“formulation and evaluation OF MICROSPHERE OF Anti-asthmatic drug.”
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE
SUBMITTED BY
THUMAR NAIMISH R.
DEPARTMENT OF PHARMACEUTICS
UNDER THE GUIDANCE OF
Mrs. A.GEETHA LAKSHMI,
ASST. PROFESSOR.
THE OXFORD COLLEGE OF PHARMACY
HONGASANDRA, BANGALORE-68
KARNATAKA
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / Name of the Candidate and Address: / THUMAR NAIMISH RAVJIBHAIA.Permanent Address:
Punit Nagar, Jetpur Road,
Street no. 9,
“SHIVAM”, Gondal -360311
Gujarat.
B.Postal Address:
THUMAR NAIMISH RAVJIBHAI
The oxford College of Pharmacy
6/9 1st cross,
Begur main road, Hongasandra,
Bangalore – 560068
Karnataka.
2. / Name of the Institute: / The oxford College of Pharmacy
6/9 1st cross,
Begur main road, Hongasandra,
Bangalore – 560068
Karnataka.
3. / Course of Study and subject: / Master of Pharmacy (Pharmaceutics)
4. / Date of Admission to the Course: / 08-12 -2011
5. / Title of the Project:
“formulation and evaluation OF MICROSPHERE OF ANTI-ASTHMATIC drug.”
6. / Brief Resume of the Intended work:
6.1 Need for the Study:
· Asthma is a heterogeneous common chronic condition characterized by endobronchial inflammation with consequent bronchial hyper responsiveness. This leads to variable airflow obstruction and typical symptoms such as cough, breathlessness, chest tightness, wheezing and reduced exercise tolerance1.
· Asthma is one of the leading diseases in the world and needs some serious attention. Asthma is estimated to affect as many as300 million people worldwide and 15 million people in India. It can lead to various complications like bronchospasm, respiratory failure and chronic obstructive pulmonary disease (COPD) etc2.
· Anti-asthmatic drugs like Terbutaline sulphate (TS) and Salbutamol sulphate (SS) are selective β2-adrenergic agonist which acts on β2- adrenoreceptor for the treatment of mild to severe asthma2.
· Anti-asthmatic drug has short biological half-life of about 3-6 hrs. It is readily metabolized in the gut wall when given orally. It has a short duration of action and poor bioavailability of only 14.8%. These problems can be solved by using a controlled drug delivery system like microspheres which can deliver the drug for a sustained period of time3.
· Microspheres provide sustained release over a prolonged period of time and better bioavailability, which reduces dosing frequency, side effects and thereby increases patient compliance. The smaller size and spherical shape of microspheres increases the surface area which increases the bioavailability of the dosage form2.
· Microspheres are spherical microscopic particles having a size range of 1 - 1000μm and it can define as a monolithic sphere or therapeutic agent distributed throughout the matrix.
· The present work describes the formulation and evaluation of microsphere of an anti-asthmatic drug.
6.2 Review of Literature:
1. The work has been done on Aceclofenac microsphere using rosin by o/w emulsion solvent evaporation technique and it was concluded that the drug entrapment efficiency of prepared microspheres were affected only by the drug: polymer ratio. The emulsifier concentration and organic phase volume influenced the particle size distribution of microspheres4.
2. Double Emulsion-solvent evaporation method was used for Diclofenac potassium (DP) microspheres with ethyl cellulose (EC) and Eudragit polymer and it was concluded that Eudragit microspheres showed good batch to batch reproducibility with respect to yield, particle size and entrapment efficiency when compared to Ethyl cellulose microspheres. The volume of the internal phase of the primary emulsion and the volume of the external phase of the secondary emulsion are the area of concentration and which affects significantly, the characteristic of microspheres5.
3. The work was reported on Ibuprofen microspheres by using ethyl cellulose as carrier which is prepared by the solvent evaporation method and it was concluded that it is a best method for preparing ibuprofen loaded microspheres from its higher percentage yield. Higher percentage of loading was obtained by increasing the amount of ibuprofen with respect to polymer6.
4. The floating microspheres of famotidine showed good incorporation efficiency, good buoyancy and prolonged drug release by solvent evaporation (Oil-in-water emulsion) technique using hydroxypropyl methylcellulose (HPMC) and Ethylcellulose (EC) as the rate controlling polymers. The drug release from the floating microspheres matrix was controlled by the polymer proportion7.
5. The preparation and characterization of Ca-alginate microspheres obtained by a new procedure from alginic acid, treated with an excess of NaOH and subsequently with a very concentrated solution of CaCl2 and concluded that the micro particles with a high degree of cross linking can be rapidly produced using a very simple procedure. They are not friable, and with a low swelling tendency and presenting a high degree of cross linking, a high dry-matter content and a low specific solvent uptake when compared to macro reticular gels8.
6. The study was done on Norfloxacin microspheres (NM), by using various polymers like Carbopol-934, Sodium Carboxy Methyl Cellulose (SCMC) using different drug : polymer ratios by using multiple emulsion solvent evaporation technique and concluded that drug loaded microspheres appear to be a suitable delivery system for Norfloxacin and may help to reduce dose of drug and frequency of administration9.
7. The research work was done on the floating microspheres of Stavudine were prepared by emulsion solvent diffusion method using Eudragit RS 100 as a rate controlling polymer and the prepared formulations released Stavudine in a controlled manner for over 12 h and thus may be reduce frequency of dosing, thereby minimizing the occurrence of side effects, increase residence time in stomach and increase the effectiveness of the drug10.
8. The study aimed on Albumin microspheres of hydralazine hydrochloride were prepared by emulsion cross-linking method by using glutaraldehyde as cross-linking agent and the formulated microspheres can be controlled by varying polymer concentration and volume of glutaraldehyde and developed microspheres could be useful for once-a-day antihypertensive therapy11.
9. The research work was represented on Gelatin microspheres containing ofloxacin were prepared by coacervation phase separation method and concluded that microsphere was able to sustain the release effectively12.
10. The work was reported on microspheres of Terbutaline sulphate (TBS) by water-in oil- in-water (w/o/w) double emulsion solvent diffusion method using ethyl cellulose and it was concluded that by this method the entrapment efficiency was still lower compared to the same process reported for other hydrophilic drugs13.
11. The work was done gelatin microspheres containing lactic acid were prepared by the polymerization technique using glutaraldehyde as the cross-linking agent and it was concluded that the In vitro drug release experiments showed a distinct biphasic release pattern that may be desirable for topical drug delivery and the desired lactic acid release rate can be achieved by controlling the amount of the cross-linking agent (glutaraldehyde) and the duration of cross-linking time14.
12. The study was done on floating microspheres of Ranitidine Hydrochloride with HPMC 15 cps and Eudragit E‐100 and concluded that with both acrylic and hydrophilic polymers the GI retention can be enhanced and the frequency of administration can be decreased. This gives a signal to extending this approach to similar combinations of drugs used in clinical practice so as to improve bioavailability of poorly absorbed drugs in GIT15.
6.3 Objective of the Study:
· To formulate and evaluate the microsphere of anti-asthmatic drug.
· To carry out preformulation study.
· To study the effect of polymer concentration on the drug release profile.
· To carry out short term stability studies.
7.0 Materials and Method:
· The drug of choice proposed to take up for work under the class of anti-asthmatic is Terbutaline sulphate.
· The materials, choice of excipients, and the suitable batch formulae will be decided after the compatibility studies are assessed by FTIR studies.
Method of preparation of microsphere16:
ü Solvent evaporation technique.
ü Single Emulsion polymerization technique.
ü Phase separation coaservation method.
7.1 Source of Data:
Data was obtained from review of literature from the:
Ø library of oxford college of pharmacy,
Ø Jgate @ helinet, RGUHS Bangalore,
Ø world wide web site,
Ø science direct,
Ø books
o Essentials of medical pharmacology by KD Tripathi,
o Targeted & controlled drug delivery Novel carrier system by S.P.Vyas and R.K.Khar
o Pharmaceutical product development by N.K.jain
o Controlled drug delivery concept & advance by S.P.Vyas and Roop K. Khar
7.2 Method of collection of data:
Ø Formulation of microsphere, using different concentration of polymer.
The solid dosage forms are performed by two phases. They are as follows;
· Preformulation study
· Evaluation
Under Preformulation study it includes;
· Compatibility studies using FTIR
· Bulk density
· Angle of repose
Evaluation Parameters:
· Size and shape
· Weight variation test
· Entrapment efficiency
· Content uniformity
· Dissolution test
· Short term Stability studies
7.3 Does the study require any investigations of interventions to be conducted on patients or other human or animals? If so please describe briefly?
NO
7.4 Has ethical clearance been obtained from your institute in case of as above?
NA
8. / List of References:
1. Tripathi KD. Essentials of medical pharmacology. 6th ed. New Delhi: jaypee brother’s medical publishers (p) LTD; 2008.p.214-6.
2. Chakraborty A, Mathew TS, Mathappan R, Kamalakkannan V. Formulation and evaluation of salbutamol sulphate microspheres by solvent evaporation method. JAPS 2011;01(05):133-7.
3. Chanda R, Roy A, Bahadur S, Saha S, Das S, Choudhury A. Formulation of terbutaline sulphate mucoadhesive sustained release oral tablets from natural materialsand in vitro-in vivo evaluation. AJPS 2010;5(4):168-74.
4. Lakshmana Prabu S, Shirwaikar AA, Shirwaikar A, Kumar A. Formulation and evaluation of sustained release microspheres of rosin containing aceclofenac. Ars Pharm 2009;50(2):51-62.
5. Dineshbabu G, Reddy BVV, Rajeev Chandra S, Subhash Chandra A, Vinodkumar KH. Preparation and evaluation of ethyl cellulose and eudragit based microspheres of diclofenac potassium using double emulsion-solvent evaporation method. Int J Curr Pharm Res 2011;3(4):64-7.
6. Sudhamani T, Reddy KN, RaviKumar VR, Revathi R, Ganesan V. Preparation and evaluation of ethyl cellulose microspheres of ibuprofen for sustained drug delivery. IJPRD 2010 Oct 19;2(8):119-25.
7. Singh B, Kanoujia J, Pandey M, Saraf SA. Formulation and evaluation of floating microspheres of famotidine. Int.J. PharmTech Res 2010 April-June;2(2):1415-20.
8. Fundueanu G, Esposito E, Mihai D, Carpov A, Desbrieres J, Rinaudo M et al. Preparation and characterization of Ca-alginate microspheres by a new emulsification method. Int. J. Pharmaceut 1998;11–21.
9. Sindhuri P, Purushotaman M. Formulation and evaluation of norfloxacin microspheres using different polymers. Int. J. Pharm & Ind. Res 2011 Jan-Mar;01(01):32-5.
10. Josephine LJ, Mehul RT, Wilson B, Shanaz B, Bincy R. Formulation and in vitro evaluation of floating microspheres of anti-retro viral drug as a gastro retentive dosage form. IJRPC 2011;1(3):519-27.
11. Nanjwade BK, Bechra HM, Nanjwade VK, Derkar GK, Manvi FV. Formulation and characterization of Hydralazine hydrochloride biodegraded microspheres for intramuscular administration. JBABM 2011;3(1):32-7.
12. Arunachalam A, Rathinaraj BS, Subramanian, Choudhury P, Reddy AK, Md Fareedullahs MD. Preparation and evaluation of ofloxacin microspheres using natural gelatin polymer. IJABPT 2010 May-July;1(1):61-7.
13. Kotadiya R, Patel V, Patel H, Salaniya B. Evaluation of terbutaline sulphate encapsulated ethylcellulose microspheres: a factorial approach. Int.J. PharmTech Res. 2009 Oct-Dec;1(4):1271-78.
14. Dinarvand R, Mahmoodi S, Farboud E, Salehi M, Atyabi F. Preparation of gelatin microspheres containing lactic acid – Effect of cross-linking on drug release. Acta Pharm 2005;55:57-67.
15. Punitha K, Khadhir S, Ravichandiran V, Umadevi SK, Vaijayanthi V, Padmapriya S et al. Intragastric floating drug delivery system of ranitidine hydrochloride: formulation and evaluation. Int J Pharm Pharm Sci 2010;2(4):105-8.
16. Kedar Prasad M, Dangi JS, Samal PK, Namdeo KP. Recent advances in microspheres manufacturing technology. IJPT 2011 March;3(1):854-93.
9. / Signature of the Candidate: / (THUMAR NAIMISH)
10. / Remarks of the Guide:
“formulation and evaluation OF MICROSPHERE OF ANTI-ASTHMATIC drug” to be carried out by THUMAR NAIMISH RAVJIBHAI of M.Pharm has been discussed and worked under my direction and supervision as the official guide. The program and research work envisaged is of great importance in the modern field of pharmaceutical research.
11. / Name and Designation of
11.1 Guide: / Mrs. A.GEETHA LAKSHMI,
ASST. PROFESSOR
11.2 Signature of Guide:
11.3 Co-Guide if any: / NA
11.4 Signature of Co-Guide: / NA
11.5 Head of Department: / Dr. Prof. Kalyani Prakasam,
Professor and HOD,
Dept. of Pharmaceutics.
11.6 Signature of HOD:
12. /
12.1 Remarks of the Principal:
12.2 Signature of Principal: / DR. PADMAA M. PAARAKH
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