The drug release in the colonic region from different CDDS is evaluated by different methods of in vitro and in vivo release studies, which show the success rate of different designs of colon drug delivery systems. Depending upon the method of preparation different evaluation methods are proposed. A successful colon specific drug delivery system is one of that remains intact in the physiological environment of stomach and small intestine, but releases the drug in the colon.
In-vitroEvaluation:
Different in vitro methods are used to evaluate the colonic drug delivery systems. In in-vitro studies the ability of the coats/carriers to remain intact in the physiological environment of the stomach &
small intestine is assessed by drug release studies in 0.1N HCl for two hours (mean gastric emptying time) and in pH 7.4 phosphate buffer for three hours (mean small intestine transit time) using USP dissolution apparatus. In case of micro flora activated system dosage form, the release rate of drug is tested in vitro by incubating in a buffer medium in the presence of either enzymes (e.g.
pectinase, dextranase) or rat/guinea pig / rabbit
80 caecal contents. The amount of drug released at different time intervals during the incubation is estimated to find out the degradation of the carrier.
In-vivoEvaluation:
Like other controlled release delivery systems, the successful development of the CDDS is ultimately determined by its ability to achieve release in colonic region thus exerts the intended therapeutic effect. When the system design is concerned &
prototype formulation with acceptable in vitro characteristics is obtained, in vivo studies are usually conducted to evaluate the site specificity of drug release and to obtain relevant pharmacokinetic information of the delivery system. Although animal models have obvious advantages in assessing colon specific drug delivery systems, human subjects are increasingly utilized for evaluation of this type of delivery systems. The preferable animals to evaluate CDDS are rats, guinea pigs and dogs.
Animal models:
Different animal model are used for evaluating in vivo performance of colon specific drug delivery system. Guinea pigs were used to evaluate colon specific drug delivery from a glucoside prodrug of dexamethasone. Other animal model used for the in vivo evaluation of colon specific drug delivery system includes the rat and the pig.Technique for monitoring in vivo behavior of the colon specific drug delivery system in humans: A variety of technique like
String technique
Endoscopy
Radiotelemetry
Roentgenography and
Gamma scintigraphy.
Were used for monitoring the in vivo behavior of a oral dosage forms. points, the tablet was withdrawn from the stomach by pulling out the string and physically examining the tablet for the sing of disintegration. In some studies, the tablets were recovered by inducing a
vomiting reflex. The presence of foreign object, such as string in GI tract may alter its motility and physicochemical environment. The psychological stress and anxiety associated with this method also affect the motility of GI tract. (S.P.vyas n.d.) Endoscope technique:
This technique has been employed by Hey et al, (1979). It is an optical technique in which a fibre scope (gastroscope) is used to directly monitor behavior of dosage form after ingestion. This method required administration of a mild sedative to facilitate the swallowing of endoscopic tube. The sedative its self may alter gastric emptying and GI motility. The psychological factor also contributes to the change in motility of the GI tract. (H.Hey environment to non external antenna attached to the body of subject, so it is necessary to physically attach the dosage form to the capsule which in turn may affect the behavior of dosage form being prevents the evaluation of commercially available product which does not contain buffer salts.
(B.kinter 2003), (H.M.Brash 1976) Roentgenography:
The inclusion of radio opaque material in to a solid dosage form enables it to be visualized by use of X-rays. By incorporating barium sulphate in to pharmaceutical dosage form, it is possible to follow the movement, location and integrity of dosage form after oral administration by placing the subject under a fluoroscope and taking the series of X-ray at various points. This method was first used by Losinsky & Diver (1933) and has been used by many subsequent workers. This technique use by Dew et al (1982) to evaluate the capsule dosage form coat with Eudragit to deliver a orally ingested drug to the colon using barium sulphate as radio opaque material the use of X-rays involves the exposing the subject to fairly high radiation dose as
81 several photograph must be taken. Information can not be obtained on continuous basis. The radio opaque material, such as barium sulphate has high density and may not be good model. (W.H.Browers n.d.)
Gamma scintigraphy:
The most useful technique, to date, to evaluate the in vivo behaviour of dosage form in animals &
humans is external scintigraphy or gamma scintigraphy. Work in this area began in 1970 through the modification of standard nuclear medicine method, to monitor the in vivo behaviour of dosage forms. Gamma scintigraphy requires the presence of gamma emitting radioactive isotopes in the dosage forms that can be detected in vivo by an external gamma camera. The dosage forms can be radiolabelled using conventional labeling or neutron activation methods.
Of all these methods available, gamma scintigraphy is the most widely used noninvasive technique for studying the in vivo behaviour of oral dosage form under the normal physiological condition. (H.M.Brash 1976) (Hebden J.M 1999) (Adkin D.A 1997)
Advantages:
Gives a very little radiation exposure to the participating subject compared to Roentgenography (X-Ray)
a) Gives both qualitative & quantitative results, which is not possible with other techniques b) Totally noninvasive method &
c) Allows for the in vivo evaluation of dosage forms under normal physiological conditions.
A brief account of gamma scintigraphy including methodology & applications is given below.
Disadvantages:
Inability to accurately quantify the activity in the small bowel because of its coiled nature, b) it is not possible to label all compounds /Drug of interest’s) the gamma scintigraphy assembly is expensive d) require qualified personnel for operation.
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