Abstract
Hypertension is one of the most common chronic cardiovascular disorders. Sustained-release formulations are developed to maintain drug therapeutic levels throughout the treatment of hypertension, to promote patient compliance and improve patient outcomes. We have developed and tested in in vivo trials a once-a-day tablet formulation for the novel antihypertensive drug MT-1207. The tablets based upon a hydrophilic polymer matrix underwent post-compression parameter and physicochemical characterisations, along with in vitro drug release testing. The most promising formulation containing 31% w/w HPMC K15M gave a 24-hour release of MT-1207 with an almost constant release rate up to 20 hours. Follow in in vivo studies were carried out in Beagle dogs for the optimised sustained-release tablets in comparison to immediate-release tablets. The results showed that a sustained release of MT-1207 from the new formulation was achieved with a drug t1/2 2–2.5 times longer than the immediate-release tablets. Moreover, the AUC0-24h values of both sustained- and immediate-release tablets were identical at the same dose of 30 mg, indicating that the same amount of drug was absorbed in each case. For treatments based upon MT-1207, this development is significant for future commercial exploitation via scale-up and further trials, and for improved patient outcomes.
Highlights
Hypertension is the most common cardiovascular disease, with 1.39 billion adults46 worldwide having the condition in 2010 (Katzung et al 2012; Mills et al 2016)
The results showed that a 35 sustained release of MT-1207 from the new formulation was achieved with a drug t1/2 2-2.5
MT-1207 was 438 more soluble in hydrochloric acid than in phosphate buffer (Table S1). Since the latter was chosen as the dissolution medium in the present study, a small amount of sodium dodecyl sulfate (SDS) was added into phosphate buffer to ensure sink conditions during dissolution testing
Summary
Hypertension is the most common cardiovascular disease, with 1.39 billion adults46 worldwide having the condition in 2010 (Katzung et al 2012; Mills et al 2016). Hypertension is the most common cardiovascular disease, with 1.39 billion adults. Hypertension presents a significant challenge in therapeutics as it is usually a 49 lifelong disease that causes few symptoms until its advanced stage. There is a need for 50 improved formulations that can make more effective use of current drugs, as even relatively. small improvements in factors such as patient compliance and therapeutic efficacy are important and would have a very significant impact on human health. 55 inhibitors, angiotensin II receptor antagonists, alpha-receptor antagonists, diuretics. It is mainly the level of blood pressure and the presence, and severity of, end organ damage that dictate the selection of a drug or drug combination for a patient.
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