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Abstract. The aim of this study was to investigate the combined influence of three independent variables on the permeation kinetics of lisinopril from hydrogels for transdermal delivery. A three-factor, threelevel Box-Behnken design was used to optimize the independent variables, Carbopol 971 P (X 1 ), menthol (X 2 ), and propylene glycol (X 3 ). Fifteen batches were prepared and evaluated for responses as dependent variables. The dependent variables selected were cumulative amount permeated across rat abdominal skin in 24 h (Q 24 ; Y 1 ), flux (Y 2 ), and lag time (Y 3 ). Aloe juice has been first time investigated as vehicle for hydrogel preparation. The ex vivo permeation study was conducted using Franz diffusion cells. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the cumulative permeation of LSP in 24 h (Q 24 ) was Y 1 =1,443.3-602.59X 1 +93.24X 2 +91.75X 3 − 18.95X 1 X 2 -140.93X 1 X 3 -4.43X 2 X 3 -152.63X 1 2 -150.03X 2 2 −213.9X 3 2 . The statistical validity of the polynomials was established, and optimized formulation factors were selected by feasibility and grid search. Validation of the optimization study with 15 confirmatory runs indicated high degree of prognostic ability of response surface methodology. The use of Box-Behnken design approach helped in identifying the critical formulation parameters in the transdermal delivery of lisinopril from hydrogels.

Bilayered mucoadhesive buccal patches for systemic administration of domperidone (DOM), a dopamine-receptor (D(2)) antagonist, were developed using hydroxy propyl methyl cellulose and PVPK30 as a primary layer and Eudragit RLPO and PEO as a secondary layer. Ex vivo drug permeation through porcine buccal membrane was performed. Bilayered buccal patches were developed by solvent casting technique and evaluated for in vitro drug release, moisture absorption, mechanical properties, surface pH, in vitro bioadhesion, in vivo residence time and ex vivo permeation of DOM through porcine buccal membrane from a bilayered buccal patch. Formulation DB4 was associated with 99.5% drug release with a higuchi model release profile and 53.9% of the drug had permeated in 6 h, with a flux of 0.492 mg/h/cm(2) through porcine buccal membrane. DB4 showed 5.58 N and 3.28 mJ peak detachment force and work of adhesion, respectively. The physicochemical interactions between DOM and the polymer were investigated by differential scanning calorimetry (DSC) and fourier transform infrared (FTIR) Spectroscopy. DSC and FTIR studies revealed no interaction between drug and polymer. Stability studies for optimized patch DB4 was carried out at 40°C/75% relative humidity. The formulations were found to be stable over a period of 3 months with respect to drug content, in vitro release and ex vivo permeation through porcine buccal membrane. The results indicate that suitable bilayered mucoadhesive buccal patches with desired permeability could be prepared.

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Buccal delivery of drugs provides an attractive alternative to the oral route of drug administration, particularly in overcoming deficiencies associated with the latter mode of administration. Problems such as high first-pass metabolism and drug degradation in the harsh gastrointestinal environment can be circumvented by administering the drug via the buccal route (1-3). Moreover, buccal drug absorption can be promptly terminated in case of toxicity by removing the dosage form from the buccal cavity. It is also possible to administer drugs to patients who cannot be dosed orally to prevent accidental swallowing. Therefore adhesive mucosal dosage forms were suggested for oral delivery, which included adhesive tablets (4-6), adhesive gels (7, 8) and adhesive patches (9, 10). Buccoadhesive tablets of carvedilol were prepared using HPMC K4M, HPMC K15M and Carbopol 934 as mucoadhesive polymers. Fifteen formulations were developed with varying concentrations of polymers. Formulations of the BC or BD series were composed of HPMC K4M or HPMC K15M in ratios of 1:1 to 1:5 whereas in the BE series Carbopol 934 was used (1:0.25 to 1:1.50). The formulations were tested for in vitro drug release, in vitro bioadhesion, moisture absorption and in vitro drug permeation through porcine buccal mucosa. Formulation BC3 showed maximum release of the drug (88.7 ± 0.4%) with the Higuchi model release profile and permeated 21.5 ± 2.9% of the drug (flux 8.35 ± 0.291 µg h -1 cm -2 ) permeation coefficient 1.34 ± 0.05 cm h -1 ) through porcine buccal membrane. BC3 formulation showed 1.62 ± 0.15 N of peak detachment force and 0.24 ± 0.11 mJ of work of adhesion. FTIR results showed no evidence of interaction between the drug and polymers. XRD study revealed that the drug is in crystalline form in the polymer matrix. The results indicate that suitable bioadhesive buccal tablets with desired permeability could be prepared.