Study on multilayer ethylcellulose matrices for controlled release of benzoic acid

Reena Singhal, A Nagpal, G Mathurb
2001 Indian Journal of Chemical Technology   unpublished
Matri x dev ices based on ethyl cellu lose (EC) for controlled release (CR) applicati ons were investigated for zero order release. These matrices were prepared by solvent casting and contained three or five layers arranged in symmetri cal fashion with benzoic ac id (BA) l o:.~d ed on ly in inner layers; while the outermost layers were kept free from BA. It wJs foun d that three layer matrices maintain high release rates inspite of outer barrier layer and heavy initi al release (burst effect)
more » ... se (burst effect) was sig-nifi cantl y n:duced: but linear release pro fil e was not obtained. In five layer matrices four type of drug distribution profi les were tested and it was found that desce nding staircase type concentr::ui on gradien t gave linear release profil e. with enh anced release duration and reduced burst effect. Controlled release (CR) technology is an emerging area of research which deals with slow/controlled release of compounds like pharmaceuticals, harmones, pesticides, herbicides, molluscicles etc., in body or environment'. Products based on CR offer advantages like prolonged action with ease of administration, drastic reduction in side-effects, prevention of degradation of drug etc. The concept of CR is particularly very useful in pharmaceuticals as here the fiuctuations in drug concentration in blood are minimum and it is controlled below toxic level, leadi ng to lesser side-effects as well as better patient compliance. The CR devices are based on various mechanisms responsible for release such as diffusio n, osmotic pressure, biological or chemical reaction etc. 2 Matrix type CR devices are probably the simplest and least expensive way to control the release of drug matrix devices applications. Here the active agent is dispersed or dissolved in an inert polymer and drug is released by diffusion process. Here the release rate decreases with time and polymer matrices exhibit first order release (i.e. rate oc. . Jt) which shoulcl 2 be zero order/constant ideally. The reason for fall in release rate includes increasing diffusional distances with time and high initi al release also known as "burst effect". Various CR systems utilizing matrix type devices are being effectively used in clinical areas like contraceptives (Norplant H), immunization, tumour • For correspondence (Fax: +9 1-5 12-545312) (T A F), transdermal patches, glucoma and other common ailments. In addition CR technology has potential application in veterinary applications like delivery of growth regulators, antiparasitic drugs, nutrients, ilea/tick collors etc. Several approaches were tried for getting linear release rates from diffusion controlled polymeric matrices, earl ier approach was alterations in the matrix geometry so that increasing diffusional distance was compensated by an increasing surface area and linear release was obtained. Such matrix geometry include a sectioned cylinder.3, hemisphere 4 etc., but they cou ldn't be commercialized clue to lack of suitable production techniques for such shapes on large-scale. Another possible approach is to provide increasing drug concentration in the matrix with increasing diffusional distance. Matrix devices based on various polymers containing coating on both outer surfaces have shown lesser burst effect and improved release profile, but completely linear release rates were not obtained. Matrix devices for oral appl ication in film 5 · 6 and tablet 7 form, containing non-uniform/gradient drug distribution were found to be effective for 8-12 h, but such stud ies have not been extended to larger time durations based release systems. In the present investigations an attempt has been made to achieve linear release profiles by preparing matrices with heterogeneous drug distribution consisting of three and five layers. These matrices were prepared from ethyl cellulose (EC) as it is non-toxic, has good film forming properties even at high