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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE,
KARNATAKA.
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. Name of the candidate and address
(in block letters)SUNIL LAKSHAMAN RAYKAR
BAPUJI PHARMACY COLLEGE
S.S. LAYOUT, SHAMANUR ROAD
DAVANGERE – 577 004
2. Name of the institution BAPUJI PHARMACY COLLEGE
3. Course of study and subjectM. PHARMACY
(INDUSTRIAL PHARMACY)
4. Date of admission to course 29-12-2012
5. Title of the topicFABRICATION AND IN VITRO
EVALUATION OF MINOXIDIL
MATRIX TABLETS
6. BRIEF RESUME OF THE INTENDED WORK
6.1 Need for the study
The word new or novel with respect to drug delivery system is a search for
something out of necessity. An appropriately designed sustained or controlled release
drug delivery system can be major advance towards solving the problem associated with
the existing drug delivery systems.1
The oral route is the most common route of drug administration because of its
advantages in terms of convenient administration, thus leading to increased patient
compliance. Extended release formulations in many cases provide further significant
advantages, including improved therapeutic effect, increased patient compliance by
reducing dosing frequency and decrease in incidence and or intensity of adverse effect
by constant plasma drug concentration.2
Conventional immediate release tablet has to be administered, three to four times in a
day. most of the patients to maintain the therapeutic plasma drug concentration
throughout the dosing intervals 3. This increased complications and expense involved in
marketing of new drug entities has focused greater attention on development of
sustained release (SR) or controlled release (CR) drug delivery systems. Sustained or
controlled release delivery systems can achieve predictable and reproducible release
rates, extended duration of activity, decreased toxicity, reduction of required dose,
optimized therapy limiting fluctuation within the therapeutic range, decreasing dosage
frequency and better patient compliance. Matrix type sustained delivery systems are
popular because of their ease of manufacturing.4-5
The simplest way to retard drug release is to disperse it in a solid matrix. The matrix
system is commonly used for manufacturing sustained release dosage forms especially
tablets because it makes such manufacturing easy.6
Minoxidil is an orally effective vasodilator with antihypertensive activity, which
is more potent than hydralazine. More than 95% of the drug is absorbed from the
gastrointestinal tract and a plasma elimination half-life is 4.2 hr. Administration of
minoxidil in a sustained release dosage would be more desirable for antihypertensive
effects by maintaining the therapeutic plasma drug concentrations. To reduce the
frequency of administration and to improve patient compliance, a once-daily sustained-
release formulation of minoxidil is desirable.
Previously, studies have been carried out to formulate various sustained release drug
delivery devices, including Gel7, Transdermal patches,8 Niosomes, cream or ointment9
sustained release drug delivery offers safe and ease method of drug utilization, because
can be promptly terminated in case of toxicity by removing other dosage form from
sustained release.
Minoxidil is a potent direct vasodilator, which reduces both systolic and diastolic
blood pressure by lowering peripheral resistance. The drug acts predominantly on the
arterioles and has little effect on the venous capacitance vessels. In patients with benign
hypertension not responding well to traditional therapy, better control of blood pressure
with minoxidil may prevent the deterioration of renal function which occurs in the
majority of such patients.
6.2 Review of the study
Literature review for undertaking the study was done by referring to articles published in
various National and International Journals, official standard books and referring to
various websites on the internet. Review of literature indicates that enormous work has
been reported on matrix tablets. More relevant works are explained systematically as
follows
. Khan Arshadbashir, et al., Formulattion and Evaluation of sustained release matrix
tablets of Propranolol Hydrochloride using Sodium Carboxy Methyl Guar (SCMG) as
rate sustaining polymer. SCMG is a guar gum derivative, which was investigated as a
sustaining material to formulate sustained release tablets of the model drug, Propranolol
Hydrochloride. 10
Prajapatib G et.al. Prepared and Evaluated in vitro formulations of once-daily
sustained-release matrix tablets of Losartan Potassium. Objective of the present study
was to develop Hydrophilic polymer and Hydrophobic polymer based matrix Losartan
Potassium sustained release tablet which can release the drug up to time of 24 hr in
predetermined rate. It is readily absorbed from the gastrointestinal tractwith oral
bioavailability of about 33% and a plasma elimination half-life ranging from 1.5 to 2.5
hr. Administration of LP in a sustained release dosage would be more desirable for
antihypertensive effects by maintaining the plasma concentrations of the drug well
above the therapeutic concentration. From in vitro dissolution profile, Batch B4 was
prepared with blend of HPMC K4M (67.2 mg), HPMC K200M(90mg) and Eudragit
RSPO(112.5 mg), where drug release was about 94-98%. Batch B4 showed highest
similarity factor values (f2 = 67.76). 11
Dhirendrakumar, et al. Designed and evaluated sustained-release matrix once-
daily formulation of Stavudine, to increase therapeutic efficacy, reduce frequency of
administration and improve patient compliance. The sustained release tablets were
prepared by Direct Compression and formulated using different drug: polymer ratios,
formulations such as F1to F15. Hydrophilic polymers like Hydroxy Propyl Methyl
Cellulose (HPMC), Carboxymethyl Cellulose (CMC) and Starch 1500 were used. SEM
studies of the formulations were carried out for the confirmation of mechanism of drug
release. The in vitro drug release characteristics were studied in both simulated gastric
and intestinal fluids for a period of 24 hr using USP Type 2 dissolution apparatus.
Mathematical analysis of the release kinetics indicated a coupling of diffusion and
erosion mechanisms. The study proves that the developed sustained release tablet is
capable of releasing the drug in a sustained manner for 24 hr.12
Jaberemami, et al. Prepared and evaluated in-vitro of sustained-release matrix
tablets of Flutamide using Synthetic and Naturally occurring polymers. The sustained-
release matrix tablets of Flutamide were prepared by direct compression method using
different polymers. Cellulose ethers (HPMC and NaCMC), Natural gums (Guar and
Xanthan gums) and compressible Eudragits (RSPO and RLPO) and their combinations
were used in different ratios to examine their influence on tablet properties and drug
release profile Frequent dosing of the potent anti-androgen, flutamide, is necessary to
reach a therapeutic level for the treatment of prostatic carcinoma. Sustained delivery of
the drug could reduce the adverse effects such as gastrointestinal disorders and improve
patient compliance.13
Anton Smith, et al. Developed and Evaluated of Ondansetron Hydrochloride
sustained release matrix tablets. The objective of the present study was to develop
sustained release matrix tablets of Ondansetron Hydrochloride [5mg] formulated
employing Hydroxy Propyl Methyl Cellulose polymer and the sustained release
behaviour of the tablets was investigated. Tablets were prepared by Wet Granulation
methodsThe granules were evaluated for angle of repose, bulk density and drug
content .The tablets were subjected to thickness, diameter, weight variation test,
hardness, friability, drug content and in vitro release studies. Formulation was optimized
on
the basis of acceptable tablet properties and in vitro drug release. The results of
dissolution studies indicated that formulation FV (drug to polymer ratio 1:3) the most
successful of the study, exhibited drug release pattern very close to theoretical release
profile. All the formulations (except FV) exhibited diffusion – dominated drug
release.The mechanism of drug release from FV was diffusion coupled with erosion.14
V N. Deshmukh, et al.,15 Designed and evaluated sustained release Metoprolol
Succinate tablet using Hydrophilic gums As release modifiers. The objective of this
study was to design and evaluate oral sustained drug delivery system for Metoprolol
Succinate using Natural hydrophilic gums such as Karaya gum and Xanthan gum as a
release modifier. Matrix tablets were prepared by wet granulation method and were
evaluated physical & chemical parameters, and Stereo Photography. No chemical
interaction between drug and gums was seen as confirmed by IR studies. The matrix
formulation F8showed sustained release of Metotprolol succinate by the diffusion
mechanism.
Saleha. Alsuwayeh, et al. Carried out in-vitro and in-vivo Evaluation of sustained
release Hydralazine Hydrochloride tablets prepared by Thermal Granulation Technique,
the aim of this work was to use the Thermal Granulation Technique to formulate
Hydralazine Hydrochloride (HLZ) as sustained release tablets using Hydroxyl Propyl
methyl Cellulose (HPMC) and Poly Ethylene Glycol 6000 (PEG 6000) blend as
hydrophilic heterogeneous matrices.16
K. Raghuram Reddy, et al. Developed once-daily sustained-release matrix tablets
of Nicorandil: formulation and In vitro evaluation. The objective of the present study
was to develop once-daily sustained-release matrix tablets of Nicorandil, a Novel
Potassium channel opener used in cardiovascular diseases. The tablets were prepared by
the wet granulation method. The results of dissolution studies indicated that formulation
F-I (drug-to-HPMC, 1 4; ethanol as granulating agent) could extend the drug release up
to 24 hours. In the further formulation development process, F-IX (drug-to-HPMC, 1 4;
EC 4% wt/vol as granulating agent), the most successful formulation of the study,
exhibited satisfactory drug release in the initial hours, and the total release pattern was
very close to the theoretical release profile. All the formulations (except F-IX) exhibited
diffusion-dominated drug release. The mechanism of drug release from F-IX was
diffusion coupled with erosion.17
P. Khemariya, et al. Developed and carried out studies evaluation of sustained-
release matrix tablets of Diltiazem. The purpose of the present research work was
develop once-daily sustained-release matrix tablet containing water-soluble drug
(Diltiazem) that is a Novel Calcium channel blocker used in cardiovascular diseases.18
. P R. Radhikaa, et al. Formulated and evaluated sustained release matrix tablets of
Glipizide. The purpose of this study was to develop a new monolithic matrix tablet to
completely deliver Glipizide in a zero order manner over a sustained period. The
granules were prepared by wet granulation method and thereby formulated as F-1, F-2.
F-3 and F-4 by using the above bring up polymers with other ingredients. The granules
of different formulations were evaluated for angle of repose, loose bulk density and
tapped density, compressibility index, total porosity, and drug content.19
Dr. Umesh. D. Shivhare, et al. Formulated and evaluated sustained release tablets
of Aceclofenac. The objective of the present study was to develop “once daily” sustained
release tablets of Aceclofenac by Wet Granulation using Carboxy Poly Methylene
polymer. The physicochemical properties of tablets were found within the limits.
Formulation F2 & F9containing Carbopol 971P and Carbopol 974P were found to
release the drug in sustained manner up to 24 hr and were stable under accelerated
conditions of temperature for 6 months since there were no significant changes in drug
content and physical parameters.20
R. Nagaraju, et al. Formulated and Evaluated bilayer sustained release tablets of
Salbutamol and Theophylline. They are available in conventional dosage forms,
administered four times a day, leading to saw tooth kinetics and resulting in ineffective
therapy. The combination of these two drugs in a single dosage form will enhance the
patient compliance and prolong broncho dilation pients are Povidone Micro Crystalline
Cellulose in different ratios. 21
6.3 Objectives of the study
The objectives of the present research study are:
Pre-formulation studies includes,
Determination of melting of minoxidil, Drug- excipients compatability study,
Interference of polymer in uv determination of drug compressibility index, etc
Development of suitable analytical method.
Screening of excipients for suitability.
Formulation of Minoxidil sustained release matrix tablets with different polymer
7.
composition.
Evaluation of the physico-chemical characteristics of the prepared sustained
release matrix tablets.
To determine in vitro of drug release from the matrix tablets
To evaluate the drug release kinetics and mechanism for the prepared
formulations.
To assess the stability of the prepared formulations.
Evaluation of pre compression and post compression parameters for formulated
dosage forms.
MATERIALS AND METHODS
7.1 Source of data
The physicochemical properties of drug and polymers will be collected from the
national and International journals, internet facilities, related articles, and standard books
from library of the college.
7.2 Methods of collection of data
(Including sampling procedure, if any)
a. Analytical method for the estimation of Minoxidil will be developed in
phosphate buffer of PH 7.4
b. Evaluation of physical properties of powder blend of tablet batches such as,
angle of repose, bulk density, compressibility index, etc.
c. Formulation of sustained release matrix tablets of the minoxidil using different
polymers.
d. The sustained release matrix tablets were evaluated for in process and finished
product quality control tests such as, appearance, dimensions (diameter and
thickness), uniformity of weight, hardness, friability, content uniformity, etc.
e. In vitro evaluation of prepared sustained release matrix tablets of minoxidil for
the drug release characteristics.
7.3 Does the study require any investigations or interventions to be conducted
on patients or other humans or animals? If so, please describe briefly.
Not required.
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
Not applicable.
8 LIST OF REFERENCES
1. Najmuddin M, Vishal P, Aejazahmed,Shelar S, Khan T. Preparation and
Evaluation of Flurbiprofen Microcapsules for Colonic Drug Delivery System,
Int J Pharmacy and Pharmaceu Sci, 2010;2(2):83-7.
2. Dhirendra k, Vivek D, Shaila L, Brajesh P, Kavita R. Gajbhiye, Sarvesh P,
Design and Evaluation of Sustained-Release Matrix Once-daily Formulation of
Stavudine, Int J of Drug Del, 2010;2:125-34.
3. Saleha, Mohammed H. El-Shaboury, Saeed M. Al-Baraki, Abubakar S. Elg,et,.al
In-vitro and in-vivo Evaluation of Sustained Release Hydralazine Hydrochloride
Tablets prepared by Thermal Granulation Technique. Australian j of Basic and
Applied Sci, 2009;3(3):2866-75.
4. Radhikaa PR, Pala TK, Sivakumar B.Formulation and Evaluation of Sustained
Release Matrix Tablets of Glipizide. Iranian J of Pharmaceut Sci Autumn, 2009;
5(4):205-14.
5. Subal C. Basa k, Karthikeyan J, Bharati B. In-vitro evaluation and Release Rate
Kinetics of Matrix Type Sustained Release Tablet containing Aceclofenac.The
Internet J of Pharmacol, 2010;8(2):6
6. Deshmukh VN, Singh SP, Sakarkar DM. Formulation and Evaluation of
Sustained Release Metoprolol Succinate Tablet using Hydrophilic Gums as
Release Modifiers, Inter J of Pharm-Tech Research, 2009;1(2):159-163.
7. Sunil G, Sadhana S, Imran T, Nityanand Z, Shekhar T, Uttara S. Gov. Coll of
Pharmacy, Aurangabad, MH, India. Int J Pharmacy Research and Allied Sci
(2012),1(1) 41-47.
8. Venna D, Thakur RS, Arshad Bk. Krupanidhi Coll of Pharmacy, Asian J of
Pharma and Life Sci , 2013;3(1):22-31
9. Chia-Ming C, Flynn GC, Weiner ND , Addicks WJ, Szpunar GJ. University
of Michigan. Int J Pharmaceu, 1989;(49):109-14
10. Khanarshad B, Nanjundaswamy NG. Formulation and Evaluation of Sustained
Release Matrix tablets of Propranolol Hydrochloride using Sodium Carboxy
Methyl Guar as rate sustaining polymer, Arch Pharm Sci& Res, 2009;1(2):203 -
06.
11. Prajapatib G, Patel KR. Formulation and in-vitro evaluation Once-daily
Sustained-Release Matrix Tablets of Losartan Potassium, Int J of Medical and
Clinical Research, 2010;1(1);01-7.
12. Dhirendra K, Vivek D, Shaila L, Brajesh P, Kavita R. Gajbhiye, Arvesh P.
Design and Evaluation of Sustained-Release Matrix Once-Daily formulation of
Stavudine, Int J of Drug Del, 2010;2:125-34.
13. Emami J, Tajeeddin M, Ahmadi F. Preparation and In-vitro Evaluation of
Sustained-Release Matrix Tablets of Flutamide using Synthetic and naturally
occurring polymers, Iranian J of Pharmaceu Research, 2008;7(4):247-57.
14. Anton S, Kottaimuthu A, Waghbhushan P, Manavalan R, Formulation
Development and Evaluation of Ondansetron Hydrochloride Sustained Release
Matrix Tablets. J Pharmaceu. Sci & Research, 2009;1(4):48-54
15. Deshmukh VN, Singh SP, Sakarkar DM. Formulation and evaluation of
sustained release metoprolol Succinate tablet using hydrophilic gums as Release
Modifiers, Int J of Pharm tech Research, 2009;1(2):159-63.
16. Saleha. mohammed H. El-shaboury, Saeed M. Al-Baraki, Abubakar et,.al In-
vitro and In-vivo Evaluation of Sustained Release Hydralazine Hydrochloride
Tablets prepared by Thermal Granulation Technique, Australian J of Basic and
Applied Sci, 2009;3(3):2866-75
17. Raghuramreddy K, Srinivas M, Srinivas R. Formulation & in vitro evaluation
Once-daily Sustained-Release Matrix Tablets of Nicorandil, AAPS pharma sci
tech, 2003;4(4):1-9.
18. Khemariya P, Jain AK, Bhargava M, Singhai SK, Goswami S, Goswami R.
Preparation and In-vitro Evaluation of Sustained-Release Matrix Tablets of
Diltiazem. Int J of Advances in Pharmaceu Sci, 2010;1:267-3.
19. Radhika PR, Pala TK, Sivakumar T. Formulation and Evaluation of Sustained
Release Matrix tablets of Glipizide. Iranian J of Pharmaceu Sci Autumn, 2009;
5(4):205-14.
20. Dr.Umesh D, Shivhare, Nandkishord A, Dr. Kishore PB, Dr. Vijay BM,
Digvijay UA, Formulation Development, Evaluation and Validation of Sustained
Release Tablets of Aceclofenac, Int J of Pharmacy and Pharmaceu Sci, 2009;
1(2):74-80.
21. Nagaraju R, Rajeshkaza. Formulation and Evaluation of Bilayer Sustained
Release Tablets of Salbutamol and Theophylline, Int J of Pharmaceu Sci and
Nanotechnology, 2009;2(3):638-46
9. Signature of the Candidate
10. Remarks of the Guide:
11. Name and Designation of (In block letters)11.1 Guide
11.2 Signature
11.3 Co guide (If any)
11.4 Signature
11.5 Head of the Department
11.6 Signature
Mr. MANJUNATHA K M. M. Pharm
senior lecturerDepartment of Industrial PharmacyBapuji Pharmacy College, Davangere.
Dr. J. THIMMASETTY M. Pharm, ph. D
Head of the Department of Industrial Pharmacy
Bapuji Pharmacy College, Davangere.
12. 12.1 Remarks of the Principal
12.2 Signature