Chapter 1 work 1.

1 Aim of present work

Aim of present

In recent years, significant efforts have been devoted to develop oral sustained release formulations. The oral route of drug administration is still the most preferred despite recent innovations in other routes. For a drug with half-life of 20min to 8hr, dosage regimen can be fixed by giving the drug approximately every half-life or more frequently. For such drugs, patient compliance may be improved by fabricating the drugs in controlled release dosage forms. (Robinson J.R. et, al 1978; Charman S.A.et, al 2003; Venkatraman S. et, al 2000). The objectives of the present investigation are: 1. 2. 3. 4. To develop a suitable sustained release tablets of tizanidine hydrochloride (TIZH) using different polymers Evaluation of the prepared tablets for physical and chemical parameters. To develop suitable formula and procedure for the manufacturing of sustained release TIZH tablets in a relatively economical way. In vitro evaluation of tablets for the release characteristics. TIZH, the skeletal muscles relaxant acts as an anti-spastic agent. It is

available in the market as conventional tablets and as sustained release dosage forms. Few of pharmaceutical industry is manufacturing TIZH sustained release dosage forms. But, only one brand of TIZH is available as sustained release matrix form in market. (Atyabi F. et, al 1996). The bioavailability of the drug from a conventional dosage form is 40% due to the limitation of GI tract i.e. absorption is limited up to upper part of the GI tract.( Hilton AK. et, al 1992). So SR matrix tablets of TIZH can increase the bioavailability of the drug.( Costa P. et, al 2001, Bamba M. et, al 1979). In the present investigation, efforts were put to develop a sustained release TIZH tablet. Tizanidine hydrochloride (TIZH) The drug chosen for the present investigation was TIZH. It is effectively used in the treatment of management of spasticity, indicated in muscle pain as muscle relaxant. TIZH approximately 30% bounds to plasma proteins and is metabolized by the primary cytochrome P450 isoenzyme involved is CYP1A2, the metabolites of tizanidine are not known to be active. Its daily oral dose is 6-12 mg/day in divided doses. (www.drugbank.com)

Chapter 1 work

Aim of present

Rationale for drug selection: 1. 2. 3. Absorption of the TIZH is limited to upper part of the GI tract (stomach and upper part of small intestine) and bioavailability is 40%. TIZH has a biological half-life of 1 to 4.3 hours i.e., it requires three-times a day dosing. To maintain plasma concentration without the need of frequent dosing and reduce side effects unlike in case of conventional dosage form.

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Aim of present

1.2 References: Atyabi F., Sharma H L., Mohammad HAH. Fell JT. (1996). In vivo evaluation of novel gastric retentive formulation based on ion exchange resins. J Cont Rel; 42, 105-13. Bamba M., Puishenx F., Marty JP. Carstensen JT. (1979). Release mechanisms in gel forming sustained release preparations. Int J Pharm., 2,307-15. Charman S.A., Charman W.N. (2003). Modified-Release Drug Delivery Technology, 2nd edition, Marcel Dekker Inc, New York, 126. 1-19. Costa P., Lobo JMS. (2001) Modeling and comparison of dissolution profiles. Eur J Pharm Sci., 13,123-33. Hilton AK., Deasai P B. (1992) Invitro and In vivo evaluation of an oral sustained release dosage form of Amoxycillin trihydrate. Int J Pharm., 86, 79-88. Robinson J. R., Lee V. H. (1978) Controlled drug delivery, Marcel Dekker Inc., New York. 2,373-375. Venkatraman S., Darar N., Chester A., Kleiner L. (2000). Handbook of Pharmaceutical Controlled Release Technology, Marcel Dekker Inc. New York., 1,440-461. www.drugbank.com, 19/09/2008