Biowaiver Eligibility of a Lower Strength Ramipril/Hydrochlorothiazide Immediate Release Tablets Using a New Validated HPLC Analytical Method

Abstract

Bioequivalence studies are expensive, time consuming and invasive to humans. Accordingly, an alternative in vitro study (biowaivers) has been introduced for drugs which belong to BCS class I and III and for other strengths of already approved higher drug strength. The main objective of this study was to prove the biowaiver eligibility of a lower strength Ramipril/Hydrochlorothiazide (2.5/12.5 mg) tablets. Visual and pharmacopoeial quality tests were performed on the higher and lower generic and on the reference listed drug to determine whether they are pharmaceutically equivalent. All products were investigated using the biowaiver criteria. Dissolution profiles were conducted at pH values 1.2, 4.5 and 6.8. Difference factor () and similarity factor () were calculated. The tested products were successfully complied with pharmacopeial requirements. was below 15 and was above 50 in all dissolution conditions. Precisely, Ramipril showed release higher than 85% within 15 min. and for Hydrochlorothiazide were 8 and 61 respectively at the recommended discriminative pH media.These results suggest that the current biowaiver criteria could be a sufficient guarantee of bioequivalence of the lower strength of Ramizide assuming that the product is manufactured at the same site and contains same quality and grade of excipients and in a proportional amounts.

A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products

“…While some authors have referred to HCTZ as a BCS class IV drug (high solubility, low permeability) (Ghadi and Dand, 2017;Löbenberg and Amidon, 2000;Sanphui et al, 2015), HCTZ, which has a pK a value of 7.9 (O'Neill, 2013) has been reported to have a solubility ranging from 60.8 mg to 103 mg per 100 ml within the pH range 1.0 to 7.4 (Blatnik et al, 2015). As the maximum daily dose of HCTZ is 100 mg (Brayfield, 2014), HCTZ may be considered highly soluble according to the BCS system, as the maximum dose dissolves in less than 250 ml water over the stated pH range, and it may thus be classed as a BCS class III (high solubility, low permeability) drug compound (Klein and Shah, 2008;Yu et al, 2004;Zaid et al, 2016).…”

“…RAM has a pK a value of 3.17 (O'Neill, 2013). The maximum daily dose of RAM is 10 mg (Brayfield, 2014) and, with a sparingly soluble (British Pharmacopoeia, 2018b) solubility in water, RAM is classified as a BCS class I (high solubility, high permeability) compound (Ramirez et al, 2010;Zaid et al, 2016). SD (Tajber et al, 2005) and HME (De Jaeghere et al, 2015;Dierickx et al, 2012;Vynckier et al, 2015Vynckier et al, , 2014 techniques have been previously successfully used to process HCTZ alone.…”

Formulation And Evaluation of Fast Dissolving Oral Films Incorporated With Ramipril and β-Cyclodextrin Complex

“…The analysis performed in triplicate for all the formulations. [16] Drug Excipient Compatibility Study by FTIR FTIR (Schimadzu IR Affinity 1 spectrophotometer) was used to record the FTIR spectra of pure ramipril and ramipril FDOF in 4,000 to 400 cm -1 range. [17]…”

Розробка І Валідація Методики Визначення Раміприлу Та Гідрохлортіазиду Для Вивчення Профілів Розчинення

“…Одночасне визначення раміприлу та гідрохлортіазиду описано в ряді публікацій [7][8][9][10], однак про можливість використання методики для різних середовищ розчинення ідеться лише в [10]. До того ж методики валідували у вузькому діапазоні, що дозволяло аналізувати лише одне дозування препарату, тоді як, відповідно до [11], на ринку України зареєстровано п'ять різних дозувань препарату.…”

“…У всіх проаналізованих публікаціях ідеться про використання колонки, заповненої октадецилсилільним сорбентом. Згідно з [8][9][10], як буферний компонент застосовували розчин перхлорату натрію концентрацією від 12 до 14 г/л, як органічний компонент -ацетонітрил. Тривалість інжекції, відповідно до [8], становила близько 20 хв, згідно з [9, 10] -приблизно 10 хв, що є досить тривалим.…”