FORMULTION AND EVALUATION OF CAPTOPRIL MOUTH DISSOLVING TABLETS

Ahmed Mohamed Othman, Mahmoud Mahyoob Alburyhi* and Ghada Hassan Al-Hadad

ABSTRACT

Pharmaceutical technologists have developed a novel oral dosage form known as Orally Disintegrating Tablets (ODTs) which disintegrate rapidly in saliva, usually in a matter of seconds, without the need to take water. Drug dissolution and absorption as well as onset of clinical effect and drug bioavailability may be significantly greater than those observed from conventional dosage forms. Captopril is a sulfhydryl-containing angiotensin-converting enzyme inhibitor which is the enzyme that converts angiotensin-I to angiotensin II and may also reduce the degradation of bradykinin. It is used in the management of hypertension, heart failure, myocardial infarction and in diabetic nephropathy. Therefore, it can be used as a model of mouth dissolving tablets as a more bioavailable form than conventional tablets. The objective in the present study was to formulate and evaluate of Captopril mouth dissolving tablets (MDTs) used antihypertensive drug. Several formulations of Captopril MDTs were prepared using the drug with the selected fillers (microcrystalline cellulose(avicel), lactose and mannitol) in addition to disintegrates (sodium starch glycolate (explotab) and croscarmellose sodium (Ac-di-sol) or effervescence agents (sodium bicarbonate & citric acid), glidant, sweetening agent and magnesium stearate as a lubricant (starch as a binder in some formulae). They were prepared by direct compression and wet granulation and compressed into tablets using a single punch machine equipped with 8.5mm concave punch. From these results it can be noted that formulae containing SSG or effervescence agents as disintegrants and Avicel PH101 as fillers (F1, F2, F3&F13) showed relatively higher dissolution, where 93.9%, 93.1%, 93.1% and 93 of the labeled dose were dissoluted after 5 minutes whereas 54.4%, 45.8% and 74.33% drug dissolution from marketed products (Captopril-Denk®, Capotal® 25 and Farcopril ®, respectively). Kinetic Analysis of the dissolution data of Captopril from different tablet formulations were determined using linear regression according to zero-order, first-order and Higuchi diffusion model, the coefficient of determination (R2) was determined in each case. The highest value of R2 yields the best fit. Therefore, predominant mechanism of Captopril MDTs was zero–order kinetics and only few were found to follow Higuchi diffusion model. It was concluded that F1 is the best formulation of prepared Captopril MDTs in order to increase onset of action and bioavailability of drug.

Keywords: Captopril, Mouth dissolving tablets, Disintegrates.