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 61
- Downloads 0
Preparation, Characterization and Optimization of Poloxamer Solid Dispersions of a Poorly Water Soluble Drug Aprepitant
Aim: The aim of the present investigation was to enhance the dissolution rate of a poorly water soluble drug, aprepitant, by preparation of solid dispersion with hydrophilic carrier, poloxamer 188, using solvent evaporat...
The Protective Role of Extract of Allium cepa Linn. (Liliaceae) (Red Onion) Bulb in Artesunate-induced Testicular Damage in Male Wistar Rats
Aim: Allium cepa is consumed fresh or cooked in Nigeria and used as herb in ethno-medicinal practice against many ailments. The aqueous extract is used in the management of prostrate inflammation, alleviation of low sper...
Antimicrobial Activity of Camel’s Urine and Its Effect on Multidrug Resistant Clinical Bacterial and Fungal Isolates
Aims: The aim of this work is to study the In vitro antimicrobial effect of camel’s urine on a variety of multi-drug resistant bacterial and fungal isolates. Methodology: Agar dilution method was used to determine the ef...
Cytotoxic and Apoptotic Effects of the Bark of Two Common Mango (Mangifera indica) Varieties from Sri Lanka on Breast and Ovarian Cancer Cells
Aims: The present study was planned to evaluate cytotoxic and apoptotic properties of the bark of two common mango varieties (Mangifera indica L.) grown in Sri Lanka [Rata Amba (RA) and Karthakolomban (KA)] in MCF-7 (ER...
Pharmacist Perceived Barriers to Patient Counseling; A Study in Eastern Region of Saudi Arabia
Background: Pharmaceutical care model (PCM) is the philosophy of practice that includes identifying and resolving medication therapy problems to improve patient outcomes. Patient counseling by a pharmacist is a fundament...