| Abstract: |
The present investigation was initiated with an ultimate goal of promoting the solubility and dissolution of acetazolamide and hydrochlorothiazide. The selected drugs, acetazolamide and hydrochlorotluazide, are commonly employed as diuretics .Acetazolamide is a carbonic anhydrase inhibitor, which acts mainly by reducing the rate of interaction between water and carbon dioxide, thereby reducing the availability of hydrogen ions and resulting in the excretion of an increased amount of sodium and bicarbonate. Hydrochlorothiazide is a member of the benzothiadiazine class, it acts mainly by .inhibiting reabsorption of electrolytes from the proximal part of the distal renal tubule, thereby increasing the excretion of sodium, potassium and chloride ions, and consequently of water.The limited solubility of both drugs limits their dissolution prior to their absorption and, hence, could limit their bioavailability upon administration.In the present investigation, some techniques have been applied for the improvement of the solubility and dissolution of both drugs, viz. : cyclodextrin complexation, solid dispersion ,.and crystallization from solutions of hyDROPhilic macromolecules. Additionally, in each case the most suitable technique was chosen for formulation of tablet dosage form. Furthermore, the release characteristics and pharmacological activity of the prepared systems of each drug were investigated.As an integral part of the-work, attempts were made to discuss the main mechanism(s) responsible for the dissolution rate improvement and to shed some light on the mechanism of interaction of both drugs with some macromolecules in the solid and liquid slates.
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