ex vivo permeation

The present study is concerned with formulation and evaluation of mucoadhesive buccal patches containing antihypertensive drug i.e. Timolol to avoid the first pass effect and to improve its bioavailability with reduction in dosing frequency and also dose related side effects. The patches were prepared by solvent casting technique with varying concentration of HPMC E15 as polymer and propylene glycol as the plasticizer and evaluate their physicochemical properties, in vitro drug release, moisture absorption, surface pH, mechanical properties, in vitro bio adhesion, and ex vivo drug permeation through porcine buccal membranes from optimized buccal patch. The physicochemical interaction between timolol and polymer was investigated by Fourier transform infrared spectroscopy. Moisture absorption, surface pH, tensile strength, elongation at break, peak detachment force and work of adhesion values of the optimized formulation F4 were found to be 124±10.59%, pH 6.61±0.28, 3.89 kg/mm2, 14.16 mm2, 4.92±0.06N and 0.65±0.08mJ respectively. Formulation F4 showed 68.99 ±1.67% of the drug release in in vitro condition and follows zero order kinetics and drug release mechanism follows non-fickian diffusion. Ex vivo drug permeation through porcine buccal membrane was performed and 58.52±1.59% of the drug permeated in 6 hrs with flux 0.22 mg/h/cm2.The optimized formulation F4 with permeation enhancer tween 80 (1% v/w) showed drug release 64.47±1.63 % in 6 hrs with flux 0.33mg/h/cm2. FTIR studies showed no evidence of interaction between the drug and polymers. Drug release from the buccal patches follows desire controlled release phenomenon as required in mucoadhesive drug delivery.

  Promethazine Hydrochloride (PMZ), a low bioavailabe drug, used for the management of emesis. The purpose of the present investigation was to develop buccoadhesive tablets for PMZ and to evaluate for their physicochemical, in vitro, ex vivo and in vivo parameters. Ex vivo drug permeation through porcine buccal membrane from the drug solution was conducted to know the permeation characteristics of the PMZ. The controlled-release PMZ tablets were produced by direct compression method using Sodium CMC and Carbopol 934P as mucoadhesive polymers and evaluated for in vitro drug release, in vitro bioadhesion, in vivo residence time, swelling and erosion studies, surface pH, ex vivo drug permeation through porcine buccal membrane from the optimized buccal tablet (F10) and stability studies. Formulation F10 showed maximum drug release (96.3 %) in 6 h, with the Higuchi model release profile and permeated 49.8 % of the drug with flux 1.45 mg h–1cm–2 through porcine buccal membrane. The optimized formulation showed peak detachment force (1.64 N), work of adhesion (0.36 mJ), in vivo residence time (287 min), swelling index (204%), erosion (53.1%) and surface pH (6.92). In vivo mucoadhesive behaviour of the optimized formulations was studied in healthy human volunteers and subjective parameters were evaluated. The stability of the optimized formulation was studied and no significant changes were detected in drug content and in vitro release after 6 months. PMZ mucoadhesive tablets for buccal delivery could be prepared with required permeation, bioadhesive and in vivo residence properties.