β-cyclodextrin-kneaded Coccinia grandis thermosensitive mucoadhesive buccal gel: factorial optimization and preclinical evaluation in cisplatin-induced pica.

To develop and optimize a Coccinia grandis (L.) Voigt root extract-loaded thermosensitive mucoadhesive buccal gel as a preclinical approach for antiemetic delivery. Thermosensitive gels containing an extract-β-cyclodextrin kneaded preparation were prepared using Poloxamer 407 and Carbopol 934P. Apparent solubility of the kneaded preparation was compared with that of the untreated extract. A 32 factorial design optimized polymer concentrations based on ex vivo permeation, mucoadhesive strength, and gelation temperature. The optimized formulation was evaluated for physicochemical properties, ex vivo permeation, stability, and anti-pica activity in a cisplatin-induced pica rat model. Kneaded preparation showed higher apparent solubility than the untreated extract. FTIR indicated compatibility between the extract and formulation components, but did not definitively confirm inclusion complex formation. BIG-F3 (Poloxamer 407, 19% w/v; Carbopol 934P, 0.22% w/v; desirability 0.989) exhibited gelation at 31.7 ± 0.3 °C, extract content of 94.5 ± 1.0%, and mucoadhesive strength of 4516 ± 105 dynes/cm2. Sustained transmucosal permeation was observed (84.03 ± 0.76% at 8 h; flux 393.69 ± 6.11 µg/cm2/h). BIG-F3 remained stable under refrigeration for six months. Buccal administration attenuated cisplatin-induced pica-like behavior, reducing Day 7 kaolin intake to 81.38 ± 6.30 mg/day versus 484.80 ± 14.97 mg/day in disease controls. BIG-F3 demonstrated improved apparent solubility, sustained transmucosal permeation, and preclinical anti-pica activity. Its effects were of similar magnitude to standard antiemetics on the rodent surrogate endpoint but do not establish therapeutic or clinical equivalence. Further physicochemical, in vivo pharmacokinetic, safety, and clinical studies are required.