Download design and evaluation of medicated antiemetic lozenges

DESIGN AND EVALUATION OF MEDICATED
ANTIEMETIC LOZENGES
M.PHARM DISSERTATION PROTOCOL
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BENGALURU, KARNATAKA.
BY
ARUNESH KUMAR
Under the guidance of
Mr. BASAWARAJ BENDEGUMBLE
M. Pharm, (Ph.D)
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY
H.K.E.S’s MATOSHREE TARADEVI RAMPURE INSTITUTE OF
PHARMACEUTICAL SCIENCES, SEDAM ROAD
GULBARGA – 585105
2013-2014
0
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA
BENGALURU
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1.
Name of the candidate
(In block letters)
Permanent address
2.
Name of the institution
3.
Course of study and subjects
4.
Date of admission to the course
5.
Title of the topic
6.
Brief resume of the intended work
6.1
ARUNESH KUMAR
S/O ARUN KUMAR SINGH
H. NO. 146, RAM NAGAR COLONY,
BARKHERWA, SITAPUR ROAD, LAKHIMPUR
(KHERI) 262701 UTTAR PRADESH
H.K.E.S’s MTRIPS, SEDAM ROAD
GULBARGA – 585105
M.PHARM
(PHARMACEUTICAL TECHNOLOGY)
30-07-2013
“DESIGN AND EVALUATION OF MEDICATED
ANTIEMETIC LOZENGES”
Need for the study1,2:
Like the trend worldwide, India is undergoing rapid urbanization. Several fold
increase in travel is due to population growth and increasing economic activities and
also increases problems related to the health like motion sickness, traveller’s diarrhea
vomiting etc. The key to successful drug delivery system is based on meeting unmet
necessity or benefit of use of the selected system, that’s why a technology selection
process will be most successful when considering clinical and medical benefits.
Bringing these factors together, the selected drug delivery system will significantly
enhance patient compliance and market acceptance.
Oral route of drug administration has been widely acceptance up to 50-60% of
total dosage forms. Solid dosage forms provide ease of administration, accurate
1
dosage, self-medication, pain avoidance and most importantly the patient compliance.
The popular solid dosage forms are being tablets and capsules; one important
drawback of this dosage forms for some patients, is the difficulty to swallow is a
common problem of all age groups, especially elderly and Paediatrics, because of
physiologic changes associated with this group of patients.
There are many dosage forms like lozenges, tablets, inhalers and syrups, are in
markets for the treatment of the same. The “lozenges are flavored medicated dosage
forms intended to be sucked and held in the mouth/pharynx. These preparations are
used for local effect as well as systemic effect”1.
Advantages of the lozenges as dosage forms include bypass of first pass
metabolism, increase in bioavailability, reducing gastric irritation, and improves onset
of action. The new design to this area always benefits for the patient, physician and
drug industry2.
In the present study attempt will be made to prepare lozenges containing antiemetic drugs for the effective management of the vomiting during travelling and to
carry out its stability study as per ICH guidelines. More amount of the drug will be
absorbed from the buccal cavity and less will be swallowed and lost in GI tract.
Lozenges can be given to children’s or elderly patients improve patient compliance.
6.2
Review of Literature:
Purushotham RK et al, (2010). Have Formulated paediatric lozenges of
clotrimazole to provide slow release medicament for the treatment of oral thrush in
paediatric patients. The benefits of these prepared lozenges are increased
bioavailability, reduction in gastric irritation by passing first pass metabolism. The
lozenges were prepared by heating and congealing method using sucrose as base. All
the formulations prepared were subjected to various physico-chemical parameters. Invitro drug dissolution studies showed 86.08% for F1 and 79.80% for F2 release of drug
in 30 minutes, 95.01% in 7 minutes from F0 formulation. The tablet lozenges can
provide an attractive substitute formulation in the treatment of oral thrush in pediatric
patients3.
2
Rajesh k et al, (2011). Have prepared hard candy lozenges of Salbutamol
sulphate for paediatric, geriatric and Dysphagic patients and investigated the suitability
of Isomalt and liquid glucose as the sugar substitute. Accelerated stability study
conducted as per ICH guidelines (zone IV) at 45°C and 75% relative humidity over a
period of seven weeks found that there wasn’t any substantial interaction between the
drugs, flavour and colour and the prepared formulations were stable4.
Rachana M et al, (2013). Reviewed lozenges a unit dosage form of medicament
meant to be dissolved in mouth or pharynx. Lozenges currently available in market are
of four types: Caramel based soft lozenges, hard candy lozenges and compressed tablet
lozenges. The present review covers more or less all aspects associated with lozenge. It
includes various researches performed till date, formulation and evaluation parameters
adopted for the dosage form. Furthermore, it throws light on the applications of
lozenges5.
Harri H et al, (2011). Have designed zinc medicated lozenges for paediatric
using a number of controlled trials have examined the effect of zinc lozenges on the
common cold but the findings have diverged. Three trials used zinc acetate in daily
doses of over 75 mg, the pooled result indicating a 42% reduction in the duration of
colds (95% CI: 35% to 48%). Five trials used zinc salts other than acetate in daily doses
of over 75 mg, the pooled result indicating a 20% reduction in the duration of colds
(95% CI: 12% to 28%).. The effects of zinc lozenges should be further studied to
determine the finest lozenge compositions and treatment strategies6.
Purushotham RK et al, (2013). Have designed medicated lozenges for
paediatrics of Montelukast sodium for the treatment of asthma in paediatric patients.
The present investigation prepared and evaluated lozenges of Montelukast sodium
using hydroxy propyl methyl cellulose as polymer different concentrations to increase
retention time. In-vitro drug dissolution studies showed 69.24% for F2, 64.01% for F3
release of drug in 30 min, 97.31% in 10 minutes from F1 formulation. IR spectroscopic
studies indicated that there were no drug-excipient interactions. The prepared lozenges
of Montelukast sodium could stay in the mouth for a longer period of time, which
indicates a potential use of these lozenges for treating asthma7.
3
Dharamjit P et al, (2012). Have formulated paracetamol medicated lozenges for
paediatric use using heating and congealing method. Sodium CMC, methylcellulose
were used as polymers. From the In-vitro dissolution studies the formulation containing
sodium CMC 75mg showed 70.012% release and methyl cellulose 25mg showed
90.648 % for release of drug in 30 minutes8.
Vegad RM et al, (2013). Prepared lozenges by direct compression procedure
using different concentration of xylisorb and Avicel 102. Compatibility studies of drug
and polymer were performed by FTIR spectroscopy. FTIR spectroscopy revealed that
there was no possible interaction between drug and polymers. Crushing strength of
troches was determined and was found to be in the range of 50-80 Newton/cm2.
Lozenges (troches) of Cetylpyridinium Chloride and Benzocaine were prepared by
direct compression9.
Chui Chong et al, (2009). Formulated lozenge formulation of ketamine for
use in patients with neuropathic pain, and to investigate its storage stability and
bioavailability after oral or sublingual administration. A lozenge containing 25 mg of
ketamine was formulated and manufactured in a hospital pharmacy setting. Ketamine
and its metabolite norketamine in plasma were measured by HPLC. Oral and sublingual
bio-availabilities were 24% (17–27%) and 24% (19–49%), respective. The mean
norketamine/ketamine area under the plasma concentration-time curve from baseline to
8 hours ratios were5 and 2.1 after oral or sublingual administration, respectively10.
Purushotham et al, (2011). Designed compressed tablet lozenges of
anhydrous theophylline to provide slow release medicament for the treatment of
bronchial asthma associated with wheezing, breathlessness, chest tightness and
coughing. The lozenges were prepared using sucrose as base and gelatin dispersion as
binder. The prepared formulations have a hardness of 9-10 Kg/cm², not gritty, mouth
feel freshness taste. Stability studies were carried out at 30ºC & 40°C for a period of six
months. Some selected formulations were tested for drug excipient interactions
subjecting to IR Spectral analysis. In-vitro drug dissolution studies showed 81.57% for
F1 and 75.20% for F2 release of drug in 30 minutes. The compressed tablet lozenges
can provide an attractive alternative formulation in the alleviation of bronchial asthma
and other respiratory disorders11.
4
Phaechamud T et al, (2010). Have studied clotrimazole soft lozenges
fabricated with melting and mold technique. The soft lozenges prepared by mold
technique have potential to improve the solubility of clotrimazole since it was dispersed
in PEG system12.
Damian W et al, (2010). Have studied in-vitro antimicrobial evaluation of
lozenges containing extract of garlic and ginger. The formulated product showed
inhibitory activity against non-resistant C. albicans infection. Garlic-ginger has been
successfully formulated as a lozenge for purpose of taste masking, crude drug release
and consequent antimicrobial activity13.
Purushotham RK et al, (2012). 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 lollipops14.
6.3
Objectives of the study:
 To fabricate medicated tablet lozenges for antiemetic treatment.
 To formulate an alternative dosage form for children/ elderly patients.
 To improve patient compliance and acceptance.
 To achieve maximum drug efficacy.
 To help the manufacturers to take up for future studies and introduce into the
market such formulations.
 To design a dosage form that is more effective and acceptable than the existing
marketed formulations.
7.
7.1
Materials and Methods:
Source of Data:
 Internet, www.rguhs.ac.in.
 M.R.Medical college library, Gulbarga.
 International pharmaceutical abstract.
 H.K.E.S’s college of pharmacy library, Gulbarga.
5
7.2
Methods of collection of data
Materials and Methods:
It is planned to use sucrose, citric acid, calcium carbonate, sodium bicarbonate, HPMC,
HEC, and all other chemicals will be used of analytical grade. In the present price of
research work Fluconazole, Nystatin etc. chosen as model drug.
PHASE-1:Preparation of medicated tablet lozenges:
Syrupy base will be prepared following established method by dissolving the sugar in
purified water and heating up to 140O F (113O C) for a period of 1hr. Other excipents
like acidulents will be added in geometrical ratio to the syrupy base on continues
stirring. By dispersing in glycerine and warming up to 60O separately. Specially
designed 4gms capacity stainless steel molds are planned to use during formulation of
lozenges.
PHASE-II: Characterization of prepared tablet lozenges:
The prepared tablet lozenges will be subjected to various physico-chemical parameters
like hardness, size, shape, weight variation, and drug content estimation etc.. to check
the drug excipients interactions if any. The prepared formulation will be subjected for
IR, TLC, DSC, DTA studies.
PHASE-III: In-vitro Drug release studies:
All the formulations prepared will be subjected for in vitro drug release using electro
lab six-basket tablet systematically using USP XXIII dissolution apparatus in PH 6.7
MEDIA AT 37OC.
PHASE-IV
The entire prepared tablet Lozenges will be subjected for stability studies for a period
of three months. The drug content estimation will be carried out on the sample taken at
various time intervals for 15 days.
6
7.3
Does the study require any investigation or invervention to be conducted on
patients or other humans or animals? If so please describe briefly
---------------------Not in the study---------------------------------
7.4
Has ethical clearance have been obtained from your institution in case of 7.4?
--------------------Not applicable-----------------------------------
8
List of References
1. William R. Pfister and Tapash K. Ghosh. Drug Delivery to the Oral Cavity. CRC Press
by Taylor & Francis Group, 2005.
2. Purushotham RK, Venkateshwarlu P, Shashikala P, Saran SV, Ravindranath A, Ashok
KC. Medicated lollipops for the treatment of oral thrush in children. Int J LifeSc Bt
Pharm Res, 2012; 1(1):102-09
3. Purushotham RK, Shivappa N, Nagoba, Zakaullah, Heena Z and Arshiya S. Studies on
candy based Clotrimazole paediatric tablet lozenges. J. Chem. Pharm. Res, 2010; 2(3):
640-46.
4. Rajeshi 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. Pharm. Res, 2011; 3(4): 69-75.
5. Rachana M, Vikas J, Rehana A, Garvita joshi. A review on lozenges. BBB 2013;
1(1):35-43.
6. Harri H. Zinc Lozenges May Shorten the Duration of Colds:A Systematic
Review. The Open Respiratory Medicine Journal, 2011; 5: 51-58.
7. Purushotham Rk, Girish K, Ajay K, P Manjunath. Design of medicated lozenges for
paediatrics. IJRMHS, 2013; 2: 2307-208311.
8. Dharmajit P and Saumya D. Formulation development and optimization of medicated
lozenges for paediatrics use. IJPSR, 2012; 3(1): 138-40.
9. Vegad RM, Jain DA & Panchal. Formulation and development of antiseptic pain-relief
tablet lozenges (troches) for treatment of oral diseases.IJOPILS: 2320 – 0782, 2013;
(I6) : 90-99.
10. Chui Chong, Stephan A. Schug, Madhu Page-Sharp, Barry Jenkins and Kenneth F.
Ilett. Development of a Sublingual/Oral Formulation of Ketamine for Use in
Neuropathic Pain. Clin Drug Invest, 2009; 29 (5): 317-24.
11. Purushotham RK, Ashok K, Manjunath P, Baburao N. Formulation and Evaluation of
Anti-Asthmatic theophylline Tablet Lozenges. IJPS, 2011; 3(1): 125-28.
12. Phaechamud T, Tuntarawongsa S. Clotrimazole soft lozenges fabricated with melting
and mold technique. Res J Pharm Bio Chem Sci, 2010; 1(4): 579-86.
13. Damian CO, Charles OE, Festus BCO, Nworu CS, Oleghe PO, Ejogha PW. In- vitro
antimicrobial evaluation of lozenges containing extract of garlic and ginger. Int J
Health Res, 2010; 3(2): 105-10.
14. Purushotham RK, Kamamia EK, Timothy M, Zakaullah S,Arshiya SA, Ashok KC.
Mediacted lollipops of paracetamol for pediatric patients. World J Pharm Pharm Sci,
2012; 1(3): 1226-34.
7
9.
10.
Signature of candidate
Remarks of Guide
ARUNESH KUMAR
College has all the facilities to work .Hence this work
is practicable.
11. Name and designation of
(in block letters)
11.1 Guide
BASAWARAJ BENDEGUMBLE
M. Pharm., (Ph.D.)
LECTURER
DEPT.OF PHARMCEUTICAL TECHNOLOGY
H.K.E.S’s MATOSHREE TARADEVI RAMPURE
INSTITUTE OF PHARMACEUTICAL SCIENCES
GULBARGA – 585105
11.2 Signature
11.3 Co-guide
Dr. M.V.RAMPURE
M.Pharm., Ph.D
Asst.Professor
DEPT.OF PHARMCEUTICAL TECHNOLOGY
H.K.E.S’s MATOSHREE TARADEVI RAMPURE
INSTITUTE OF PHARMACEUTICAL SCIENCES
GULBARGA – 585105
11.4 Signature
11.5 Head of the Department
Dr. K PURUSHOTHAM RAO
M.Pharm., Ph.D
Professor
DEPT.OF PHARMCEUTICAL TECHNOLOGY
H.K.E.S’s MATOSHREE TARADEVI RAMPURE
INSTITUTE OF PHARMACEUTICAL SCIENCES
GULBARGA – 585105
11.6 Signature
12
12.1 Remarks of Chairman
and Principal
12.2 Signature
8