RESUMO
Resealed erythrocytes, as drug delivery system has tremendous potential to achieve site specificity and prolonged release of drug thereby enhancing therapeutic index and patient compliance. In the present investigation erythrocytes obtained from healthy volunteers were loaded with prednisolone using preswell dilution and dilution technique with two different cross-linking agents, glutaraldehyde and dimethylsulphoxide. Carrier erythrocytes, having acceptable loading parameters showed increased percentage drug content with the addition of cross-linking agents. In vitro drug release followed zero-order kinetics, haemoglobin content was found to be satisfactory and osmotic fragility study indicated that increased drug entrapment efficiency was found at 0.3%w/v concentration of sodium chloride (hypotonic solution). In vivo tissue distribution studies were carried out for optimized formulation and order of distribution was found to be Liver>Lung>Kidney> Spleen. The developed drug delivery system is endowed with several exclusive advantages and hence holds potential for further research and clinical application.
Assuntos
Portadores de Fármacos/farmacocinética , Composição de Medicamentos/métodos , Eritrócitos/química , Prednisolona/administração & dosagem , Prednisolona/farmacocinética , Reagentes de Ligações Cruzadas/química , Dimetil Sulfóxido/química , Portadores de Fármacos/química , Avaliação Pré-Clínica de Medicamentos , Eritrócitos/citologia , Eritrócitos/metabolismo , Glutaral/química , Hemoglobinas/metabolismo , Humanos , Técnicas In Vitro , Fragilidade Osmótica , Pressão Osmótica/efeitos dos fármacos , Distribuição TecidualRESUMO
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.