“FORMULATION ANDIN-VITROEVALUATIONOF TRAMADOL HYDROCHLORIDEFLOATING TABLETS”
M. Pharm. Dissertation Protocol Submitted to
Rajiv Gandhi University of Health Sciences, Bangalore
Karnataka
By
Mr. PALLA NARENDRA B.Pharm
Under the Guidance of
Mr. RAJASHEKAR VALLURU
Assistant Professor
DEPARTMENT OF PHARMACEUTICS
EAST WEST COLLEGE OF PHARMACY
BANGALORE – 560091
2011-2013
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 / Name of candidate and address (In Block Letters) / PALLA NARENDRA,D.NO:3-140, ALLURIVARIPALLEM,NARASARAOPET, GUNTUR (DT), ANDHRAPRADESH.
2 / Name of the Institute / EAST WEST COLLEGE OF PHARMACY, BANGALORE -560 091.
3 / Course of study and subject: / M.PHARM. PHARMACEUTICS.
4 / Date of admission of course: / 21-7-2011
5 / Title of the topic:
“FORMULATION ANDIN-VITRO EVALUATION OF TRAMADOL HYDROCHLORIDE FLOATING TABLETS”
6 / Brief Resume of this intended work:
6.1 Need for the study Enclosure-I
6.2 Review of Literature Enclosure-II
6.3 Objectives of study Enclosure-III
7 / Materials and Methods:
7.1 Source of data Enclosure-IV
7.2 Method of collection of data (Including sampling procedure, if any)
Enclosure-V
7.3 Does the study require any investigation or interventions to be conducted on patients of humans or animals? If so, please describe briefly.
------NO------
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
------NOT APPLICABLE------
8 / List of References Enclosure-VI
9 / Signature of the candidate / (PALLA NARENDRA)
10 / Remarks of the Guide / The proposed research work will be carried out in the Academic Laboratory and is recommended for approval and registration
11 / Name and designation of (in block letters)
11.1 Guide
11.2 Signature / Mr. RAJASHEKAR VALLURU
ASSISTANT PROFESSOR,
DEPT. OF PHARMACEUTICS,
EAST WEST COLLEGE OF PHARMACY,
BANGALORE-560 091.
11.3 Co-Guide (if any)
11.4 Signature / ------
------
11.5 Head of Department
11.6 Signature /
Dr. JAGADEESH G.HIREMATH
PROFESSOR& DIRECTOR
12 / 12.1 Remarks of the Chairman/Principal
12.2 Signature / The proposed research work will be carried out in the Academic Laboratory and is recommended for approval and registration
Prof. K.A. SRIDHAR
PRINCIPAL,
EAST WEST COLLEGE OF PHARMACY,
BANGALORE - 560 091.
ENCLOSURE-I
6) Brief resume of the intended work:
6.1) Need for the study:
Oral route of administration gets the highest priority for the delivery of drug as well as better patient compliance. Prolonged and predictable drug delivery in the gastro intestinal(GI) tract is to control the gastric residence time (GRT), i.e. gastro retentive dosage form (GRDF). Gastric residence time is the time until which the dosage form remains in the gastric fluid for absorption.If there is an increase in GRT, then there may be an increase in the bioavailability of the drug and if there is a decrease in GRT, then there may be decrease in bioavailability of the drug.
The floating drug delivery systems are designed on the basis of delayed gastric emptying and buoyancy principles appear to be an effective and rational approach to the modulation of controlled oral drug delivery. These systems were useful for those drugs that act locally in the proximal part of gastrointestinal tract, or are poorly absorbed in the intestine. These dosage forms have a density lower than that of the gastric fluid. After oral administration, they can remain in the stomach and deliver drugs in a sustained release manner.1
Tramadol hydrochloride is a centrally acting opioid analgesic its chemical name is (1R,2R)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexan-1-ol, molecular formula is C16H25NO2,its molecular weight is 263.37 and structurally related to codeine and morphine used in the treatment of moderate to severe pain in diverse conditions. Combined with low dependence/abuse potential, it has proven to be of significant advantage over other agents, especially in the elderly. Routes other than oral, like intravenous, which are used to administer tramadol, are used in acute conditions like postoperative neuralgia or situations when the patient is hospitalized. Unlike insulin, tramadol must be injected under the supervision of a physician only.2Tramadol is a centrally acting analgesic relieves pain by opioid as well as additional mechanisms, its affinity for µ opioids receptor is low, while that for k and δis very low.Unlike other opioids, it inhibits re uptake of NA and 5-HT, and thus activates monoamenergic spinal inhibition of pain. Its analgesic action is only partially reversed by the opioid antagonist naloxone. A specific absorption window limited only to the upper part of the small intestine coupled with high frequency of drug administration (4–6 hourly), dose (100 mg) and short biological half‐life (6–8 h) rationally call for the development of its gastro retentive CR product.3Various approaches including floating systems, bioadhesive systems, swelling and expanding systems and high density systems have been successfully employed to improve the gastric residence time of drug delivery system.4
The current study is aimed to prepare novel floating tablets oftramadol hydrochloride and to carry out the in-vitro evalution.
ENCLOSURE-II
6.2) Review of literature:
Literature review for understanding the study was done by referring to various national and international journals, published articles in various official standard books and referring to various websites.
Liandonget al.,have developed the dextromethorphan hydrobromide sustained-release (DMB-SR) tablets using floating technique to prolong the gastric residence time and compared their pharmacokinetic behavior with conventional sustained release tablets. DMB-SR floating tablets were prepared employing hydroxypropyl methylcellulose (HPMC) as hydrophilic gel material, sodium bicarbonate as gas-generating agent and hexadecanol as floating assistant agent. An orthogonal experiment design method was used to select the optimized formulation. Their prepared floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, floating characteristics, in-vitro release and in-vivo bioavailability. 1
Shaikhet al., have developed the directly compressible floating‐bioadhesive tablets of tramadol, using varying amounts Carbopol 971P (CP) and hydroxypropylmethylcellulose (HPMC), along with other requisite excipients. In-vitro drug release profile, floating characteristics and ex vivo bio adhesivestrength using texture analyzer were determined and systematically optimized using a 32 central composite design (CCD). Their studies indicated successful formulation of gastroretentive compressed matrices with excellent controlled release, mucoadhesion and hydrodynamic balance was reported.5
Rayet al.,have investigated onfloating deliverysystem of tramadolhydrochloride,they prepared using different grades of HPMC as drug release retarding polymer and sodium bicarbonate as source for carbon dioxidewhich helps tablets to float. From their FTIR studies no interactions were found between TH and polymers. The flow properties of the granules were studied by them and formulation F5 was found to have comparatively good compressibility index andhausner ratio than other formulations. From their swelling study of the formulations, formulation F5 was found to have good swelling properties (220%)drug release kinetic study revealed thatHiguchimodelwas found to be best fit. So it could be predicted that release of TH from the floating drug delivery formulations were of diffusion type.6
Ajay etal.,have formulated floating tablets of ciprofloxacin HCl with HPMC and carbomer in different proportion (4% to 12%) by direct compression techniques using polymers lactose, magnesium streate, talc with sodium bicarbonate. All the formulations were found to complies with the official tests like precompression parameter like angle of repose and post compression parameters like shape, tablet dimensions, hardness, friability test, weight variation test, floating test, content uniformity and in-vitro dissolution study. In-vitro release studies were carried out using USP XXII dissolution test apparatus. The mean percentage of ciprofloxacin released at various time intervals was calculated and plotted against time. The mechanism of drug release with all the formulations was dominantly diffusion and followed zero order kinetics. They were observed that the integrity of the drug is not affected by formulation procedure. Their results revealed that the drug polymer ratio showed greater drug release than other formulations.7
Kavitaet al .,have prepared a floating drug delivery system of ranitidine hydrochloride(RHCL) in order to increase the gastric residence time (GRT) and comparison of natural and synthetic polymer for bettersustained effect. The tablets were prepared by direct compressiontechnique. The drug: polymer interaction was determined by IRspectroscopic method. The pre and post compression studies were performed by using IP standard formula and procedure.Drug release from the floating drug delivery system was studied using USP ІІ. Their formulation with guar gum and xanthum gum showedbetter sustained release effect than HPMC different grade.8
Satapathy et al ., have investigated on anti-GERD activity of gastro-retentive drug delivery system of itopride hydrochloride wherein they have formulated floating hydrogel-based microspheres employing calcium carbonate (CaCO3) as a gas forming agent dispersed in alginate matrix. In-vitro characterizations such as drug content, particle size, and drug release were carried out. Their results demonstrated that prepared microspheres were spherical in shape with smooth surface, had good loading efficiency and excellent buoyancy. Their formulated gastro retentive dosage form of itopride demonstrated significant antacid, anti-ulcer, and anti-GERD activity after 12h in comparison with the conventional dosage form.9
Patil et al., have studied the controlled release dosage forms by formulating and evaluating intra-gastric hydrodynamic balanced system of itopride hydrochlorideusing gas generating agent (sodium bicarbonate), hydrophilic polymer (different grades of hydroxy propyl methyl cellulose) and drug release retarding agent (Eudragit RSPO) with an objective to control the drug release and restrict the region of drug release to stomach. They have prepared tablets by direct compression method and the compression force of the machine was adjusted to obtain the hardness of 4 kg/cm2 and 6 kg/cm2 for different batches. They confirmed that stability of the drug in the formulations by FTIR studies. All their formulations showed good buoyancy time (8-12 h). Swelling study indicated that swelling of the tablet increased with respective to time and directly proportional to the viscosity of the polymer. In-vitro drug release studies of the tablets indicated controlled release for itopride hydrochloride.10
ENCLOSURE-III
6.3) Objective of the study:
The present study is planned with the following objectives:
To prepare tablets containing tramadol hydrochloride by direct compression technique or any suitable method.
Pre-compression is carried out depending up on the method of preparation.
To investigate the post compression parameters of the developed formulations.
In-vitro characterization of the developed floating tablets.
To determine the in-vitro drug release studies.
ENCLOSURE-IV
7) Materials and Methods:
Materials:
Drug : Tramadol hydrochloride.
Polymers and excipients : HPMC K-15, HPMC K-100M, Cabopol-934, PVP K-30, Talc, magnesium stearate, sodium bicarbonate and citric acid ,other appropriate polymersand excipients which will be used for the preparation of formulations.
Methods:
Tramadol hydrochloride tablets will be prepared by direct compression technique/wet granulation technique where varying concentrations of different polymers.
7.1) Source of data:
This data is obtained from the formulated floating drug delivery tablets of various drugs.
Data is collected from:
Internet.
RGUHS Library.
Research publications.
International and Indian journals.
Textbooks and reference books.
ENCLOSURE-V
7.2 Method of sampling, collection and evaluation of data: (Including sampling
procedure, if any)
Tablets will be prepared by direct compression or other suitable methods.
Preformulation studies including polymer selection,excipents selection and compatibility and development of formulation of floating tablets.
Determination of floating time.
Evaluation
Pre compression parameters are carried out if applicable.
Post compression parameters include the study of weight variation, hardness, thickness, friability time and dissolution.
Determination of hardness by Monsanto hardness tester.
Determination of friability by Roche Fribilator.
Estimation of drug content in developed sample.
In-vitro drug release studies of the formulationsby UV-Visible spectrophotometry.
ENCLOSURE- VI
8) List of references:
- Hu L, Li L, Yang X,Liu W, Yang J, Jia Yet al.,Floating matrix dosage form for dextromethorphan hydrobromide based on gas forming technique: in-vitro and in-vivo evaluation in healthy volunteers.Eur J Pharm Sci 2011;42:99-105.
- Raval SB, Prajapati R, Shah NV, Ghelani TK, Seth AK, Saini V et al., Formulation and evaluation of tramadol hydrochloride mouth dissolving tablet. J Pharm Tech2010;2(11):17-22.
- Tripathi KD. Essentials of medical pharmacology. 6th ed. Jaypee Brothers Medical Publications. New Delhi :( IND) 2008; 460-62.
- Singh B, Rani A, Babita, Ahuja N, Kapil R.Formulation optimization of hydrodynamically balanced oral controlled release bioadhesive tablets of tramadol hydrochloride. Sci Pharm 2010;78(2):303-23.
- Shaikh AC, Quazi A, Nazim S, Quazi M, Siraj S, Khan Tet al., Formulation optimization of hydrodynamically balanced oral controlled release bioadhesive tablets of tramadol hydrochloride. Asian J Pharm Clin Res 2011;4:61-70.
- Debajyoti R, Amresh KP. Designing and in-vitro studies of gastric floating tablets of tramadol hydrochloride. Int J Appl Pharm2010;2:12-16.
- Ajay B, Dinesh Kumar P, Pradeep S. Studies on formulation and evaluation of floating tablets of ciprofloxacin Hcl. Int J C Pharmacy2010;01:1-4.
- Kavita K, Sudhir K, Yadav, Tamizhamani T. Formulation and evaluation of floating tablets of RHCL using natural and synthetic polymers. Int J Pharm Tech Res2010;2:1513-19.
- Sathapathy T, Prasana KP, Amit K, Gouthm R. Evaluation of anti-GRED activity of
gastro retentive drug delivery system to itopride hydrochloride. Artif Cell Blood Sub 2007;38(4):200-7.
- Kumar MS, Patil A, Ramakrishna R, Dana SB, Kumar VN. Formulation and evalution of intra-gastric hydrodynamic balanced system of itopride hydrochloride. Res J Pharm Bio Chem Sci 2010;1:137-42.
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