Film-coating of chitosan onto propranolol hydrochloride tablets: approach to fast and extended drug releases

Abstract

Cast films of chitosan acetate, citrate, formate, glcolate, lactate,malate and propionate containing acid : glucosamine unit at mole ratio of 1.2 : 1 were fabricated by solvent evaporation. From FT-IR, DSC and solid state ¹³C NMR studies, there was an evidence of amide formation and esterification in chitosan salt films after moist heat treatment at 60℃ 75%RH and dry heat treatment at 130℃ respectively. The decrease in hydrophilic groups after amide formation and esterification led to the decrease in water sorption and dissolution of heat treated films. Water sorption and dissolution of chitosan acetate and propionate films after moist heat treatment were very low whereas those of chiosan citrate and malate films were still quite high. Thus the former two films after heat treatment were release coated tablet. Propranolol HCI encapsulated in core tablet was used as model drug. Effect of various plasticizers, colorants and opaquants on compatibility with chitosan solutions or mechanical and abdesion properties of chitosan film was investigated. Propylene glycol, brilliant blue or green FS and talcum at concentration of 25, 0.5 and 15% w/w respectively were proved as a suitable plasticizer, colorant and pigment for the chitosan citrate film. Owing to aqueous soluble and rapidly disintegrating properties, good adhesion and long term aging stability, chitosan citrate seemed potentially to be utilized for the film coating approaching to fast release. Brilliant blue affected drug release behavior less than green FS and could provide enough tinctorial strength for coloring. Addition of propylene glycol 25% and low amount of talcum could improve mechanical properties. Talcum could potentially reduce moisture sorption and provide desired glossiness of film coat. Moist heat treatment at 60℃ 75% RH was more effective than that at 45℃ 75%RH and dry heat treatment at 60°C to prolong drug release of tablets coated with chitosan acetate film containing magnesium stearate, talcum or titanium dioxide. From FT-IR, powder X-ray diffraction and DSC studies, stearate molecules liberated from magnesium stearate could react with protonated amino groups of chitosan and further was amide formation after moist heat treatment in chitosan film, thus incorporation of magnesium stearate was more effective than talcum and titaniym dioxide to prolong drug release. An addition of castor oil into film containing magnesium stearate increased the effectiveness to prolonging drug release. Urea at concentration of 5% could shorten the lag time and enhance the amount of drug release. The stability of this coated tablet was good and the drug release complied with the USP XXIII for 24 hours propranolol HCI extended release product. The mathematical expression, KGT2, was derived to describe the characteristic of drug release from soluble film coated preparation which the drug was in core material. This model expression could apply for the drug release from soluble chitosan film coated tablets and could predict the film dissolution time and rate and also the release rate of remained core tablet after film sissolution. KGT3 equation was sequentially developed from KGT1 by assuming that the film was altered to insoluble film by moist heat treatment. First order and KGT3 equations could be successfully fitted with most of sustained drug release profiles from tablets coated with modified chitosan acetate films after moist heat treatment. The release mechanism of encapsulated drug appeared concomitantly the diffusion controlled and osmoticlly driven force.