Design and Evaluation of a New Fixed-Dose Immediate Release Capsule of Atenolol, Enalapril Maleate and Hydrochlorothiazide
Journal Title: Journal of Pharmaceutical Research International - Year 2017, Vol 20, Issue 1
Abstract
Aim and Objectives: To design, formulate and perform in vitro studies of a fixed dose combination (FDC) immediate release solid dosage form of the antihypertensive drugs atenolol, enalapril and hydrochlorothiazide. The objectives of the study were to perform pre-formulation studies, design an immediate-release FDC capsule dosage form, and evaluate the prepared dosage form. Methods: Differential Scanning Calorimetric (DSC) analysis of physical mixtures of drugs and drug-excipient combinations was used to assess compatibility. Binary mixtures of atenolol and enalapril form a eutectic mixture indicating that a tablet dosage form, in which the drugs would be highly compressed together, may not be stable. Hard gelatin shell encapsulation was therefore employed. Atenolol and enalapril were separately dry-granulated with hydrochlorothiazide and excipients and mixed together at appropriate therapeutic proportions and encapsulated in size 1 hard gelatin capsules (HGC). Preliminary screening produced five formulations each with similar proportions of the 3-drug FDC but with 5 different levels of disintegrant. Capsule weight variation, disintegration time and dissolution rate were determined as output variables, following USP procedures. For the dissolution studies, a reverse phase high-pressure liquid chromatographic (RP-HPLC) method was developed for simultaneous analysis of the three drugs. Results: Granules possessed good fluidity (compressibility index 8.53 to 11.63 and tapped bulk density 1.09 to 1.132). Capsule disintegration time was generally 2 minutes while 80% of each drug dissolved within 20 minutes. Capsules showed no sign of physical instability or adverse effect during a period of 1 year shelf storage at room temperature (average temperature 25°C). Conclusions: Granules possess adequate fluidity and compressibility for filling into HGC. Results generally indicated that an immediate release FDC capsule of atenolol, enalapril and hydrochlorothiazide was stable for more than 1 year of observation. Capsule disintegration time and dissolution rate were generally within the USP specification.
Authors and Affiliations
Nickania A. Pryce, Amusa S. Adebayo, Deon A. Bennett, Eugenie Brown-Myrie
Keywords
Related Articles
- EP ID EP313121
- DOI 10.9734/JPRI/2017/38019
- Views 81
- Downloads 0
Preliminary Efficacy Assessment of Some Selected Indigenous Plant Species of Adamawa State, Nigeria on Salmonella typhi
Aims: To screened for phytochemicals and determine the in-vitro efficacy of the plants extracts on Salmonella typhi. Study Design: Phytochemicals and in-vitro efficacy assessment of seven medicinal plants in comparison t...
Knowledge and Practice of Prevention of Mother-To-Child-Transmission of HIV among Traditional Birth Attendants Practicing in Akwa Ibom, Nigeria
Background: Transmission of HIV from mother to child is by far the most common route of HIV infection in children. It is estimated that without effective interventions, between 67,500 and 125,000 infants will be infected...
Cardioprotective Effect of Tanopati against Doxorubicin-induced Myocardial Toxicity in Wistar Rats
Aim: The objective of this study was to determine the preventive role of Tanopati against doxorubicin induced myocardial toxicity in rats. Study Design: Randomized experimental controlled study. Place and Duration of St...
Diclofenac-induced Gastric Ulceration in Rats: Protective Roles of Pantoprazole and Misoprostol
Gastrointestinal damage caused by diclofenac remains a significant clinical problem. Pantoprazole provides potent and long-lasting inhibition of gastric acid secretion and has proven efficacy in healing diclofenac-associ...
Antimicrobial Activity of Ethanolic Crude Extracts of Thespesia populnea Flowers
Aim: To analyze the antimicrobial activity of ethanolic crude extract of Thespesia populnea Flowers. Study Design: Antimicrobial activity of Thespesia populnea was carried out using disc diffusion method against crude ex...