Timolol

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.

The purposes of the present study were: 1).To study the relationship between different concentrations of the chiral enhancer D-Limonene (D-LM) on the solubility of individual enantiomer and racemate Timolol maleate (TM). 2). To study the preferential enhancement of D-LM upon S-TM, R-TM, and racemate across the hairless mice skin. For solubility studies, excess of R-, S-, or racemate with wide-range of different concentrations of D-LM were prepared.  Samples were agitated, centrifuged and filtered and analyzed by HPLC using chiral column at 294nm.  For skin transport studies, formulations containing 0.5% solutions of S-TM, R-TM, or racemate in buffer solution with predetermined concentrations of D-LM were studied. Samples of 1-ml were withdrawn and quantitatively analyzed for their TM contents.  The steady-state fluxes (Jss), permeability coefficients and the enhancement factor were calculated. In solubility studies, D-LM significantly enhances solubility of all forms of TM in a concentration dependent manner.  In permeation studies, presence of D-LM significantly enhances the flux values of both enantiomers and racemate.  However, D-LM immensely increased all permeability characteristics of the S-isomer compared to those of R-isomer. Solubilities of all forms of TM were found to be a single-valued function of D-LM concentration. Moreover, addition of D-LM has enhanced the transport of S-, R-TM enantiomers and that of racemate across hairless mice skin.  For all tested formulations, the overall permeability characteristics of the therapeutically active TM (i.e., S-TM) were superior results obtained with the R-TM either as enantiomer or racemate.

  Beta-blockers are the first line drugs in lowering the elevated and normal intraocular pressure associated with neuropathy of glaucoma, but for many reasons the use of this group of drugs requires supportive medications. The systemic side effects due to overdose of these drugs leads to pathetic complications in patients suffering with cardiac and pulmonary diseases. This article provides necessary information for the safe use of beta-blockers with detailed information about the disease glaucoma. Recent advances in the glaucoma therapy with beta-blockers and novel drug delivery systems developed are reviewed in this study.   Key words: Glaucoma, beta-blockers, intraocular pressure, Timolol, Levobunolol