ABSTRACT
The objective of the present study was to develop the mucoadhesive buccal film of valdecoxib for the treatment of oral sub mucous fibrosis, a localized buccal disease. Valdecoxib, a novel COX-2 inhibitor has been reported to be used in various osteopathic and rheumatoid conditions as oral therapy. The films were made out of chitosan and HPMC K4M as polymers. Sodium taurocholate was used as a permeation enhancer. All the formulations were examined for film thickness, swelling properties, drug content, weight variation, in vitro release studies, bioadhesive force, tensile strength, diffusion studies using pig mucosa and pharmacokinetic study in healthy male volunteers. Prepared films were thin, flexible, smooth and transparent. Bioadhesive force and tensile strength of the optimized formulation were found to be 75 +/- 4 kg m(-1) S(-2) and more than 2.5 kg/3 cm(2), respectively. The percent drug content was 98.5 +/- 1.3%. The in vitro drug release from the selected formulation showed that about 69.34% of the drug payload was released up to 6 hours. The drug permeation through the dialysis sac and pig buccal mucosa was found to be 62.70% and 54.39%, respectively. Pharmacokinetic studies of the buccal mucoadhesive film showed that the drug was released locally at the target site of action, and a very small amount might have absorbed systemically.
Subject(s)
Chitosan/chemistry , Cyclooxygenase Inhibitors/administration & dosage , Cyclooxygenase Inhibitors/pharmacokinetics , Drug Carriers/chemistry , Isoxazoles/administration & dosage , Isoxazoles/pharmacokinetics , Mouth Mucosa/metabolism , Oral Submucous Fibrosis/drug therapy , Sulfonamides/administration & dosage , Sulfonamides/pharmacokinetics , Adhesiveness , Administration, Buccal , Adult , Animals , Chitosan/administration & dosage , Cyclooxygenase Inhibitors/blood , Diffusion , Drug Carriers/administration & dosage , Humans , Hypromellose Derivatives , Isoxazoles/blood , Male , Methylcellulose/analogs & derivatives , Methylcellulose/chemistry , Sulfonamides/blood , Swine , Taurocholic Acid/chemistry , Tensile StrengthABSTRACT
The aim of this study was to develop an enteric-coated multiunit dosage form containing aceclofenac, a nonsteroidal anti-inflammatory drug. The pellets were prepared by using extrusion/spheronization method, and the core pellets were coated with a pH-sensitive poly(meth) acrylate copolymer (Eudragit L100-55) to achieve site-specific drug release. The formulated pellets were characterized for percentage yield, size distribution, surface morphology studies, drug content, and flow properties. In vitro dissolution test was used for comparison of drug release profiles of various coated pellets. The practical yield was found to be 90-95%. The particle size of enteric-coated pellets was found to be in the range of 0.59-0.71 mm. The pellets were spherical in shape and surfaces of pellets were found to be rough and showing micropores. Enteric-coated pellets showed good flow properties and in vitro dissolution profile. Dissolution tests were carried out in a USP type II dissolution apparatus in media-simulating pH conditions of the gastrointestinal tract. The release of the aceclofenac from formulated pellets was established to be minimum in the pH 1.2 (<5%) for a period of 2 h, and at pH 6.8, it shows the maximum release (85 +/- 5% release within 1 h) which indicates gastric resistance of the formulated pellets. The 20% wt/wt enteric-coated pellets were compared to that of marketed product (tablets), it was observed that pellets showed better release profile. The study concluded that the formulated multiparticulate dosage forms can be used as an ideal drug delivery system for the aceclofenac.