Formulation and physicotechnical evaluation of a fixed dose combination of amlodipine, metformin and glibenclamide in the management of hypertension-diabetes mellitus comorbidity

The concept of fixed dose combination (FDC) dates as far back as the early 17th century and still finds relevance till today. Almost every disease condition has at least one approved FDC commercially available for its treatment. The prevalence of hypertension-diabetes mellitus (HTN-DM) comorbidity is high globally. However, there are no available FDC formulation approved to be used in managing patients with this comorbidity. This study was designed to fill this gap by formulating an FDC of Amlodipine (antihypertensive), Metformin (antidiabetic) and Glibenclamide (antidiabetic), which are already being used clinically as monotherapies in management of HTN-DM comorbid patients. The APIs were granulated using wet granulation method with the aid of the excipients, after which the granules properties were examined and subsequently compressed into tablets. The physicotechnical properties and in-vitro release profile were evaluated on the tablets. The results of granule properties such as angle of repose (22.8o), Hausner ratio (1.16) and Carr’s compressibility index (13) for the 8% binder batch show excellent flow properties and is indicative of forming tablets with good qualities. “8% binder” tablets batch has the following properties; hardness (kgF), friability (0.55%), disintegration time (220 secs), all within the acceptable official requirements. The release profile showed that the drugs were bioavailable from the tablets in good time. It can be concluded that the formulation of an FDC for HTN-DM comorbidity was a success and studies to confirm the compatibility of the APIs and excipients are recommended.