Abstract
The treatment of type II DM involves the use of combination of drugs, especially at the chronic stage. However, the pill burden of this combination therapy combined with swallowing difficulties, occurring at a later stage of DM, has been the major challenge for successful treatment outcomes. This study was aimed at formulating and optimizing a monolithic fixed-dose combination (FDC) of metformin (MET) and glibenclamide (GLB) orodispersible tablets (ODTs) to overcome both the pill burden and swallowing problems. The FDC ODTs were prepared by the melt granulation technique using polyethylene glycol (PEG) 6000 as a binding agent and crospovidone as a superdisintegrant. In the preliminary study, the effects of sodium lauryl sulphate (SLS), PEG 6000, crospovidone, and compression force on friability, disintegration time, and drug release of tablets were investigated. The FT-IR studies showed that there were no incompatibilities between MET and GLB as well as within excipients. The preliminary studies revealed that PEG 6000 and compression force significantly affect both the friability and the disintegration time, while SLS and crospovidone only affect the disintegration time. Therefore, the effects of PEG 6000, crospovidone, and compression force were further studied and optimized using the central composite design. Accordingly, the most desirable optimal values were obtained at 3.82% of PEG 6000, 9.83% of crospovidone, and 10.6 kN compression force having a friability of 0.302% and a disintegration time of 18.7 seconds. From these results, it can be concluded that a monolithic FDC of MET and GLB ODTs having adequate mechanical strength and faster disintegration time was successfully formulated.
Highlights
Diabetes mellitus (DM) is one of the most prevalent noninfectious diseases characterized by a collection of metabolic disorders which causes hyperglycemia
Drug-Drug and Drug-Excipient Compatibility. e FTIR spectra of the physical mixture of MET HCl, GLB, polyethylene glycol (PEG) 6000, and sodium lauryl sulphate (SLS) are shown in Figure 2. e characteristic peaks of MET HCl are at 3369.70 cm− 1 and 3291.58 cm− 1 (N-H stretching), 2890.38 cm− 1 and 2837.34 cm− 1 (C-H stretching), 1376.23 cm− 1 (N-H bending), and 1018.43 cm− 1 (C-N stretching)
A previous study found that concentration of the binder and superdisintegrant from the formulation variables and compression force from the processing variables are the most important factors that affect the different parameters of orodispersible tablets [15]
Summary
Diabetes mellitus (DM) is one of the most prevalent noninfectious diseases characterized by a collection of metabolic disorders which causes hyperglycemia It is associated with abnormalities in protein, carbohydrate, and fat metabolism which result in severe complications such as microvascular, macrovascular, and neuropathic problems [1]. 3.8 million deaths occurred due to DM [2] From all these deaths, 90–95% were due to type II DM [3]. The use of two or more separate tablets for the management of DM has exposed patients to pill burden which often leads to poor treatment adherence. To improve the treatment adherence of DM patients, a strategy aiming at reducing pill burden and overcoming swallowing difficulty is required. One potential strategy is formulation of fixed-dose combination (FDC) orodispersible tablets (ODTs) to solve both pill burden and swallowing problem. Fixed-dose combinations (FDCs) are a combination of two or more APIs in a single dosage form, which is manufactured in fixed doses, and ODTs are tablets that disintegrate and dissolve rapidly in the saliva, with a few seconds or minutes without the need of water or chewing [7, 8]. us, the aim of this study was to develop the monolithic FDC of metformin hydrochloride and glibenclamide ODTs
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