ABSTRACT
Currently cocrystals are considered as an established approach for making crystalline solids with overall improved physico-chemical properties. However, some otherwise well behaving cocrystals undergo rapid dissociation during dissolution, with ultimate conversion to parent drug and thus apparent loss of improved solubility. The polymeric carriers are long known to manipulate this conversion during dissolution to parent crystalline drug, which may hinder or accelerate the dissolution process if used in a dosage form. The goal of this study was to deliver in vivo a more soluble carbamazepine-succinic acid [CBZ-SUC] cocrystal in suspension formulation utilizing Hydroxypropyl methyl cellulose [HPMC-AS] as a crystallization inhibitor and Polyvinyl carpolactam-polyvinyl acetate-polyethylene glycol graft co-polymer® as solubilizer. The concentration of these polymers were systemically varied during in vitro dissolution studies, while selected formulations from dissolution studies were tested in vivo. Pharmacokinetic studies [PK] in rabbits demonstrated that formulation F-X [1% cocrystal, 1% HPMC-AS and 2% Polyvinyl carpolactam-polyvinyl acetate-polyethylene glycol graft co-polymer caused almost 6fold improvement in AUCo-72 as well as much higher C[MAX] of 4.73microg.mL[+1] to that of l.OTmicrog.mL[+1] of unformulated 'neat' cocrystal given orally. When reference formulation of CBZ [F5-X] with similar composition to F-X were given to rabbits, cocrystal formulation gave 1.37fold bioavailability than CBZ reference formulation. C[MAX] of reference formulation observed was 3.9microg.mL