“FORMULATION AND EVALUATION OF FAST DISINTEGRATING
SUBLINGUAL TABLETS OF ANTI HYPERTENSIVE DRUG”
MASTER OF PHARMACY DISSERTATION PROTOCOL
SUBMITTED TO THE
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA, BANGALORE.
BY
SRINIVAS HEBBAR
M.PHARM – I
Under The Guidance of
Dr.A.R. SHABARAYA M. Pharm., Ph.D.
DEPARTMENT OF PHARMACEUTICS.
SRINIVAS COLLEGE OF PHARMACY, VALACHIL, MANGALORE – 574143
2010-2012
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. / Name of the Candidate and Address: / MR. SRINIVAS HEBBAR.1stYEAR M.PHARM, DEPT. OF
PHARMACEUTICS,
SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, MANGALORE-574143.
2. / Name of the Institution: / SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, FARANGIPETE POST, MANGALORE-574143.
3. / Course of Study and Subject: / MASTER OF PHARMACY.
(PHARMACEUTICS)
4. / Date of Admission: / 29/10/ 2010.
5. / Title of the Project:
FORMULATION AND EVALUATION OF FAST DISINTEGRATING SUBLINGUAL TABLETS OF ANTI HYPERTENSIVE DRUG.
6.
7.
8. / Brief Resume of the intended work:
6.1 Need of the study:
Systemic drug delivery through the sublingual route had emerged from the desire to provide immediate onset of pharmacological effect. Dysphagia (difficulty in swallowing) is a common problem of all age groups, especially elderly, children and patients who are mentally retarded, uncooperative, nauseated or on reduced liquid intake/diets have difficulties in swallowing these dosage forms.
Sublingual administration of the drug means placement of the drug under the tongue and drug reaches directly in to the blood stream through the ventral surface of the tongue and floor of the mouth. The drug solutes are rapidly absorbed into the reticulated vein which lies underneath the oral mucosa, and transported through the facial veins, internal jugular vein and braciocephalic vein and then drained in to systemic circulation1.
Hypertension is a disease that usually needs rapid action. Fast disintegrating tablets of anti-hypertensive drugs avoids hepatic metabolism due to pregastric absorption of drug, which reduces the dose and increase bioavailability. The medication as bitter pills has changed by use of flavours and sweeteners in fast disintegrating tablets of anti-hypertensive drugs and easy to administer for paediatric, geriatric and institutionalized patients. Fast disintegrating tablets of anti-hypertensive drugs results in quick dissolution and rapid absorption which provide rapid onset of action2.
Disintegrants are substances or mixture of substances added to the drug formulation that facilitate the breakup or disintegration of tablet or capsule content into smaller particles that dissolve more rapidly. Recently new materials termed as superdisintegrant have been developed to improve the disintegration processes. The disintegrants have the major function to affect the efficiency of the tablet binder and the physical forces that act under compression to form the tablet.3
In present study, attempt is made to prepare fast disintegrating sublingual tablets containing an anti-hypertensive drug along with various super disintegrants.
6.2 – Review of literature:
· Vineet B, et al. have formulated and evaluated fast disintegrating sublingual tablets of Amlodipine Besylate. This is used in potential emergency treatment of angina and hypertension. The tablets were evaluated for weight variation, hardness, friability, wetting time, disintegrating time, dissolution study. The above study shows that dissolution rate of Amlodipine Besylate can be enhanced to a great extent by direct compression technique with the addition of super disintegrants4.
· Rameshwari S, et al. have formulated and evaluated of Nifedipine sublingual tablet. Nifedipine for the potential emergency treatment of anginal pain and hypertension. In this study three different groups of formulation with variation on tablet excipients were prepared by direct compression method. In this study weight variation, hardness, friability, drug content, disintegration time, and dissolution rate are evaluated for each formulation and found satisfactory5.
· Suresh VK, et al. have formulated of taste masked fast disintegrating Lisinopril tablets. Lisinopril used in the treatment of hypertension and congestive heart failure. In this study the influence of super disintegrating like cross povidone, croscaremellose sodium on disintegration time, wetting time and water absorption ratio were studied. In this study cross povidone showed better performance in disintegration time when compared to croscaremellose sodium. Here the acceptable taste can be made6.
· Sindhu A, et al. have formulated and optimize sublingual tablets of Rabeprazole Sodium. It is a class of proton pump inhibitors used in the treatment of acid peptic disorder. In this they prepared the tablet by wet granulation method. The effect of formulation variable on wetting time and invitro dispersion time can be studied by applying optimization technique. Here super disintegrating like cross povidone, croscaremellose sodium, etc is used7.
· Noushin B, et al. have formulated and optimize of Captopril sublingual tablet using D-optimal design. Captopril which is an effective drug in the treatment of hypertension. Here the tablets wereprepared by direct compression method using different ingredients such as poly vinyl pyrrolidone, starch1500, sodium starchglycolate, etc. According to this study PVP has a significant effect on tablet hardness; on the other hand, fast disintegrating Captopril sublingual tablets could be achieved by using higher amount of sodium starchglycolate as well as starch15008.
· Narendra C, et al. have formulated and evaluated the sublingual tablet containing Terbutaline Sulphate. Here the formulation is prepared by wet granulation technique. In this study the effect of formulation variable on crushing strength, percentage friability and disintegrating time by applying the computer optimization technique. Disintegrating agent such as MCC, Crospovidone, etc. are used9.
· Abeer MA, et al. have demonstrated the effect of pH on sublingual absorption of Oxycodone Hydrochloride. This study was to develop a sublingual spray drug delivery formulation of Oxycodone and evaluate the effect of formulation pH on sublingual absorption for acute pain. Here the rabbit is used as an animal model. The formulation pH appears to have no significant effect on sublingual absorption Oxycodone sprays formulation10.
6.3 – Objectives of the study:
1. To formulate anti-hypertensive fast disintegrating sublingual tablets by using different super disintegrants.
2. To achieve increased bioavailability and quick onset of action.
3. To evaluate the formulated anti-hypertensive sublingual tablets.
4. To check drug excipients compatibility.
Materials and Methods:
Materials:
1. Drug : Selective Anti-hypertensive drug.
2. Disintegrants: Kollidon CL, Sodium Starch Glycolate,
Croscarmellose Sodium, etc.
3. Excipients : Dicalcium Phosphate, Poly vinyl Pyrrolidone, talc, Aspartame
and magnesium stearate, etc.
Methods:
Sublingual tablets of anti-hypertensive drug can be prepared by direct compression method4, 5.
7.1 Source of data:
Review of literature from
a) Journals such as
Ø International Journal of ChemTech Research.
Ø International Journal of Pharma Professional’s Research.
Ø Journal of Chemical and Pharmaceutical Research.
Ø Indian Journal of Pharmaceutical Sciences.
Ø Journal of Global Pharma Technology.
Ø International Journal of Pharmaceutical Sciences Review and Research.
Ø International Journal of Pharmacy and Pharmaceutical Sciences.
Ø Journal of Pharma Research.
b) Internet Browsing.
c) Laboratory based studies.
7.2 – Method of Collection of Data:
1. An Overview of sublingual Tablets.
2. Formulation of sublingual Tablets.
3. Evaluation of formulated anti-hypertensive sublingual tablets, as follows:
Ø Drug-Excipient interaction studies4
Ø Hardness4,5,
Ø Friability4,6,7
Ø Weight variation5,9
Ø Drug content5,6,7
Ø Wetting time and Water absorption ratio4,6,7
Ø In-vitro disintegration time4,5,6
Ø In-vitro dissolution study4,5,6
Ø Stability studies as per ICH guidelines
· Drug and excipients interaction:
Ø By F.T.I.R Spectroscopy4,6
· In vitro drug release study:
Ø USP II dissolution by paddle method4,5
7.3. Does the study require any investigations or interventions to beconducted on patients or other humans or animals? If so, please describe briefly.
- Not applicable.
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
- Not applicable.
List of references:
1. Neha N, Jyoti S. Sublingual mucosa as a route for systemic drug delivery. Int J Pharm & Pharm Sci.2011;3(2):18-22.
2. Jain CP, Naruka PS. Formulation and evaluation of fast dissolving tablets of Valsatran. Int J Pharmacy Pharm Sci.2009;1(1):219-26.
3. Santanu C, MadhusmrutiK, Satyaprakash S, Niranjan CP. Comparative study on effect of natural and synthetic superdisintegrants in the formulation of fast dissolving tablets. Int J of Green Pharm.2008;2(1):22-25.
4. Vineet B, Vikesh S, Narendra G, Salim MD, Sharma PK. Formulation and evaluation of fast disintegrating sublingual tablets of Amlodipine Besylate using different super disintegrants. IntJ Pharm & Pharm Sci.2010;2(3):89-92.
5. Rameshwari S, Jeya AJ. Formulation and Evaluation of Nifedipine sublingual tablets. Asian J Pharm & clinical Res.2009;2(3):44-48.
6. Suresh VK, Ranjit KP, Basavaraj, Someshwara RB, Ramesh B, Ashok KP. Effect of superdisintegrants on Formulation of taste masked fast disintegrating Lisinopril tablets. Int J curr Pharm Res.2011;3(1):11-14.
7. Sindhu Abram, Basavaraj BV, Bharath S, Deveswaran R, Sharon F, Madhavan V.Formulation and Optimization of Sublingual tablets of Rabeprazole Sodium. Int J Pharm Sci Res.2010;5(2):50-54.
8. Noushin B, Naghmesh H, Seyed MF, Bijan S. Formulation and optimization of Captopril sublingual tablet using D-optimal Design. Iranian J Pharm Res.2008;7(4):259-67.
9. Narendra C, Srinath MS, Prakash BR. Formulation and evaluation of sublingual tablet containing Terbutalin Sulphate optimisation and invivo studies. Ars Pharm.2005;46(2):139-58.
10. Abeer M A, Ahmad HM, Peter AC. Effect of PH on sublingual absorption of Oxycodone Hydrochloride. AAPS Pharm Sci Tech.2006;7(1) E1-E5.
11. NoushinB, Naghmeh H, Seyed Mohsen F, Bijan S. Development and optimization of a sublingual tablet formulation for Physostimine Salicylate. Acta Pharm.2009;59(1):301-12.
12. Mutasem M, Rawas-Qalaji, Estelle FR. Simons, Keith J, Simons.Fast disintegrating sublingual tablet: Effect of Epinephrine load on tablet characteristics.AAPS Pharm Sci Tech.2006;7(2):E1-E7.
13. Mallikarjuna SC, Prasad DVK, Gupta VRM.Development of fast dispersible Aceclofenac tablet: Effect of functionality of superdisintegrants. Ind J Pharm Sci.2008;70(2):180-5.
14. Shirsand SB, Sarasija S, Swamy PV, Para MS, Nagendra KD. Formulation design of fast disintegrating tablets using disintegrant blends. Ind J Pharm Sci.2010;72(1):130-3.
9. / Signature of the candidate / (SRINIVAS HEBBAR)
10. / Remarks of the Guide / The work, which is assigned to
Mr. SRINIVAS HEBBAR is under my guidance.
11. / 11.1 Name and Designation of the
Guide / Dr.A.R. SHABARAYA M.Pharm., Ph.D.
Principal and Director,
Srinivas College of Pharmacy
Valachil, Mangalore- 574143.
11.2 Signature
11.3 Name and Designation of the
Co-Guide / ------
11.4 Signature / ------
11.5 Head of the Department / Dr. A. R. SHABARAYA M.Pharm.,Ph.D.
Principal and Director,
Srinivas College of Pharmacy,
Valachil, Mangalore- 574143.
11.6 Signature
12. / 12.1 Remarks of the Principal / Recommended and forwarded for favourable consideration.
12.2 Signature / Dr. A. R. SHABARAYA