FOR
EXTENDED RELEASE TABLETS
M.PHARM DISSERTATION PROTOCOL
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA.
BY
MUTHINENI SUSRITH
I M.PHARM
UNDER THE GUIDANCE
JAYA RAJ
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY
KARNATAKA COLLEGE OF PHARMACY
BENGALURU-560064
(2011-2012)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / NAME OF THE CANDIDATE AND ADDRESS / MUTHINENI SUSRITHKARNATAKA COLLEGE OF PHARMACY
# 33/2 THIRUMENAHALLI
HEGDE NAGAR MAIN ROAD
BENGALURU-560064.
PERMANENT ADDRESS
S/O M. SAMBASIVARAO
HOUSE NO:2-79
PEDAKANCHERLA(POST),
VINUKONDA(MD),
GUNTUR(DT),
ANDHRA PRADESH-522
2. / NAME OF THE INSTITUTE / KARNATAKACOLLEGE OF PHARMACY
# 33/2 THIRUMENAHALLI,
HEGDE NAGAR MAIN ROAD,
BANGALORE-560064
3. / COURSE OF THE STUDY & SUBJECT /
MASTER OF PHARMACY IN PHARMACEUTICALTECHNOLOGY
4. / DATE OF ADMISSION TO THE COURSE / 21st SEPT., 2011.5. / TITLE OF THE TOPIC:
FORMULATION AND EVALUATION OF PHOSHODIESTERASE INHIBITORS FOR
EXTENDED RELEASE TABLETS
6. / BRIEF RESUME OF THE INTENDED WORK:
ACTIVIT
6.1 Need For The Study:
Among the different routes of administration, the oral route of administration continues to be the most preferred route due to various positives including ease of ingestion, avoidance of pain, versatility and most importantly patient compliance. The different dosage forms include tablets and capsules.
Tablets as solid dosage forms are more popular because of advantages like, accurate dosage, self medication, pain avoidance. Tablet is mostly preferred by the manufacturers also, Because almost all drug molecules can be formulated as tablets with less stability problems and process of manufacturing of tablets too is very simple, and flexible.
Heart failure is a progressive syndrome resulting from the heart’s inability to adequately perfuse and oxygenate peripheral tissues. Common causes of heart failure include myocardial infarction, ischemic heart disease, hypertension, valvular, heart disease, and cardiomyopathy. Heart failure can cause a number of symptoms including shortness of breath, coughing, chronic venous congestion, ankle swelling, and exercise intolerance.
Heart failure is a common, costly, disabling, and deadly condition, calcium levels in the heart majorly improves hearts contractility nature and thus promotes its efficient functioning.
Phosphodieseterase enzyme in the heart break down cAMP available in the heart reducing calcium entry inside the heart and thus reducing the contractility of heart, making it weak. Present study deals with inhibiting the phosphordiesterase enzyme in the heart and thus increasing cAMP levels in the heart, improving the contractility of heart using an extended release tablets.
6.2 Review of Literature:
· Carla Sa´nchez-Lafuente et al., Didanosine extended release matrix tablets were formulated by direct compression using blends of two insoluble polymers like eudragit rs-pm, and ethocel 100 and statistical experimental design was used to evaluate influence of some process and formulation variables, with final goal of drug release behavior optimization.1
· Grzegorz Garbacz et al., Nifedipine extended release tablets of different strengths were checked for dissolution profile in various dissolution apparatus using acetate buffer and gastro intestinal fluid etc2.
· Hind Al-Zein et al., A sustained release tablet for a less soluble drug in alkaline medium like nicardipine a calcium channel blocking drug was prepared using solid dispersion methods like evaporation method, kneading method using glyceryl monosterate as inert waxy substance and peg as channeling agent and beta-cyclodextrin in various ratios, and characterized by x-ray diffractometry, ir, dsc etc.3
· Maggi L et al., The extended release matrix formulations were prepared for nifedipine using hpmc (or) polyethylene oxide as retarding polymers in matrix and checked for photo stability after exposing to uv light the polyethylene oxide used formulation have shown remarkable increase in drug release rate compared to hpmc matrix tablets.4
· Verma K et al., Extended release formulation for isosorbide mono nitrate was developed using osmotic technology with various excepients like pvp, hpmc, and pore former from which the drug is released, here the drug release was inversely proportional to membrane weight and directly proportional to pore former in the membrane which is characterized by scanning electron microscopy and formulation also evaluated for burst strength, osmotic pressure etc5.
· Shinichiro Tajiri et al., Extended release tablets of cevimeline were prepared as simple matrix tablets and press coated tablets using hydroxypropyl cellulose as rate controlling polymer and shown that press coated tablets are better than simple matrix ones having slower dissolution and linear curve profile with out any effect in gastro intestinal ph by conducting dissolution in paddle apparatus at 200-500 rpm.6
· Sung-Hyun Park et al., A chitosan and carbopol inter polymer complex was formed using a precipitation method in acidic solution and complex was characterized by FT-IR, DSC, turbidity measurements for checking how a complex forms, to check thermal characteristics of complex, to check complexation ratio of carbopol/chitosan respectively.7
· Weitschies W et al., Bioavailability of amoxicillin and clavulanic acid from extended release tablets was checked by pharmacokinetic study using magnetic marker monitoring,the results shown that amoxicillin have reduced bioavailability due to earlier gastric emptying, prolonged gastric residence of clavulanic acid in proximal part of stomach reduced its bioav ailability, so the drug is checked for pharmacokinetic parameters for good extended release in body.8
· Wilson S. Colluci et al., Efficacy of phosphodiesterase inhibition by milrinone a phosphor diesterase inhibitor drug is checked by combining with angiotensin conversion enzyme inhibitors like captopril in patients with heart failure9.
· Yaw-Bin Huang et al., Once daily propanolol extended release tablet formulation was prepared using hydroxypropyl cellulose, micro crystalline cellulose, lactose in different ratios. optimized Hind Al-Zein formulation using the above was prepared by using response surface methodology and proved mechanism of drug release from hpmc matrix tablets was a non fickian diffusion.10
6.3 Objective of the Study:
The objectives of proposed study are
1. Development of an ideal extended release tablets.
2. To carry out pre formulation studies.
3. Preparation of extended release tablets by using various polymers.
4. Evaluation of formulated extended release tablets tablets.
5. To carry out the stability studies for selected product.
7. / Materials & Methods:
7.1 Source of Data:
a. Literature survey and internet source.
b. Digital library, R.G.U.H.S, Bangalore.
c. Library, Karnataka College of Pharmacy.
7.2 Method of Collection of Data (including sampling procedure, if any) :
Data on drugs will be collected through literature survey and from physiochemical database. Extensive pre formulation trials would provide the basis of selection the excipients and system for final formulation development.
7.3 Materials
Ø Drug : phosphodiesterase inhibitor drug will be procured/obtained form suitable pharma grade manufacturer.
Ø All other chemicals will be used of analytical grade.
7.4 Methods
I. Preformulation studies
a. Preliminary Morphological Studies
b. Compatibility studies
II. Preparation Of Granules
a. Wet granulation
b. Dry granulation
c. Direct compression
III. Evaluation studies
1. Evaluation of Granules
a. Particle size and shape analysis
b. True density
c. Bulk density
2. Evaluation of Tablets
a. Thickness
b. Weight variation Test
c. Drug content
d. Hardness
e. Friability
f. Disintegration time
g. In vitro dissolution studies
h. Content uniformity
i. Assay
IV Stability studies as per the ICH guidelines.
7.3 Method of Screening:
7.5 Does the study require any investigations or interventions to be conducted
On patients or other human or animals? If so please describe briefly
-NOT APPLICABLE-
7.6 Has the Ethical Clearance been obtained from your Institution in case of 7.5?
-NOT APPLICABLE-
8. / LIST OF REFERENCES:-
1. Carla Sa´nchez-Lafuente et al., Didanosine extended-release matrix tablets, ijp 2008; 237: 107-118.
2. Grzegorz Garbacz et al., Comparison of dissolution profiles obtained from nifedipine extended release tablets, European Journal of Pharmaceutical Sciences 2009; 38: 147–155
3. Hind Al-Zein a, Khalil Sakeer b, Fars K, Alanazi cd. Designing an extended release waxy matrix tablet. Saudi Pharmaceutical Journal 2011; 19: 245–253.
4. Maggi L, Ochoa Machiste E, Fasani E, Albini A, Segale L, Conte U. Photostability of extended-release matrix formulations. European Journal of Pharmaceutics and Biopharmaceutics 2003; 55: 99–105.
5. Verma K, Aditya M, Kaushal, Sanjay Garg. Development and evaluation of extended release formulations of isosorbide mononitrate based on osmotic technology. International Journal of Pharmaceutics 2003; 263: 9–24.
6. Shinichiro Tajiri , Taro Kanamaru, Kamada Makoto, Tsutomu Konno, Hiroaki Nakagami. Dosage form design and in vitro/in vivo evaluation of cevimeline extended-release tablet formulations. International Journal of Pharmaceutics 2010; 383 : 99–105.
7. Sung-Hyun Park, Myung-Kwan Chun, Hoo-Kyun Choi . Preparation of an extended-release matrix tablet using chitosan/Carbopol interpolymer complex.International Journal of Pharmaceutics 2008 ; 347 : 39–44.
8. Weitschies W et al., Bioavailability of amoxicillin and clavulanic acid from extended release tablets. European Journal of Pharmaceutics and Biopharmaceutics 2008; 70 : 641–648.
9. WILSON S et al., Efficacy of Phosphodiesterase Inhibition With Milrinone in Combination With Converting Enzyme Inhibitors in Patients With Heart Failure. JACK 1993 ; 22: 113A-8A.
10. Yaw-Bin Huang, Yi-Hung Tsai, Wan-Chiech Yang, Jui-Sheng Chang, Pao-Chu Wu, Kozo Takayama. Once-daily propranolol extended-release tablet dosage form: formulation design and in vitro/ in vivo investigation European Journal of Pharmaceutics and Biopharmaceutics 2004 ; 58 : 607–614.
9. / Signature of the Candidate /
(MUTHINENI SUSRITH )
10. / Remarks of the Guide:
The topic selected for dissertation is satisfactory. Adequate equipment and chemicals are available to carry out the project work.
11. / Name & Designation (in BLOCK LETTERS)
11.1 Guide / MR. JAYA RAJ
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY
KARNATAKA COLLEGE OF PHARMACY
# 33/2 THIRUMENAHALLI
HEGDE NAGAR MAIN ROAD
BANGLORE-560064.
11.2 Signature of Guide /
(MR. JAYA RAJ)
.)
11.3 Co-Guide /
-NA-
11.4 Signature of Co-Guide
/ -NA-
11.5 Head of the Department / Dr.B. PRAKASH RAO
PROFESSOR AND HEAD OF
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY
KARNATAKA COLLEGE OF PHARMACY
# 33/2 THIRUMENAHALLI
HEGDE NAGAR MAIN ROAD
BANGLORE – 560064
11.6 Signature of HOD: /
(DR. B.PRAKASH RAO)
12 / 12.1 Remarks of the principal / All the required facilities will be provided to carry out dissertion work under the supervision of the Guide.
12.2 Principal/DIRECTOR / DR.K. RAMESH.
Director
Karnataka College of Pharmacy
#33/2, Thirumenhalli
Hegde nagar main road
Bengaluru-64.
12.3 Signature of the Principal/DIRECTOR / (DR.K. RAMESH)
7