FORMULATION AND IN-VITRO EVALUATION
OF GASTRO RETENTIVE FLOATING DRUG DELIVERY SYSTEMS OF TRAMADOL HYDROCHLORIDE
M.Pharm. Dissertation Protocol
Submitted to the
Rajiv Gandhi University of Health Sciences, Karnataka.
Bangalore
By
KEERTHI CHANDRA REDDY.P
B.Pharm
Under the Guidance of
Mr. SARFARAZ. Md
M.Pharm
Asst. Professor
Dept. of Pharmaceutics
DEPARTMENT OF PHARMACEUTICS
N.E.T. PHARMACY COLLEGE
RAICHUR
2011
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 / Name of candidate and address (In Block Letters) / KEERTHI CHANDRA REDDY.P. H.NO:14-78/2,BRAHMANWADI ROAD,
KOSGI-509339,
MAHABUB NAGAR , ANDHRA PRADESH.
2 / Name of the Institute / N.E.T. PHARMACY COLLEGE,
RAICHUR.
3 / Course of study and subject: / M.PHARM. PHARMACEUTICS.
4 / Date of admission of course: /
23-09-2010
5 / Title of the topic:
FORMULATION AND IN-VITRO EVALUATION
OF GASTRO RETENTIVE FLOATING DRUG DELIVERY SYSTEMS OF TRAMADOL HYDROCHLORIDE
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
10 / Remarks of the Guide / The proposed work can be carried out in the laboratory
11 / Name and designation of
(In block letters)
11.1 Guide
11.2 Signature / Mr. SARFARAZ. Md
Asst. Professor,
Dept. of Pharmaceutics,
N.E.T. Pharmacy College,
Raichur-584103.
11.3 Co-Guide (if any)
11.4 Signature / ------
------
11.5 Head of Department
11.6 Signature / Dr. H. DODDAYYA
Professor,
Dept. of Pharmaceutics,
N.E.T. Pharmacy College,
Raichur-584103.
12 / 12.1 Remarks of the Chairman and Principal
12.2 Signature / Forwarded for scrutiny
Dr. H. DODDAYYA
Principal,
N.E.T. Pharmacy College,
Raichur-584103.
Enclosure-I
6) Brief resume of the intended work.
6.1) Need for the study:
The aim of any drug delivery system is to afford a therapeutic amount of drug to the proper site in the body to attain promptly, and then maintain the desired drug concentration. In oral drug delivery system not all drugs or therapeutic agents are absorbed uniformly throughout the gastrointestinal tract (GIT). Some drugs are absorbed in a particular portion of GIT. One of the novel approaches in the area of oral sustained release drug delivery is gastro retentive drug delivery system (GRDDS). Drugs those are having a narrow absorption window and having more solubility in gastric region are suitable candidates for GRDDS1. GRDDS prolongs the retention time of dosage forms in the stomach or upper gastrointestinal tract, as to improve solubility, bioavailability and the therapeutic efficacy of the drugs 2. Several techniques have been proposed to increase the gastric residence time of dosage forms such as buoyancy or floating system3,hydrodynamically balanced system4, expanding or swelling system, bio/mucoadhesive system5, sedimentation or high density system, geometry or modified shape system may also use to increase gastric residence time.
Analgesic means a drug that selectively relieves pain by acting in the CNS or on peripheral pain mechanisms, without significantly altering consciousness6. Pain begins at the level of the cells. In response to injury or inflammation, cells release chemical messengers. These chemical messengers alert other specialized cells called Pain Receptors. The Pain Receptors send signals to the brain. The brain interprets the signals, and we perceive pain. Analgesics work by either blocking the signals that go to the brain or by interfering with the brain's interpretation of the signals7.
Tramadol Hydrochloride is a synthetic 4-phenyl-piperidine analogue of codeine. It is a central analgesic with a low affinity for opioid receptors8. It’s mechanism of action is by inhibition of norepinephrine and serotonine reuptake and thus activates mono aminergic spinal inhibition of pain6. Tramadol Hydrochloride has inhibitory actions on the 5-HT2C receptor. Antagonism of 5-HT2C could be partially responsible for Tramadol Hydrochloride's reducing effect on depressive and obsessive-compulsive symptoms in patients with pain and co-morbid neurological illnesses. Tramadol Hydrochloride is having bioavailability of 68% and short plasma half life of about 6 hrs with the dosage regimen 50 to 100 mg every 4 to 6 hrs with a maximum dosage of 400 mg/day9.
The present system of preparing floating drug delivery system is that, it will remain in gastric region for longer duration causing increase in gastric residence time, which may cause improve in bioavailability and reduces drug waste10. Thus in light of these observations, the present study is planned to design and evaluate the gastro retentive floating tablets of Tramadol Hydrochloride with an aim to localize the drug in the stomach where its absorption is maximum and also to control its release thereby overcoming the adverse effects associated with the currently available conventional release dosage forms of the same drug.
Enclosure-II
6.2) Review of literature:
Ø Debajyoti Ray et al. developed floating drug delivery system of Tramadol Hydrochloride (TH) using different grades of HPMC as drug release retarding polymer and sodium bicarbonate as source for carbon dioxide which helps tablets to float. It was observed that formulation F5 containing HPMC K15Mwas better than all formulations. It was predicted that release of TH from the floating drug delivery systems was of diffusion type10.
Ø Mishra B et al. formulated and evaluated matrix tablets of TH prepared by direct compression technique, using polymers like hydroxypropyl methyl cellulose (HPMC), guar gum (GG) and xanthan gum (XG) alone and in combination in different proportions. Optional excipient, sodium carbonate and diluent lactose were also used. Matrix tablets having HMPC prolonged the rate and extent of drug release maximally followed by XG and GG. Increasing percentage of sodium carbonate in core also further prolonged the rate and extent of drug release. Thus, prepared matrix tablets provided more sustained drug release as compared to commercial sustained release tablets of TH11.
Ø Rajasekhar KK et al. developed a sensitive spectrophotometric for the estimation of Tramadol Hydrochloride in bulk as well as capsule dosage forms. Tramadol Hydrochloride obeyed Beer’s law in a concentration range of 10-150 µg/mL exhibiting maximum absorption at 270 nm. This method was extended to capsule dosage forms and there was no interference from any pharmaceutical additive and diluent. The results were validated statistically and recovery studies confirmed the accuracy of the proposed method12.
Ø Deore RK et al. evaluated the effect of concentration of the hydrophobic polymer content and method of preparation on drug release of sustained release tablet of TH. The tablets were prepared by mixing Tramadol Hydrochloride and glyceryl palmitostearate and tablets prepared by melt granulation or by direct compression. It was observed that glyceryl palmitostearate was a suitable matrix-forming agent to sustain the release of a drug and melt granulation was a better technique for formulating the product than direct compression13.
Ø Amit P et al. prepared a floating drug delivery system of famotidine having poor absorption in acidic environment (upper GIT) using direct compression containing gel-forming agent (HPMC K4M) and retardant (Na-CMC) in different ratio and it was found that gas generating agent (NaHCO3) reacts with HCl and liberates CO2 which creates pores in tablet and elevates swelling and maintains buoyancy. It was concluded that polymer swelling was crucial in determining the drug release rate and was also important for flotation14.
Ø Boldhane SP et al. developed gastroretentive dosage forms of Quetiapine Fumarate using the combination of two hydrophilic polymers, sodium alginate and sodium carboxymethyl cellulose. Quetiapine Fumarate floating tablets was evaluated by 32 full factorial design. It was proved that the technique could used as platform technology for development of gastroretentive dosage forms for the drugs having pH dependent solubility. The combination of the sodium alginate and sodium carboxymethyl cellulose in the ratio of 17 :13 in presence of granulating agent, Eudragit L 30D 55 (3%) and gas generating agent, sodium bicarbonate (10%) was suitable to achieve the desired release profile15.
Ø Jadhav KR et al., carried out the development and in-vitro evaluation of an oral floating matrix tablet formulation of diltiazem hydrochloride (DTZ). The results of factorial design indicated that a high level of both Methocel K100M CR(X1) and Compritol 888 ATO (X2) favors the preparation of floating controlled release of DTZ tablets. The linear regression analysis and model fitting showed that all these formulations followed Korsmeyer and Peppas model, which had a higher value of correlation coefficient (r). While tablet hardness had little or no effect on the release kinetics and was found to be a determining factor with regards to the buoyancy of the tablet16.
Enclosure-III
6.3) Objectives of the study:
The present study is planned with the following objectives:
1) To investigate the drug polymer interactions using DSC and FT- IR instruments.
2) To prepare floating tablets of Tramadol Hydrochloride using various polymers, gas generating and buoyancy enhancing agents.
3) To optimize the formulation by altering the formulation and process variables.
4) To characterize the prepared floating tablets for various physicochemical parameters such as weight variation, hardness, friability, drug content, floating duration, buoyancy lag time etc.,
5) To evaluate the tablets for in vitro dissolution studies.
6) To carry out the stability studies for selected formulations as per ICH guidelines
Enclosure-IV
1) Materials and Methods:
7.1) Source of data:
Primary data: This data will be collected by conducting laboratory experiments
and recording the observation.
Secondary data: This will be collected from various journals and textbooks.
Enclosure-V
7.2) Method of collection of data:
The data for the study is planned to collect from the laboratory-based experiments
1. Preformulation studies like identification, solubility, melting point and flow properties of drug and polymers will be done by employing suitable methods. Compatibility of drug with polymers will be carried out by using FTIR and DSC instruments adopting reported methods.
2. Floating tablets of Tramadol Hydrochloride will be prepared by direct compression method using different grades of polymer such as HPMC, polyacrylate polymers, pectin, guar gum, xanthan gum, psyllium, eudragits etc., and sodium bicarbonate, citric acid, tartaric acid as gas forming agents.
3. Evaluation of floating tablets for weight uniformity, hardness, friability, drug content, floating duration and floating lag time by adopting standard methods.
4. In-vitro release studies will be carried out by using dissolution test apparatus USP XXIV or modified flow through cell apparatus and the drug release data will be subjected to various kinetics models.
5. Stability studies will be carried out for selected formulations using stability chamber as per ICH guidelines.
Enclosure- VI
LIST OF REFERENCES
- Hoffman A, Stepensky D, Lavy E, Eyal S, Klausner E and Friedman M. Pharmacokinetics and pharmacodynamic aspects of gastroretentive dosage forms. Int J Pharm 2004; 27: 141-5.
2. Talukder R and Fassihi R. Gastroretentive delivery systems: A mini review. Drug Dev Ind Pharm 2004; 30(10): 1019-28.
- Tanwar Y, Jaimini M and Rana A. Formulation and evaluation of famotidine floating tablets. Current Drug Delivery 2007; 4: 51-55.
- Ali J, Arora S, Ahuja S, Babbar A, Sharma R, Khar R and Baboota S. Formulation and development of hydrodynamically balanced system for metformin: in vitro and in vivo evaluation. Eur J Pharm Biopharm 2007; 67: 196.
- Varshosaz J, Tavakoli N and Roozbahani F. Formulation and in vitro characterization of ciprofloxacin floating and bioadhesive extended release tablets. Drug Deliv 2006 Jul-Aug; 13(4): 277-85.
- Tripati KD. Essentials of medical pharmacology. 6th Ed. New Delhi 2006.
- http://www.pharmaceutical-drug-manufacturers.com/pharmaceutical-drugs/analgesic`s.html
- http://www.ncbi.nlm.nih.gov/pubmed/9190321.
- Gonjari D J, Hosmani A H, Karmarkar A B, Kadam S B, Godage A S, Khade T S. Microspheres of tramadol hydrochloride compressed along with a loading dose: A modified approach for sustaining release. Drug Discov Ther. 2009; 3(4): 176-180.
- Ray D and Prusty AK. Designingandinvitrostudiesofgastricfloating tablets oftramadolhydrochloride. IntJApplPharm2010; 2(4): 1216.
- Mishra B, Bakde BV, Singh PN and Kumar P. Development and in-vitro evaluation of oral sustained release formulation of tramadol hydrochloride. Acta Pharmaceutica Sciencia 2006; 48: 153-166.
- Rajasekhar KK, Shankarananth V, Jyosthna P, Chowdary SPS and Reddy DP. Spectrophotometric method for the estimation of tramadol in bulk and capsule dosage forms. Journal of Pharmacy Research 2011; 4(2): 386-387.
- Deore RK, Kavitha K and Tamizhmani TG. Preparation and evaluation of sustained release matrix tablets of tramadol hydrochloride using glyceryl palmitostearate. Tropical Journal of Pharmaceutical Research 2010; 9 (3): 275-281.
- Amit P, Kumar JS, Harishanker P, Tarkeshwar S and Arpit S. Formulation development and evaluation of famotidine floating tablet. International Journal of Pharmaceutical Sciences Review and Research 2010; 4(3): 224-229.
- Boldhane SP and Kucheka BS. Gastro retentive drug delivery system of quetiapine fumarate: formulation and in-vitro evaluation using 32 full factorial design. Journal of Pharmacy Research 2009; 2(9): 1427-1433.
- Jadhav KR, Gambier MN, Ambade KW, Kurmi SD, Kadam VJ. Development and in-vitro evaluation of an oral floating matrix tablet formulation of diltiazem hydrochloride. AAPS PharmSciTech 2007; 8 (3): 73.
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