Development and evaluation of oral solid dosage forms for colonic delivery of drugs for the treatment of cystinosis.
Ibie, Chidinma O.
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Modified release multiparticulate pellets have been produced by the process of extrusion and spheronisation for colon-targeted delivery of cystamine, a cysteamine derivative. Orally ingested cysteamine formulations used in the treatment of cystinosis, are observed to cause gastrointestinal mucosa irritation leading to nausea, vomiting and ulceration in patients on such therapies. Spheronised pellets were prepared varying the type and concentration of the polymer used as an extrusion aid in the formulation. Classes of polymeric materials tested include starches, natural gums and cellulose derivatives. The properties of each wet mass formulation, extrudate and spheronisation product obtained were subsequently evaluated and compared to that obtained from a standard extrusion aid, microcrystalline cellulose. Viable pellets produced were subjected to detailed analytical procedures that include: pellet size analysis, qualitative sphericity determination, friability testing, bulk density measurements, optical and scanning electron microscopy. Amongst the polymers tested, blends of 60/40% and 65/35% low/high acyl gellan gum (Kelcogel®) incorporated into lactose-based wet masses produced good pellets with relatively high sphericity (percentage sphericity: 65-70%). Cystamine was subsequently incorporated into gellan and microcrystalline cellulose pellets and efforts made to tailor the release profile of the drug by coating pellets with Eudragit® FS30D, a pH-sensitive polymer. The dosage forms described should selectively deliver the drug to the colon through pH-dependent dissolution of the polymer coating at colonic pH conditions (pH 7.4) thereby minimising the incidence of any gastrointestinal side effects. Dissolution results showed that Eudragit® FS30D coated cystamine pellets released < 3% of incorporated drug in 0.01M HCl over 1 hour at gastric pH of 1.2, while > 90% of the drug was released in phosphate buffer at pH 7.4. Indicating the suitability of these coated pellets as potential colon-targeted dosage forms for delivery of cysteamine.