Formulation of oxybutynin chloride microparticle-loaded suppositories: in vitro characterization and in vivo pharmacokinetic study

Abstract

BackgroundOxybutynin chloride (OXC) is used to treat overactive urinary bladder. OXC is metabolized in the liver to N-desethyloxybutynin, which is mainly responsible for the anticholinergic side effects of OXC. Conventional oxybutynin suppositories formulated earlier have shown most common side effects, such as dry mouth, constipation and serious anticholinergic reaction. Hence the present research work deals with the formulation and characterization of OXC microparticle-loaded mucoadhesive suppositories which may remain adhered in the lower rectum and avoid first pass metabolism. The emulsification–ionic gelation method is employed to prepare OXC microparticles. Two formulation factors at three levels, i.e. polymer concentration and stirring speed, were selected. Sodium alginate (concentration 1–2%) and 1% w/v Carbopol 971P were used to prepare OXC microparticles. OXC microparticles were evaluated for various parameters such as production yield, entrapment efficiency, mucoadhesive strength, shape, size, zeta potential, Fourier Transform Infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, in vitro dissolution studies and stability studies. Suppositories loaded with OXC microparticles were prepared by the fusion method using Poloxamer 188 and propylene glycol and evaluated for various parameters like weight variation, disintegration time, in vitro dissolution study, stability study and pharmacokinetic study.ResultsResults of in vitro characterization revealed that optimized batch of OXC loaded microparticles exhibited production yield 94.024% entrapment efficiency 95.378% and mucoadhesion strength 95.544%, particle size range 764.04–894.13 µm, zeta potential − 14.5 mV, with 0.946 desirability. Consequences of DSC and XRPD evaluation shown that drug was effectively entrapped inside the microparticles. In vitro release studies revealed improvement in drug dissolution as a consequence of its entrapment into microparticles. SEM results showed that micelles were sphere-shaped. On rectal administration of OXC microparticles loaded suppository in male Sprague–Dawley Rats, the relative bioavailability was found 173.72%.ConclusionIn vivo study elicits rapid increase in absorption of drug from microparticles loaded suppository when compared with the oral formulation and drug loaded suppository in rats. OXC microparticles loaded suppository is novel and promising drug delivery system for rectal administration and may avoid anticholinergic side effects of hepatic metabolite, N-desethyloxybutynin. These rectal drug delivery systems will be advantageous for efficient absorption of drugs and to avoid first pass metabolism.