Formulation and in Vitro Evaluation of Matrix Tablets Containing Pioglitazone

FORMULATION AND IN VITRO EVALUATION OF MATRIX TABLETS CONTAINING PIOGLITAZONE

Synopsis for M.Pharm dissertation

Submitted to

Rajiv Gandhi University of Health Sciences, Bangalore,

Karnataka

Mr. BHAIRAPPA S SHEDYAL

B.Pharma

Under The Guidance Of

Dr.C.C.PatilM.Pharma, PhD

Professor & HOD

Dept. of Pharmaceutics

BLDEA’s College of Pharmacy,

BLDE University campus, Bijapur-586 103

2013-2014

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1 /

Name of the candidate and address

/ BHAIRAPPA SHEDYAL,

BLDEA’S COLLEGE OF PHARMACY

UNIVERSITY CAMPUS, BIJAPUR-586 103

PERMANENT ADDRESS
BHAIRAPPA SHEDYAL
s/o SIDDAPPA SHEDYAL
BADDUR LANE ,BANAHATTI-587311 Tq: JAMAKHANDI
Dist: BAGALKOT email:
2 / Name of the institution /

BLDEA’S COLLEGE OF PHARMACY

UNIVERSITY CAMPUS, BIJAPUR-586 103

3 /

Course of study and subject

MASTER OF PHARMACY IN PHARMACEUTICS

4 /

Date of the admission

/ 02-08-2012
5 /

Title of the topic: FORMULATION AND IN VITRO EVALUATION OF

MATRIX TABLETS CONTAINING PIOGLITAZONE

6. / Brief resume of the intended work:
6.1 Need for the study:
SUSTAINED RELEASE DOSAGE FORM:-
It is defined as the term used to identify drug delivery systems that are designed to achieve a prolonged therapeutic effect by continuously releasing medication over an extended period of time after administration of a single dose. The frequency of drug administration is reduced, patient compliance can be improved and drug administration can be made more convenient as well. A less obvious advantage implicit in the design of sustained release forms is that the total amount of drug administered can be reduced, thus maximizing availability with a minimum dose. The safety margin of high potency drugs can be increased and the incidence of both local and systemic adverse side effects can be reduced in sensitive patients. Overall, administration of sustained release forms enables increased reliability of therapy.1
DIABETES MELLITUS:-
It is a metabolic disorder characterized by hyperglycaemia, glycosuria, hyperlipemia, negative nitrogen balance and sometimes ketonemia. A wide spread pathological change is thickening of capillary basement membrane, increase in vessel wall matrix and cellular proliferation resulting in vascular complications like lumen narrowing, early atherosclerosis, sclerosis of glomerular capillaries, and peripheral vascular insufficiency.
There are two types of diabetes mellitus:
1. Type 1 Diabetes mellitus/ insulin dependent Diabetes mellitus is an
autoimmune disorder and is managed by insulin administration.
2. Type 2 Diabetes mellitus/ non insulin dependent diabetes mellitus, treatment
is initially dietary although oral hypo-glycaemic drugs usually become
necessary.
There are many classes of oral anti-diabetic agents. The objective of the treatment is to achieve euglycaemia, by using an ideal dosage regimen. An idealdosage regimen in the drug therapy of any disease is the one, which immediately attains the desired therapeutic concentration of drug in plasma and maintains it constant for the entire duration of treatment.2
Pioglitazone hydrochloride is orally administered insulin sensitizing thizolidinedione agent and highly selective agonist for the peroxisome proliferator – activated receptor gamma (PPAR). PPAR - receptor are found in tissues, which are target sites of insulin action e.g. adipose tissues, skeletal muscle and the liver. Activation of the PPAR nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism. Pioglitazone hydrochloride has an oral bioavailability of 83% and peak plasma concentrations of Pioglitazone hydrochloride are achieved in 2 – 2.5 hours. Elimination half of Pioglitazone hydrochloride is 3 to 7hrs6.
6.2 Review of the literature:

Kumar Get al.,formulated and evaluated matrix tablets of acarbose. Matrix tablet of acarbose were formulated as controlled release tablets employing HPMC and Eudragit in different concentration and combination. The sustained release behavior of the fabricated tablets was investigated. Control release matrix tablets containing 350 mg of acarbose was developed by using different drug and polymers combination. Tablet prepared by direct compression method were subjected to physical characterization. Formulation was optimized on the basis of acceptable properties and in-vitro drug release3.

Kamlesh et al., have developed an oral sustained release metformin tablet was

prepared by direct compression method, using hydrophilic eudragit RSPO and
RLPO alone or in combination with hydrophobic ethyl cellulose polymer as rate
Controlling factor. All the batches were evaluated for thickness, weight variation,
hardness and drug content uniformity and in-vitro drug release. Mean dissolution
time was used to characterize drug release rate from a dosage form and it indicated
the drug release retarding efficiency of polymer. When eudragit RSPO and RLPO
were used alone as the only retarding polymer, a sustained drug release pattern
were not observed while, inclusion of ethylcellulose in the matrix almost doubled
(12 h) the time required for releasing the drug. Kinetic modeling of in-vitro
dissolution profiles revealed that drug release mechanism was diffusion controlled
to anomalous type.4

Singh C et al., studied on formulation and evaluation of extended release tablet of Pioglitazone by melt granulation technique and concluded that, Pioglitazone is a potent and highly selective agonist for peroxyzome proliferators-activated receptor-gamma (PPAR). Pioglitazone has short biological half life of 3-5 hrs & is eliminated rapidly. Therefore Matrix type tablets of Pioglitazone were developed by using polymer such as Precirol ATO5, Campritol 888 ATO, Carnuba wax & Hydrogenated castor oil by melt Granulation technique. The tablet were initially placed in phosphate buffer at pH 7.4 at 8 hrs used dissolution apparatus USP-25.

Kumar Get al.,formulated and evaluated matrix tablets of acarbose. Matrix tablet of acarbose were formulated as controlled release tablets employing HPMC and Eudragit in different concentration and combination. The sustained release behavior of the fabricated tablets was investigated. Control release matrix tablets containing 350 mg of acarbose was developed by using different drug and polymers combination. Tablet prepared by direct compression method were subjected to physical characterization. Formulation was optimized on the basis of acceptable properties and in-vitro drug release7.

Basak SCet al.,developed the sustained release tablets containing metformin hydrochloride. Metformin hydrochloride was formulated as a hydrophobic matrix sustained release tablet employing wax materials and the sustained release behavior of the fabricated tablet was investigated. Sustained release matrix tablets containing 500 mg metformin HCl was developed using different bees wax combinations. The tablets were prepared by wet granulation technique. The formulation was optimized on the basis of acceptable tablet properties and in vitro drug release8.

Chowdary K.P.R.et al., they aimed to enhance the solubility and impart a controlled release pioglitazone -βCD matrix tablets; pioglitazone is an oral hypoglycemic agent which belongs to Class II of BCS with relatively short elimination half life. Inclusion complex of pioglitazone with β-cyclodextrin was prepared by kneading,co-precipitation, physical mixture and evaluated for its in-vitro release. The dissolution study of kneading complex shows significant increase in the drug release from kneading complex than pure drug and physical mixture9.

Rajendran N.N.et al.,The present study was to establish Bi‐layer tablets containing

Metformin HCl as sustained release and Pioglitazone HCl as immediate release
layer.The formulations (P6M7) having immediate release layer produces immediate
effect within 54 second followed by sustained release (97.35%) at 8 hrs and it
comparablewith innovator10.

Sameer Shafi et al., in the present work, sustained release (sr) sintered matrix tablets of diltiazem hydrochloride were prepared by trituration method using 4% and 8% hpmc k4m and hpmc k15m and then sintered. The prepared tablets were transferred to the sintering chamber and exposed to different sintering time like 3 hours and 6 hours. the release characteristics study was carried out in usp xxi model11.

Megha Sharma et al., Floating drug delivery systems (FDDS) are one of the important categories with gastric retentive behavior. Incorporation of the drug in a controlled release gastroretentive dosage forms, can remain in the gastric regionfor several hours which significantly prolong the gastric residence time, improve bioavailability, reduce drug waste and enhance the solubility of drugs. These systemsare useful to several problems encountered during the development of apharmaceutical dosageform. Although there are number of difficulties to beworked out to achieve prolonged gastricretention, a large number of companies are focusing toward commercializing this technique.12

6.3 Main objectives of the study:
The present work aim study the following objectives:
1)To evaluate the compatability studies of drug and excepient using FTIR studies.
2)To develop and formulate sustained release tablet of antidiabetic drug.
3)To evaluate the formulated dosage form by official in vitro studies.
4)To carry out short term stability studies on the most satisfactory formulation.
7. Materials and methods :
7.1 Source of data

The data will be obtained from the literature survey and internet source.

7.2 Method of collection of data (including sampling procedures if any):

The data will be collected from prepared formulations subjected to different evaluation techniques, estimation of drug content, in-vitro drug release, and stability studies.

Matirials:
Drug: Pioglitazone
Polymers: Methyal cellulose,Hydroxypropylmethyalcellulose,
Hydroxyethyalcellulose, sodiumcarboxymethylcellulose,eudragit RS,
Polyvinyl pyrrolidine(PVP),chitosan, PEG4000,
PEG6000 etc,
. Methods:
1.The matrix tablet prepared by using polymers methyl cellulose
Hydroxypropylmethyalcellulose,Hydroxyethyalcellulose,
sodiumcarboxymethylcellulose, Polyvinylpyrrolidine(PVP),chitosan, PEG4000,
PEG6000 etc.
2.The granules will be evaluated for angle of repose,compressibility index, &bulk
density.
3.The formulation will be characterized by different scanning calorimrty(DSC),X-
ray diffraction studies(XRD),scanning electron microscopy(SEM) & data will be
collected.
4.The effects of formulation variables on the drug release will be studied by
conducting dissolution experiments.
5.The stability studies of the formulation will be carried out as per ICH guide lines
&data will be collected.
7.3 Does the study require any investigation or interventions to be
Conducted on patients or other humans or animals?
- NO-
7.4 Has ethical clearance been obtained from your institution in case of
7.3?
- NO -

LIST OF REFERENCES:-

Lachman L, Lieberman A, Kanig J. The theory and practice of Industrial Pharmacy. Mumbai: Varghese publishing house 1990; 3: 430-431.
Tripathi KD. Essentials of Medical Pharmacology. New Delhi: Jaypee Brothers, Medical publishers (P) LTD 2003; 5: 235-249.
Kumar G, Juya V, Badoni PP. Formulation and evaluation of matrix tablets of acarbose. Drug Invention Today 2010;2(5):264-67.

4 Wadekar KJ, Kakde RB, Umekar MJ. Developnment of sustained release tablet of
metformine hydrochloride containing hydrophilic eudragit and ethyl cellulose polymer.
Int J Comp Phar 2011;2:01-06
5. Singh C, Jain AK, Agarwal K. Formulation and evaluation of extended release tablet of
Pioglitazone by melt granulation technique. Indian Drugs 2008 June; 45(6):461- 468.
6. KoichiroT. Overallmechanism behind matrix sustained release (SR) tablets
prepared with hydroxypropyl methylcellulose 2910. J Cntrl Rel1995; 35:59-66.
7. Kumar G, Juya V, Badoni PP. Formulation and evalution of matrix tablets of acarbose.
Drug Invention Today 2010;2(5):264-67.
8 Basak SC, Kumar SK, Ramalingam M. Design and release characteristic of sustained
release tablet containing metformin HCl. Brazilian J Pharm Sci 2008;3(44):477-83.
9 K.P.R. Chowdary1, P. Dwarakanadha Reddy2*Formulation development studies on β-
cyclodextrin complexation of pioglitazone matrix tablets International Journal of
Advances in Pharmaceutical Research 2011 ISSN: 2230 – 7583.
10 N.N.rajendran*,natarajan R. Subashini, Hitesh Patel .Formulation and evaluation of
sustained release bilayer tablets of metformin hcl and pioglitazone hcl international
journal of current pharmaceutical research issn- 0975-7066 vol 3, issue 3, 2011. 11 Sameer Shafiet al., Formulation and Evaluation of sintered matrix tablets of diltiazem
hydrochloride International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 3,
Issue 3, 2011.
12 Megha Sharma, Seema kohli Floating drug delivery of antidiabetic drugs: Int J
Pharm Bio Sci 2012 Oct; 3(4): (P) 456 – 471.
9 / Signature of the candidate: / BHAIRAPPA SHEDYAL
10 / Remarks of the guide: / Recommended.
11 / Name And Designation of:
11.1 Guide
11.2 Signature / Dr.C.C PATIL
Professor & Head
Department of Pharmaceutics,
BLDEA’s College of Pharmacy,
BLDEA’s University campus,
Bijapur-586 103
12 / 12.1 Co-Guide
12.2 Signature / NOT APPLICABLE
13 / 13.1 Head of the department
13.2 Signature / Dr.C.C PATIL
Professor & Head
Department of Pharmaceutics,
BLDEA’s College of Pharmacy,
BLDEA’s University campus,
Bijapur-586 103
14.1 Remarks of the Principal:
14.2 Signature / Recommended.
15 Remarks of the Guide:
The present work is aimed to formulate and evaluate the matrix tablet form selected anti diabetic drugs,pioglitazone. It is member thizalidinediones which is used from diabetes mellitus type-2. It stimulates the nuclear receptor peroxisoneproliferator activated receptor gamma. When administered to orally, 83% of bioavailabilityis obtained with half life of 3to7hrs. It short acting with rapid onset of action. The drug is likely to absorbed or degraded in stomach & small intestine. Therefore it is preferred to use in the matrix dosage form.
The proposed study can be carried out in the laboratory.
Dr. C.C PATIL
Professor & HOD