“STUDY OF FORMULATION VARIABLES OF PROMETHAZINE HYDROCHLORIDE LOZENGES”
MASTER OF PHARMACY DISSERTATION PROTOCOL
SUBMITTED TO THE
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA, BANGALORE.
BY
BHATT HEER SURENDRA
M.PHARM – I
Under The Guidance Of
Mr.VIRESH K. CHANDURM.Pharm
ASST. PROFESSOR
DEPARTMENT OF PHARMACEUTICS.
SRINIVAS COLLEGE OF PHARMACY, VALACHIL,
MANGALORE – 574143
2012-2014
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE.
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / NAME OF THE CANDIDATE AND ADDRESS / Ms. BHATT HEER SURENDRADEPT. OF PHARMACEUTICS
SRINIVAS COLLEGE OF PHARMACY,
VALACHIL,
MANGALORE TQ- 574143
2. / NAME OF THE INSTITUTION / SRINIVAS COLLEGE OF PHARMACY,
VALACHIL,
POST FARENGIPETE,
MANGALORE TQ- 574143
3. / COURSE OF STUDY AND SUBJECT / M.PHARM- PHARMACEUTICS
4. / DATE OF ADMISSION / 25/06/2012
5. / Title of the Topic:
“STUDY OF FORMULATION VARIABLES OF PROMETHAZINE HYDROCHLORIDE LOZENGES”
6. / Brief Resume of the intended work :
6.1 – Need for the study :
Like the trend world wide, India is undergoing rapid urbanization.Population growth and growing economic activities contribute to many fold increase in travel.
The increase level of travelling of people also increases problems related to the health like motion sickness, traveller’s diarrhoea etc. Motion sickness or Kinetosis, a common problem of travellers is a condition in which a disagreement exists between visually perceived movement and the vestibular systems sense of movement.
The key to succesful drug delivery application is based on meeting unmet need or benefit of use of the choosen system, that’s why a technology selection process will be most successful when considering clinical, technical, medical and buisness benefits. Bringing these four factors together, the selected drug delivery system will significantly enhance patient compliance and market acceptance1.
Oral route of drug administration have wide acceptance upto 50-60% of total dosage forms. Solid dosage forms are popular because of ease of administration, accurate dosage, self-medication, pain avoidance and most importantly the patient compliance. The most popular solid dosage forms are being tablets and capsules; one important drawback of this dosage forms for some patients, is the difficulty to swallow. Drinking water plays an important role in the swallowing of oral dosage forms. Difficulty in the swallowing tablet is a common problem of all age groups, especially elderly and paediatrics, because of physiologic changes associated with these group of patients. Many patients feel difficulty in swallowing conventional tablets when water is not available, in the case of motion sickness (kinetosis) and sudden episodes of coughing during the common cold, allergic condition and bronchitis2.
There are many drugs dosage forms like lozenges, tablets, inhalers and syrups, are in markets for the treatment of the same. The “lozenges are flavoured medicated doasage forms intended to be sucked and held in the mouth/pharynx. These preparations are commonly used for the purpose of local effect as well as systemic effect”.
Advantages of the lozenges as dosage forms include increase in bioavailability, reduction in gastric irritation, bypass of first pass metabolism and increase in onset of action. The new design to this area always benefit for the patient, physician and drug industry. There are several dosage formsalike in the market, there is need for more dosage forms which acts effectivelyboth locally as well as systematically3.
The most effective antidopaminergic agent currently approved for motion sickness is Promethazine hydrochloride(PM HCL), a phenothiazine derivative with antihistaminic, anticholinergic, and sedative effect. It is useful for both active and prophylactic treatment of motion sickness1.
Promethazine hydrochloride is a first generation H1 receptor antagoinst used medically as an antihistamine and antiemetic. It is chemically (RS)-dimethyl [1-methyl-2-(phenothiazine -10-yl) ethyl]amine hydrochloride is an effective and well tolerated antiemetic that has been associated with a wide variety of chemotherapy and radiotherapy regimens2.
In the present study attempt is made to prepare lozenges containing Promethazine hydrochloride for the effective management of the motion sickness and to carry out its stability study as per ICH guidelines.
6.2 / Review of literature :
· Purushotham RK, Shivappa NN, Zakaullah S, Heena Z, Arshiya S have formulated candy based clotrimazole paediatric tablet lozenges, the benefits of the study was to increase the bioavailability, reduction in gastric irritation which were prepared by heating and congealing method the formulation showed highest in-vitro dissolution at 95.01% in 7 mins without hydrocolloid when compared to lozenge with methylcellulose and lozenge with NaCMC4.
· Phaechamund T, Tuntarawongsa S have prepared clotrimazole soft lozenges fabricated with melting and mold technique using PEG as a potential matrix component along with different ratios of glycerine, talcum, xanthium gum, xylitol, saccharin sodium, citric acid orange oil5.
· Dharamjit P,Saumya D have formulated paracetamol medicated lozenges for pediatric use using heating and congealing method. Sodium CMC, methylcellulose were used as polymers. From the In-vitro dissolution studies the formulation contaning sodium CMC 75mg showed 70.012% release and methyl cellulose 25mg showed 90.648 % for release of drug in 30 minutes6.
· Nagoba SN, Rao KP, Sameer S, Gujrathi DS, Nagoba BS have formulated ketoconazole pediatric tablet lozenges using HPMC and HEC as polymers. The result of phase IV studies revealed that the drug release in 30 minutes under simulated salivary condition was 81.12% from HPMC based formulation and 72.43% from HEC based formulation in 30 minutes and 95.01% drug release in 7 minutes from formulation containing without hydrocolloid7.
· Purushotham RK, Shivappa NN, Zakaullah S, Arshiya SA, Ashok KC, Anand C etal.,have formulated medicated lollipops of ketoconazole for pediatric oral thrush patients by using heating and congealing method.HPMC and HEC were used as polymers. The results of phase IV studies revealed that the drug release in 30 minutes under simulated salivary conditions was 94.25%from HPMC and 72.14% from HEC based lollipops8.
· Purushotham RK, Ashok KC, Afshanlaheji, Anilkumar KB, Manjunath P, Baburao NCK have formulated anti asthmatic theophylline tablet lozenges by wet granulation process using acacia and maize starch as polymers. The drug release containing acacia gum showed 81.57% release of drug in 30 minutes and maize starch showed 75.20% release of drug in 30 minutes9.
· Rajesh K, Mahalaxmi R, Deepak K have formulated salbutamol sulfate hard candy lozenges by heating and congealing method to investigate the suitability of Isomalt and/or liquid glucose as the sugar substitute.The Hard candy lozenges containing 2730 mg of 70%w/v Isomalt and liquid glucose showed 95.12% release of drug and 3500mg of 85% w/v Isomalt solution alone showed release 96.36% release of drug in 60 minutes10.
· Purushotham RK, Kamamia EK, Timothy M, Zakaullah S,Arshiya SA, Ashok KC et al., have formulated medicated lollipops of paracetamol for paediatric patients by heating and congealing method using HPMC and HEC as a polymer. The result of phase IV studies revealed that the drug release in 30 minutes under simulated salivary condition was 94.25% from HPMC and 72.14% from HEC based lollipops11.
· Shivappa NN,Purushotham RK, Zakullah S have formulated clotrimazole as lozenge tablet by heating and congealing method using methyl cellulose and guar gum as a polymer. The result of phase IV studies revealed that the drug release in 30 minutes under simulated salivary conditions was 97.45% from guar gum based formulation and 91.76% from methyl cellulose based formulation12.
6.3
7.
8. / Objective of the Study
1. To formulate lozenges of Promethazine Hydrochloride for Motion sickness.
2. To study drug excipient interaction using FTIR.
3. To study formulation variables of medicated lozenges.
4. To evaluate formulated medicated lozenges by various standard evaluation parameters.
5. To carry out stability studies as per ICH guidelines.
Materials and methods
Materials:
1. Drug : Promethazine hydrochloride.
2. Ingredients :Methyl cellulose, Sodium carboxy methyl cellulose,
Hydroxy propyl methyl cellulose, Sweetners,
Flavouring agents, colouring agents, etc.
Drug and excipients of analytical grade will be used.
Methods:Formulation of lozenges can be prepared by different methods which are
classified as :
1. Heating and congealing technique
2. Heat molding method
7.1 Source of Data :
a)Journals:
§ International Journal of Chemical Tech Research
§ International Journal of Pharma Professionals Research
§ Journal of Chemical and Pharmaceutical Research
§ Indian Journal of Pharmaceutical Sciences
§ Journal of Global Pharma Technology
§ International Journal of Health Research
§ Research Journal of Pharmaceutical, Biological and Chemical Sciences
§ International Journal of Research Pharmaceutical Sciences
§ European Archives of Paediatric Dentistry
§ International Journal of Pharma sciences and Research
§ Asian Journal of Pharmaceutical and Clinical Research
§ International Journal of Green Pharmaceuticals
§ Drug Invention Today
b) Internet Browsing.
II) Laboratory based studies
7.2 Method of Collection of Data:
1. Formulation of medicated lozenges of Promethazine hydrochloride.
2. Evaluation for :
a) Physico-chemical Evaluation
Ø Hardness6
Ø Weight variation12
Ø Drug Content6
Ø Thickness12
Ø Diameter10
Ø Friability10
Ø Stability studies as per ICH Q1 guidelines9
b) Drug and Excipient Interaction
Ø By FTIR Spectroscopy11.
c) In- vitro Drug Dissolution Studies
Ø USP II Dissolution apparatus4.
7.3 Does the study require any investigations or interventions to be conducted on humans or animals? If so, please describe briefly.
Not Applicable
7.4 Has ethical clearance been obtained from your institution incase of 7.3?
Not Applicable
List of References:
1. Sachin BM, Sadhana RS, Nandakishor VS, Gaurav RA. Formulation and evalutaion of fast dissolving tablet of promethazine HCL with masked bitter taste.Int J Pharm Res and Dev 2009; 7(1):01-18.
2. Sandeep DS, Kavitha K, Mehaboob Y, Mangesh M. Formulation and evaluation of oral fast dissolving tablets of promethazine HCL by sublimation method. Int J Pharm Tech Res 2011; 3(2):660-03.
3. Purushotham RK, Venkateshwarlu P, Shashikala P, Saran SV, Ravindranath A, Ashok KC, et al., Medicated lollipops for the treatment of oral thrush in children. Int J LifeSc Bt Pharm Res 2012; 1(1):102-09.
4. Purushotham RK, Shivappa NN, Zakaullah S, Heena Z, Arshiya S. Studies on candy based clotrimazole pediatric tablet lozenges. J Chem Pharm Res 2010; 2(3):640-06.
5. Phaechamund T, Tuntarawongsa S. Clotrimazole soft lozenges fabricated with melting and mold technique. Res J Pharm Bio Chem Sci 2010; 1(4):579-86.
6. Dharamjit P,Saumya D. Formulation development and optimisation of paracetamol medicated lozenges for pediatric use. Int J Pharm Sci Res 2012; 3(1):138-40.
7. Nagoba SN, Rao KP, Sameer S, Gujrathi DS, Nagoba BS. Studies on candy based ketoconazole pediatric tablet lozenges. Int J Res Ayurveda Pharm 2011; 2(1):239-43.
8. Purushotham RK, Shivappa NN, Zakaullah S, Arshiya SA, Ashok KC, Anand C etal., Mediacted lollipops of ketoconazole for pediatric oral thrush patients. Int J Inst Pharm LifeSc 2011; 1(3):25-33.
9. Purushotham RK, Ashok KC, Afshanlaheji, Anilkumar KB, Manjunath P, Baburao NCK. Formulation and evaluation of anti-asthmatic theophylline tablet lozenges. Int J Pharm Sci 2011; 3(1):125-08.
10. Rajesh K, Mahalaxmi R, Deepak K. Investigating the suitability of isomalt and liquid glucose as sugar substitute in the formulation of salbutamol sulfate hard candy lozenges. J Chem and Pharm Res 2011; 3(4):69-75.
11. Purushotham RK, Kamamia EK, Timothy M, Zakaullah S,Arshiya SA, Ashok KC et al., Mediacted lollipops of paracetamol for pediatric patients. World J Pharm Pharm Sci 2012; 1(3):1226-34.
12. Shivappa NN, Purushotham RK, Zakullah S. Formulation of clotrimazole as lozenge tablet for improved delivery to oral thrush. J Pharm Biomedical Sci 2011; 12(12):01-04.
13. Latha S, Selvamani P, Thirunavukkarasu C, Kadambavadani R. Formulation development and comparison in evaluation of transdermal drug delivery system for anti-emetic therapy. Int J Res in Pharm Biomedical Sci 2011; 2(2):525-08.
14. Peters MC, Tallman JA, Braun TM, Jacobson JJ. Clinical reduction of S.mutans in pre-school children using a novel liquorice root extract lollipop: a pilot study. European archives of Paediatric Dentistry 2010; 11(6):274-08.
9. / SIGNATURE OF CANDIDATE / (HEER BHATT)
10. / REMARKS OF GUIDE / The Candidate is working under my direct supervision in Laboratories of Srinivas College of Pharmacy, Valachil, Mangalore.
11. / 11.1 NAME AND DESIGNATION OF THE GUIDE
11.2 SIGNATURE / Mr. Viresh K. Chandur M. Pharm.
ASST.PROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
SRINIVAS COLLEGE OF PHARMACY,
MANGALORE.
11.3 HEAD OF THE DEPARTMENT
11.4 SIGNATURE / Dr. A. R. SHABARAYA M.Pharm., Ph.D
HOD AND PRINCIPAL,
DEPARTMENT OF PHARMACEUTICS,
SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, MANGALORE-574143.
12. / 12.1 REMARKS OF THE PRINCIPAL
12.2 SIGNATURE / RECOMMENDED AND FORWARDED.
(DR. A. R SHABARAYA)M.Pharm.,Ph.D
PRINCIPAL AND DIRECTOR,
SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, MANGALORE-574143