Rajiv Gandhi University Of Health Sciences, Karnataka

Bangalore

Annexure – II

Proforma For Registration Of Subjects For Dissertation

1. Name of the candidate and address / CHOUDHARI ISHWAR HANUMANT
K.L.E.S’s COLLEGE OF PHARMACY
2nd BLOCK, RAJAJINAGAR,
P.B.NO. 1062,
BANGALORE-560 010
PERMANENT ADDRESS:
A/P SHIRALE
TAL. - BARSHI
DIST.-SOLAPUR- 414404
MAHARASHTRA
2. Name of the Institution / K.L.E.S’s COLLEGE OF PHARMACY,
2nd BLOCK, RAJAJINAGAR,
P.B.NO. 1062,
BANGALORE-560 010
3. Course of study and subject / MASTER OF PHARMACY- PHARMACEUTICAL TECHNOLOGY
4. Date of admission / 26-05-2008
5. Title of the Topic / “SCREENING OF TIZANIDINE HYDROCHLORIDE FOR TRANSDERMAL DELIVERY ".
6. Brief resume of the intended work:
6.1 Need For The Study:
Tizanidine[5-chloro-4-(2-imidazoline-2-ylamino)-2,1,3-benzothiodiazole hydrochloride] is a centrally acting α-2 adrenergic agonist indicated for the management of spasticity.1 The drug is orally administered and is available in the form of tablets and capsules ( Zanaflex tablets, 2 –8 mg). However, when orally administered, tizanidine undergoes extensive first pass metabolism and the estimated absolute bioavailability varies between 21- 40%.2, 3 Food has complex effects on tizanidine pharmacokinetics. Absorption differs with different formulations, which may result in increased adverse events or delayed/more rapid onset of activity depending upon the nature of the switch.2 Moreover, the drug is associated with some serious side effects. Tizanidine use occasionally causes liver injury.4 The pharmacodynamic effects of tizanidine hydrochloride, including not only its effects on spasticity but the incidence of somnolence and cognitive impairment, have been found to be significantly correlated with plasma tizanidine concentration.2 Because of short half life (2.5hrs), the drug needs frequent administration. Administration through a route that would bypass the hepatic metabolism and ensure the maintenance of plasma concentration just above the minimum effective level is likely to decrease the intensity of associated side effects and increase bioavailability.
Transdermal Drug delivery systems because of its rate limiting property by stratum corneum can offer steady plasma level over a prolonged period and also bypass the hepatic first pass metabolism.5 Hence there is a need to screen the drug for transdermal administration. This project is aimed at assessing the suitability of the drug for transdermal delivery.
6.2 Review Of Literature:
So far, no work has been done on tizanidine hydrochloride to assess its suitability for transdermal delivery. However, skin permeability studies have been carried out on different drugs with similar physicochemical/pharmacological class.
In vitro skin permeability of thiocolchicoside, a muscle relaxant, had already been investigated. The permeation experiments using iontophoresis had shown enhanced flux of thiocolchicoside compared with the passive control. The mechanism of enhanced transport was suggested to be electroosmosis.6
Another study evaluated the effect of enhancers, propylene glycol diperlagonate and propylene glycol, delivered as a mixture of innovative foam, on the flux of thiocolchicoside through excised human skin.Which increased the thiocolchicoside flux about three fold compared to control formulation.7
Eperisone hydrochloride, a muscle relaxant had been developed into a transdermal patch. The patch applied on rats showed better muscle relaxant activity compared to its oral counterpart.8
Iontophoresis was carried out on poorly water soluble drug glipizide. Steady state flux of 0.27 micromol/cm2/hr was reported which was thought to be sufficient to meet the demand of maintenance therapy.9
6.3 Objective Of The Study:
The aim of the present study is to screen tizanidine hydrochloride for the development of a transdermal dosage form.
To achieve this objective, the work will be divided under these headings:
1.  Evaluation the physicochemical parameters of the drug.
2.  Solubility studies in combination solvents (ethanol: water of various combinations) to select the donor vehicle of the drug.
3.  In-vitro passive permeability study through porcine ear skin using Franz diffusion cell.
4.  Evaluation of the effects of constant current (0.5mA/cm2) on the permeability of drug.
5.  If the permeation is found inadequate, permeation will be carried out using combination of enhancers and iontophoresis.
6.  Statistical analysis of the data.
7. Materials And Methods:
7.1 Source of data:
The reported data on pharmacokinetic and pharmacodynamic parameters will be collected from internet web, research papers, and journals. The experimental data will be generated in the laboratory of K.L.E.S’s college of pharmacy.
7.2 METHOD:
§  Study of research articles.
§  Laboratory investigation will include:
STUDY OF PHYSICO-CHEMICAL PROPERTIES:
Data on physicochemical properties (solubility, partition co-efficient, pKa etc.) will be generated using standard procedure and phase solubility study will be carried out.
PASSIVE PERMEATION STUDY:
This experiment will be carried out using Franz diffusion cell. The hydrated porcine skin sample will be sandwiched between the donor and receiver compartment with subcutaneous layer facing the donor compartment. The drug, in the form of solution, will be placed in the donor compartment and the receptor compartment will be filled with 0.9% NaCl or other suitable buffer. The sample will be withdrawn at predetermined intervals and will be assayed using spectrophotometer.
IONTOPHORETIC STUDY OF TIZANIDINE:
Iontophoresis can be defined as permeation of ionized drug molecules across biological membranes under the influence of electrical current. This study will be carried out by using iontophoretic apparatus associated with the constant current power supply (DC) using Ag/AgCl electrodes, the sample will be withdrawn at predetermined intervals and assayed using spectrophotometer.10
7.3 Does the study require any investigation or interventions to be conducted on patients or other humans or animals? If so please describe briefly.
NO.
7.4 Has Ethical Clearance Been Obtained From Your Institution In Case Of 7.3?
NOT APPLICABLE.
8. List of References:
1.  Stuart A, Dunbar MB. Alpha 2 adrenoreceptor agonist in the management of chronic pain. Best Practice & Research Clinical Anesthesiology 2000; 14: 471-481.
2.  Herbert RH, Jaymin S. Relative bioavailability of Tizanidine 4 mg capsule and tablet formulations after a standardized high fat meal: A single-dose, randomized and open-label crossover study in healthy subjects. Clinical Therapeutics 2007; 29: 661-669.
3.  http://www.rxlist.com/zanaflex-drug.htm.
4.  http://en.wikipedia.org/wiki/tizanidine.
5.  Jurgen D, Remy M and Ulla T, et al. Pharmacokinetics and pharmacodynamics of a new transdermal delivery system for Bopindolol. Journal of Clinical Pharmacology 1991; 31: 671-676.
6.  Artusi M, Nicoli S, Colombo P, et al. Effect of chemical enhancers and iontophoresis on Thiocolchicoside permeation across rabbit and human skin in vitro. Journal of Pharmaceutical Sciences 2004; 93: 93–103.
7.  Bonina F, Puglia C, Trombetta D, et al. Vehicle effects on in vitro skin permeation of Thiocolchicoside. Pharmazie 2002; 57: 750-752.
8.  Yang SI, Park HY, Lee SH, et al. Transdermal Eperisone elicits more potent and longer-lasting muscle relaxation than oral Eperisone. Pharmacology 2004; 71(3):150-156.
9.  Jain A, Ghosh B,Rajghor N, Desai BG. Passive and ionophoretic permeation of Glipizide. European Journal of Pharmaceutics and Biopharmaceutics 2008: 69: 954-63.
10.  Wang Y, Thakur R, Fan Q, Michniak B. Transdermal iontophoresis: combination strategies to improve transdermal iontophoretic drug delivery. European Journal Pharmaceutics and Biopharmaceutics 2005; 60: 179-191.
9. / Signature of the candidate
10. / Remarks of the guide / Recommended
11. / 11.1 Name and Designation of the guide / Dr. Bijaya Ghosh
Dept. of Pharmaceutical Technology, K.L.E.S’s College of Pharmacy, Rajajinagar, Bangalore-560010.
11.2 Signature
11.3 Head of the Department / Dr. Bijaya Ghosh
Head of the Department
Dept. of Pharmaceutical Technology, K.L.E.S’s College of Pharmacy, Rajajinagar, Bangalore-560010
11.4 Signature
12 / 12.1 Remarks of the Chairman and Principal / Recommended for registration
12.2 Principal / Dr. Purnima Ashok
Principal
K.L.E.S’s College of Pharmacy,
2nd block, Rajajinagar,
Bangalore-560010
12.3 Signature