عنوان

Solubility and stability characterization of famotidine:

Number

TLpq304008518

.Language of Text, Soundtrack etc

انگلیسی

Title Proper

Solubility and stability characterization of famotidine:

General Material Designation

[Thesis]

First Statement of Responsibility

M. S. Islam

Title Proper by Another Author

Implications in the formulation of a solution dosage form

Subsequent Statement of Responsibility

M. M. Narurkar

Name of Publisher, Distributor, etc.

Northeast Louisiana University

Date of Publication, Distribution, etc.

1992

Specific Material Designation and Extent of Item

174

Dissertation or thesis details and type of degree

Ph.D.

Body granting the degree

Northeast Louisiana University

Text preceding or following the note

1992

Text of Note

A complete characterization of the physicochemical characteristics of famotidine is lacking in the literature. Although famotidine is commercially available in tablet, powder for suspension and intravenous injection forms, no oral solution dosage form is yet available. Also, the available liquid dosage forms, i.e., the reconstituted suspension and the injection, have inadequate stability at room temperature. The goal of this research project was to develop and evaluate a 10 mg/mL solution of famotidine which will be stable at 25C for 2 years. Studies were undertaken to determine the pH-dependence of aqueous solubility of famotidine (at 23 0.2C). A sigmoidal pH-solubility profile with higher famotidine solubility at lower pHs was observed. Stability of famotidine at different pHs was also investigated in different buffer solutions at an ionic strength of 0.5. The observed rate constants for famotidine degradation were in agreement with the predicted values, and famotidine was found to have a maximum solution stability at pH 6.5 0.25. pH dependence of the octanol/water partition coefficient of famotidine was studied at 23 0.2C. The pKa of famotidine calculated from the pH-solubility and pH-partitioning profile was found to be 6.98 and 6.89, respectively. A thermodynamic pKa of 6.69 (at 23 0.2C) for famotidine was determined by spectrophotometry. Phase-solubility studies using 2-hydroxypropyl-usd\betausd-cyclodextrin (HPCD) in pH 7.4 phosphate buffer, and solubilization experiments with different organic cosolvents were undertaken to investigate the feasibility of formulating a solution dosage form. HPCD afforded an approximately tenfold increase in solubility with various cosolvents improving the aqueous solubility of famotidine to different extents. At pH 2.02 and 37 0.5C, HPCD alone afforded an approximately 22-fold increase in famotidine stability. Stabilizing effect of various cosolvents and/or HPCD was studied at pH 6.5 0.25 and 37 0.5C; a blend of 20% propylene glycol (PG), 20% dimethylacetamide (DMA) and 60% phosphate buffer afforded the highest stability at 37 0.5C. The extent of hemolysis of rat erythrocytes at 25 0.5C by various components of the representative famotidine formulation was determined. PG (20%) had higher hemolytic potential than either 20% DMA or phosphate buffer alone. A famotidine solution (10 mg/mL) containing DMA and PG yielded a projected shelf-life (at 25C) of 1.6 years. Comparative bioavailability studies in male Sprague-Dawley rats revealed a significant increase in oral bioavailability of the solution formulation relative to a suspension.

Health and environmental sciences

Pharmaceuticals

M. M. Narurkar

M. S. Islam

Electronic name

p

[Thesis]

276903

a

Y