the geometrical residence time decreased with temperature. This ratio, when less than one, was characteristic of the presence of dead zones in the extruder whose extent decreased when decreasing the temperature. The constructed single screw extruder was found to be suitable for small scale extrusion of pharmaceutical polymeric systems. Part II: Formulation and Characterization of Glibenclamide Self-Microemulsifying Drug Delivery Systems The work in this part aimed to prepare griseofulvin solid dispersions with improved solubility by hot melt extrusion technique using the constructed single screw extruder. Solubility parameter and glass transition were used to select suitable polymers and excipients for this improvement. From data of solubility parameter three polymers out of five were selected for further investigation. Such polymers, PVPK30, HPMC and PEG6000 could be suitable polymeric carriers for griseofulvin hot-melt solid dispersion. DSC thermogram of pure griseofulvin showed a sharp melting peak temperature at 218°C, whereas amorphous PVPK30 and HPMC exhibited a Tg at 164 and 141oC, respectively. Preliminary study was done by melting small quantities of griseofulvin with selected carriers to assess the most suitable selected polymer to prepare griseofulvin solid dispersions by hot melt extrusion technique. Hot-melt blends were containing 25% griseofulvin with different polymers. Starch and lactose were added as distributing agent and aid griseofulvin dissolution from high viscosity hydrophilic polymer. All 16 formulae showed dissolution percentages over 50% after 15 minutes, except formulae prepared using PVPK30 and HPMC F5 and F6, respectively. All formulae containing starch namely; F1, F3, F9, F11, F13 and F15 showed percentage dissolution of griseofulvin higher than formulae containing lactose. From previous dissolution data six formulae were expected to form glass solution or amorphous drug distribution in selected carriers for hot melt extrusion process in the constructed single screw extruder. The drug was uniformly distributed all over the extrusion process. Dissolution data of griseofulvin from different extrudate showed that, the prepared ternary systems of griseofulvin with 2 carriers exhibited higher dissolution than the prepared binary systems. The dissolution rate of the drug from ternary systems containing PEG 6000 seemed to be generally higher than from systems containing HPMC or PVPk30, alone. Melt extrudate containing starch (F15 containing HPMC/PEG6000 1:1, 50% and starch 25%) showed the highest percentage of dissolution after 15 and 90 minutes, which were 69% and 98%, respectively. Melt extrusion of griseofulvin could minimize therapeutic doses and reduction in drug-related side effects.