Effect Of Formulation Variables On Availability Of Hydrochlorothiazide from Rectal Suppositories

The present investigation was initiated with an ultimate goal of enhancement of hydrochlorothiazide (HCT) release from suppositories to provide a convenient dosage form for infants and elderly patients. The selected drug, hydrochlorothiazide is employed as diuretic. Hydrochlorothiazide is a member of benzothiadiazine class, it acts mainly by inhibiting reabsorption of electrolytes from the proximal tubule, thereby increasing the excretion of sodium, potassium and chloride ions, and consequently of water. The limited solubility of the drug limits its dissolution prior to its absorption and hence, could limit its diuretic activity upon administration.In the present investigation, the dissolution and release rate of the drug from suppositories was enhanced by different methods and different additives. Crystallization and co-evaporation were used as techniques for preparation of drug additive adducts. Additionally the .most suitable technique was chosen for formulation of suppository dosage form. Furthermore, the release characteristics and pharmacological activity of the prepared systems were investigated. Thus, the thesis comprises the following chapters: .1- Formulation of Hydrochlorothiazide Using Different Suppository Bases.2- Effect of Different Additives on The Release Rate of Hydrochlorothiazide from Selected Suppository Bases.3- Effect of Formulation Variables on The Release Rate of Hydrochlorothiazide from Selected Suppository Bases.4- Pharmacological and Histological Studies