Excipient characterization and particle engineering to develop directly compressed orally disintegrating tablets

ODTs have emerged as a novel oral dosage form with a potential to deliver a wide range of drug candidates to paediatric and geriatric patients. Compression of excipients offers a costeffective and translatable methodology for the manufacture of ODTs. Though, technical challenges prevail such as difficulty to achieve suitable tablet mechanical strength while ensuring rapid disintegration in the mouth, poor compressibility of preferred ODT diluent Dmannitol, and limited use for modified drug-release. The work investigates excipients’ functionality in ODTs and proposes new methodologies for enhancing material characteristics via process and particle engineering. It also aims to expand ODT applications for modified drug-release. Preformulation and formulation studies employed a plethora of techniques/tests including AFM, SEM, DSC, XRD, TGA, HSM, FTIR, hardness, disintegration time, friability, stress/strain and Heckel analysis. Tableting of D-mannitol and cellulosic excipients utilised various compression forces, material concentrations and grades. Engineered D-mannitol particles were made by spray drying mannitol with pore former NH4HCO3. Coated microparticles of model API omeprazole were prepared using water-based film forming polymers. The results of nanoscopic investigations elucidated the compression profiles of ODT excipients. Strong densification of MCC (Py is 625 MPa) occurs due to conglomeration of physicomechanical factors whereas D-mannitol fragments under pressure leading to poor compacts. Addition of cellulosic excipients (L-HPC and HPMC) and granular mannitol to powder mannitol was required to mechanically strengthen the dosage form (hardness >60 N, friability <1%) and to maintain rapid disintegration (<30 sec). Similarly, functionality was integrated into D-mannitol by fabrication of porous, yet, resilient particles which resulted in upto 150% increase in the hardness of compacts. The formulated particles provided resistance to fracture under pressure due to inherent elasticity while promoted tablet disintegration (50-77% reduction in disintegration time) due to porous nature. Additionally, coated microparticles provided an ODT-appropriate modified-release coating strategy by preventing drug (omeprazole) release.

Comparison of weight loss outcomes between obese patients with and without Type 2 diabetes attending a weight management focused structured educational group

Aims: Specialist lifestyle management (SLiM) is a medically supported dietetically led structured group education and self-management programme focusing on weight management. Obese patients with Type 2 diabetes are perceived to find it more difficult to lose weight compared with those without diabetes. We aimed to compare the weight loss achieved by obese patients with or without Type 2 diabetes completing the SLiM programme. Methods: A prospective analysis of patients attending SLiM between 2009 and 2013 was conducted. Results: There were 454 obese patients (mean age 49.1 ± 11.6years, women 72.5%, body mass index 49.8 ± 9.3kg/m2, weight137.3 ± 28kg). 152/454 patients (33%) had Type 2 diabetes of which 31 (20.4%) were insulin treated. Patients with Type 2diabetes were older (52.4 ± 11.3 vs 47.5 ± 11.4 years, p < 0.001). SLiM resulted in significant weight loss in patients with (136.5 ± 27 vs 130.2 ± 25.3, p < 0.001) or without (137.6 ± 29 vs 132.6 ± 28.4, p < 0.001) Type 2 diabetes. Weight loss was comparable between patients with and without Type 2 diabetes (6.1 ± 7.9 vs5.1 ± 7kg, p = 0.2). The proportion of patients achieving ≥ 10%weight loss was similar between patients with and without Type 2diabetes (10.5% vs 9.9%, p = 0.4). Insulin-treated patients lost similar weight to those not treated with insulin (6.3 ± 9.4 vs 6.1 ± 7.6kg, p = 0.9). After adjustment for age, sex, referral weight and medications, Type 2 diabetes did not predict weight change during the SLiM programme (b = 0.3, p = 0.5). Conclusions: Attending the SLiM groups produces a significant weight loss in patients with Type 2 diabetes which is comparable to those without Type 2 diabetes. Insulin-treated patients lost similar weight to those not on insulin. Weight gain with Type 2 diabetes and insulin treatment is not ‘unavoidable’ if patients receive the appropriate support and education.

Base-free, one-pot chemocatalytic conversion of glycerol to methyl lactate using supported gold catalysts

We report an efficient one-pot conversion of glycerol (GLY) to methyl lactate (MLACT) in methanol in good yields (73 % at 95 % GLY conversion) by using Au nanoparticles on commercially available ultra-stable zeolite-Y (USY) as the catalyst (160 °C, air, 47 bar pressure, 0.25 M GLY, GLY-to-Au mol ratio of 1407, 10 h). The best results were obtained with zeolite USY-600, a catalyst that has both Lewis and Brønsted sites. This methodology provides a direct chemo-catalytic route for the synthesis of MLACT from GLY. MLACT is stable under the reaction conditions, and the Au/USY catalyst was recycled without a decrease in the activity and selectivity. From glycerol to green building blocks and solvents! An efficient, base-free conversion of glycerol to methyl lactate in methanol is reported, achieving good yields (73 % at 95 % glycerol conversion) using Au/ultra-stable zeolite-Y (USY) as the catalyst and environmentally benign oxygen as the oxidant by combining two separate reaction steps efficiently in a one pot procedure. The Au/USY catalyst can be recycled without a decrease in the activity and selectivity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.