Laboratory-scale development of an over-the-counter famotidine formulation
Olivier, Terri Gaynor
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The laboratory-scale development of an over-the-counter (O.T.C.) 10mg famotidine tablet is described. A literature review and drug-excipient compatibility studies conducted at Potchefstroom University for Christian Higher Education (P.U. for C.H.E.) represented the initial reformulation development stage. Physicochemical properties of famotidine pertinent to the formulation of a stable and bioavailability dosage form were elucidated : poor aqueous solubility (Budavari, 1989:617); poor lipophylicity (Islam & Narurkar, 1993:686); photosensitivity (McEvoy, 1995:2029); susceptibility to gastric degradation (Guvener & Ates (1988:142); and interactions between famotidine and Kollidon, Primojel, Crospovidone, Emdex, Emcompress, lactose, sorbitol or stearic acid as reported by Indrayanto et al. (1994:911) and/or determined by P.U. for C.H.E. The performance of five direct compression excipients viz. Zeparox spray-dried lactose, Sorbitol Instant FG, Avicel pH 102 (microcrystalline cellulose) , Emdex (dextrates, NF hydrate) and Emcompress (dibasic calcium phosphate dehydrate), in a tablet containing 10mg of famotidine and 1% of magnesium stearate , as lubricant, was subsequently evaluated. The influence of the diluents on selected physical properties of the powder blend and of the tablets was assessed. The direct compression excipients which performed most favorably were then selected and three model formulations were derived, with the addition of Explotab (sodium starch glycolate), as disintegrate, to enhance bioavailability. The first formulation comprised 10mg of famotidine, 8mg of Explotab, 180mg of Zeparox spray-dried lactose and 2mg of magnesium stearate per tablet. The second formulation contained 10mg of famotidine, 4mg of Explotab, 40mg of Avicel, 144mg of Emcompress and 2mg of magnesium stearate per tablet; while, the third included 10mg of famotidine, 2mg of Explotab, 166mg of Avicel and 2mg of magnesium stearate. These formulations were produced on a laboratory scale, using a Manesty F3 single punch tablet press, and were subjected to three months preliminary accelerated stability testing in polypropylene securities. Conditions of 40°C ±2°C and 75% ±5% relative humidity were maintained in a Gallenkamp environmental chamber. The second formulations failed accelerated stability testing; while, the first and third were found to be acceptable. The first formulation; however, demonstrated a reduction in famotidine assay and slight brown discolorations over the three months test period. The third formulation is therefore recommended. Further investigations suggested in the development of alternative O.T.C. formulations include enteric coating to eliminate gastric degradation (Güvener & Ates, 1988:142) and the use of melt extrusion technology (Grünhagen & Mülller, 1995:167) to improve bioavailability and/or reduce production costs.
- Health Sciences