Development and evaluation of fixed dose bi therapy sublingual tablets for treatment stress hypertension and anxiety

Abstract

Objective:A stress induced rise in the blood pressure. Some believe that patients with hypertension are characterized by a generalized state of increased anxiety.Aim:The purpose of this study is to prepare a fixed dose bi therapy using bisoprolol hemifumarate (BH) as antihypertensive drug and buspirone hydrochloride (BuHCl) as anxiolytic drug, which can be used to treat both diseases concomitantly. Using sublingual tablets is hopeful to improve the BuHCl poor oral bioavailability and to facilitate administration to patients experiencing problems with swallowing.Materials and Methods:A total of 5mg BH and 10mg BuHCl were selected based on compatibility study. A 3×22 full factorial design was adopted for the optimization of the tablets prepared by direct compression method. The effects of the filler type, the binder molecular weight, and the binder type were studied. The prepared formulae were evaluated according to their physical characters as hardness, friability, disintegration time (new modified method and in vivo disintegration time) and wetting properties. In vitro drugs dissolute, permeation through the buccal mucosa and the effect of storage were analyzed by a new valid high pressure liquid chromatography (HPLC) method. Bioavailability study of the selected formula study was carried out and followed by the clinical.Results:The optimized tablet formulation showed accepted average weight, hardness, wetting time, friability, content uniformity, disintegration time (less than 3 min). Maximum drug release could be achieved with in 10 min. In addition enhancing drug permeation through the buccal mucosa and, the maximum concentration of the drug that reached the blood was in the first 10 min which means a rapid onset of action and improved the extent of both drug's absorption.Conclusion:The results revealed that sublingual (F6) tablets containing both drugs would maintain rapid onset of action, and increase bioavailability. BuHCl with BH can be attributed to the marked decline in DBP and SBP. That led to a reduction in the MAP.

Enhanced Transdermal Delivery of Bisoprolol Hemifumarate via Combined Effect of Iontophoresis and Chemical Enhancers: Ex Vivo Permeation/In Vivo Pharmacokinetic Studies

“…This is in addition to its ability to emulsify sebum, allowing higher power of drug penetration into the skin as previously mentioned. Similar results were obtained by Nabarawi et al in their study on transdermal delivery of BH, where Tween ® 80 changed the skin’s barrier properties [ 4 ], allowing for enhanced transdermal permeation. It is worth to note that Tween ® 80 is among the widely used and pharmaceutically acceptable permeation enhancers used for transdermal delivery of a wide variety of drug actives.…”

“…Bisoprolol hemifumarate (BH), chemically known as 1-[4-(2-isopropoxyethoxymethyl) phenoxy]-N-isopropyl-3-aminopropan-2-ol fumarate, is a selective β1 receptor blocker [ 3 ]. It is used as a first-line treatment for hypertension, angina pectoris and congestive heart failure [ 4 , 5 ]. As reported by Nabarawi et al, BH has led to 46% reduction in sudden death of treated patients after almost one year of treatment [ 4 ].…”

“…It is used as a first-line treatment for hypertension, angina pectoris and congestive heart failure [ 4 , 5 ]. As reported by Nabarawi et al, BH has led to 46% reduction in sudden death of treated patients after almost one year of treatment [ 4 ]. Immediate release tablets are also characterized by rapid absorption and reduced hepatic first pass metabolism resulting in an oral bioavailability reaching almost 90% [ 3 , 5 ].…”