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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA
BANGALORE
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
MAHESH R KALYANPUR.
K.L.E.S’s COLLEGE OF PHARMACY
2nd BLOCK, RAJAJINAGAR,
P.B.NO. 1062,
BANGALORE-560 010
1. Name of the candidate and address
PERMANENT ADDRESS:
NEAR GUN GUNI SCHOOL.
ROYAL STREET, HONAVAR.
KARWAR DIST.
KARNATAKA – 581 334.
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 PHARMACYPHARMACEUTICAL TECHNOLOGY
4. Date of admission
13-06-2008.
5. Title of the Topic
"DESIGN AND CHARECTERIZATION OF
RITODRINE HYDROCHLORIDE
TRANSDERMAL
DELIVERY BY PASSIVE DIFFUSION AND
IONTOPHORESIS."
6. BRIEF RESUME OF THE INTENDED WORK:
6.1 NEED FOR THE STUDY:
Transdermal Drug delivery systems (TDDS) by virtue of its rate limiting property of stratum
corneum offer many benefits over conventional drug therapy. It can decrease fluctuation in plasma
drug concentrations and increase bioavailability by bypassing the hepatic first pass metabolism.
Lower incidence of adverse effects and higher patient compliance is also expected from TDDS.1
Ritodrine, a selective β-2 adrenergic agonist (sympathomimetic), is used as tocolytic agent in the
treatment of premature labor. Treatment is normally done by IV loading followed by repeated
administrations of oral dose for a prolonged period of time (Up to 35 weeks).2 As the drug has got
short half life it needs to be administered every 2 hrs. High oral dose of ritodrine is avoided
because of its potential to cause significant side effects and post-natal complications. Maintenance
of the plasma concentration at a fixed (effective) level is desirable for the therapy. As transdermal
drug delivery can offer the advantages of intravenous infusion, 2 the drug appears to be a good
candidate for transdermal drug delivery systems (TDDS). So far no work has been done on
ritodrine hydrochloride to assess its suitability for transdermal drug delivery. The present study
aims to bridge that gap. Ritodrine is available as the hydrochloride salt and is extremely watersoluble. As stratum corneum offers high resistance to the permeation of hydrophilic moieties
iontophoresis seems to be a better option for transdermal administration of ritodrine hydrochloride.
6.2 REVIEW OF LITERATURE:
So far no work has been done on ritodrine hydrochloride to assess its suitability for transdermal drug
delivery. However, Iontophoresis has been carried out on different drugs with similar
physicochemical properties.3-4
Buspirone hydrochloride was studied for iontophoretic delivery.5 Iontophoresis at 0.5 mA/cm2,
could achieve a steady state flux of buspirone hydrochloride (350 µg/cm2/h), which was thought to
be therapeutically effective if clinically duplicated. Importantly, 24 h of iontophoresis at 0.5
mA/cm2 did not affect skin morphology and after the current was switched off, the skin’s
permeability to buspirone hydrochloride rapidly reverted to its pre-iontophoretic level.
The effect of the stratum corneum on skin permeability of triprolidine hydrochloride was evaluated
by studying the skin permeation through a stripped mouse skin using a side-by-side diffusion cell.6
The permeation rate of triprolidine hydrochloride in the stripped skin was greatly larger than that in
the whole skin. Thus it showed that the stratum corneum acts as a barrier of skin permeation.
Novel combination strategies, where iontophoresis was used with other devices have been reported
to enable successful transdermal drug delivery systems7
6.3 OBJECTIVE OF THE STUDY:
The aim of the present study is to screen ritodrine hydrochloride transdermal delivery by passive
diffusion and iontophoresis.
To achieve this objective the work will be divided under these headings:
1. Evaluation the physicochemical parameters of the drug for the Transdermal drug delivery
systems.
2. Evaluation the solubility of in the donor and receptor fluids.
3. Evaluation of the in-vitro passive permeability studies of the drug through porcine ear skin
using Franz diffusion cell.
4. Evaluation of the effects of constant current of 0.5mA/cm2 on the permeability of drug for
iontophoretic delivery.
5. Evaluation of the permeation effects the drug under interrupted current
6. If the permeation is found to be inadequate a permeation studies will be carried out using a
combination of enhancers and iontophoresis.
7. Statistical analysis of the data.
7. MATERIALS AND METHODS:
7.1 SOURCE OF DATA:
The reported data on Pharmacokinetic and Pharmacodynamic parameter will be collected
from internet web, research papers, 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 that includes:
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 RITODRINE:
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. Similarly for interrupted current study. The current will
be applied to initial hours and passive permeation will be allowed for the rest of the
period.8
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. 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.
2. Holleboom CAG, Merkus JMWM and Van ELWM. A loading-dose infusion scheme for
intravenous tocolysis with Ritodrine: a pilot study. European Journal of Obstetrics &
Gynecology and Reproductive Biology 1987; 26 (2):119-126.
3. Singh G, Ghosh B, Dave K and Somashekar V. Transdermal delivery of Vanlafaxine
hydrochloride: passive diffusion and iontophoresis. AAPS Pharm Sci Tech DOI 2008;
1208/s 12249-008:911-3.
4. Anroop B, Ghosh B, Parcha V, Khanam J. Comparative Skin permeability of Metoprolol
tartrate and its ester prodrugs by passive permeation and iontophoresis. Asian Journal of
Pharmaceutical Sciences 2008; 3:1-11.
5. Victor M, Mohammad MAK, Michniak BB. Enhanced iontophoretic delivery of Buspirone
hydrochloride across human skin using chemical enhancers. International Journal of
Pharmaceutics 2003; 264: 73–83.
6. Sang-Chul Shin, Lee Hyun-Jin. Enhanced transdermal delivery of Triprolidine
hydrochloride from the ethylene-vinyl acetate matrix. European Journal of Pharmaceutics
and Biopharmaceutics 2002; 54: 325–328.
7. Wang Y, Thakur R, Fan Q, Michniak BB. Transdermal iontophoresis: Combination
strategies to improve transdermal iontophoretic drug delivery. European Journal of
Pharmaceutics and Biopharmaceutics 2005; 60920: 179-91.
8. Langer R. Transdermal drug delivery: past progress, current status, and future prospects.
Advances in Drug Delivery Review 2004;56:557-58.
9.
Signature of the candidate
10.
Remarks of the guide
11.1 Name and Designation of the
guide
Recommended
Dr. Bijaya Ghosh
Dept. of Pharmaceutical Technology,
K.L.E.S’s College of Pharmacy,
Rajajinagar, Bangalore-560010.
11.2 Signature
11.
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
12.1 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
12.3 Signature