DESIGN AND IN VITRO EVALUATION OF A NOVEL SUSTAINED
RELEASE DOUBLE LAYER TABLETS OF LORNOXICAM
M. Pharm Dissertation Protocol Submitted to
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore– 560 041
By
Mr. Muppa Rama Krishna B. Pharm
Under the Guidance of
Mr. Shivanand Kalyanappa M.Pharm
Asst. Professor
Department of Pharmaceutics,
Acharya & B.M. Reddy College of Pharmacy,
Soldevanahalli, Chikkabanavara (Post)
Hesaraghatta Main Road , Bangalore – 560 090.
2010-2011
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE.
ANNEXURE - II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. / Name of the Candidateand Address / Muppa. Rama Krishna
s/o Madhava Rao
Marabbihal post- 583212
Hagari Bommana halli-Tq
Bellary-Dt
Karnataka.
2. /
Name of the Institution
/ ACHARYA & B.M. REDDY COLLEGE OF PHARMACY,Soldevanahalli,
Chikkabanavara Post,
Hesaraghatta Main Road,
Bangalore-560090.
3. / Course of Study and Subject / M. Pharm
(Pharmaceutics)
4. /
Date of Admission
/25-05-2010
5. / Title of the project:-DESIGN AND IN VITRO EVALUATION OF A NOVEL SUSTAINED RELEASE DOUBLE LAYER TABLETS OF LORNOXICAM.
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6.3
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7.1
7.2
7.3
7.4 / BRIEF RESUME OF THE INTENDED WORK:
NEED FOR THE STUDY:
DOUBLE LAYER TABLETS:
Double layer tablets composed of a fast release layer and a sustain release layer, anticipating the rapid drug release that starts in the stomach to rapidly alleviate the symptoms and continuous in the intestine to maintain protracted effect.
Layered tablet concept is utilized to develop controlled and sustained release formulations. such tablet is considered as biphasic delivery system that is designed to release the drug at two different rates and is usually composed of a fast release layer and sustain release layer. conventional sustain release dosage form delay the release of drugs and do not provide the rapid onset of action after oral administration. Hence this layer tablet offer a pharmacokinetic advantage over conventional dosage forms as the drug is released quickly from the fast layer leading to the rapid raise in drug plasma concentration followed by continuation of drug release from the sustain-release layer. This release pattern is required for successful treatment in many therapies, Primarily when maximum relief needs to be achieved as soon as possible and is followed by a sustained released phase to avoid repeated drug administrated.1
ARTHRITIS:
Arthritis can be defined as the inflammation of joints which may lead to the damage of joints. the arthritis can be classified into various types like
1) Rheumatoid arthritis
2) Osteoarthritis
3) Gout
4) Psoriatic arthritis
Rheumatoid arthritis is a autoimmune disorder that causes the immune system to attack the joints where it causes inflammation (arthritis) and destruction. It can also damage some organs such as the lungs and skin. Studies have shown that this type of arthritis is more common in women than in men.
Osteoarthritis also known as Degenerative arthritis or degenerative joint disease is a clinical syndrome in which low grade inflammation results in pain in the joints caused by abnormal; wearing of the cartilage that covers and act as a cushion inside joints and destruction or decrease of
Synovial fluid that lubricates those joints.
The anti arthritis drug formulation is a challenge to the pharmacist in the present world. The present work will be formulate novel sustain release double layer tablets by using NSAID’S. The NSAIDS are the first choice of the drugs used in the treatment of fever, pain and inflammation in the body. The non-selective COX inhibitors have recently been found to be very effective in the treatment specially for arthritis.
E.g. Lornoxicam, Meloxicam, Piroxicam and some other NSAIDs.
Lornoxicam is a non-steroidal anti-inflammatory drug with analgesic property and belongs to the class of Oxicams. Lornoxicam inhibits the synthesis of prostaglandins via inhibition of cyclo-oxygenase enzyme, but does not inhibit 5-lipo-oxygenase. In-vitro the inhibition of cyclo-oxygenase does not result in an increase in leukotriene formation. It has short biological half-life (3 to 4 h) and the bioavailability is 90%. Moreover, site of absorption of lornoxicam is in the intestine. Therefore, the objective of the present work is to develop a novel sustained- release double- layer tablets of Lornoxicam for the better management of the disease and to minimize side effects as well as to improve patient compliance.2
REVIEW OF LITERATURE
· Chitra Kartikini S et al in their work to develop aceclofenac sodium using super disintegrant, sodium starch glycolate for the fast release layer and water immiscible polymers such as Eudragit RL100 for the sustaining layer. FT-IR studies revealed that there was no interaction between the drug and polymers used in the study. The drug release from F5 Formulation was found to zero order kinetics. It was also found linear in Higuchi’s plot which confirms that diffusion is one of the mechanisms of drug release3.
· Niranjan CP et al in their work to develop a bilayer tablet of propranolol hydrochloride using superdisintegrants sodium starch glycolate for the fast release layer and water immiscible polymers such as ethyl cellulose, Eudragit RLPO and Eudragit RSPO for the sustaining layer. FT-IR studies revealed that there was no interaction between the drug and polymers used in the study4.
· Nagaraju R et al worked on Salbutamol and theophylline which are available in conventional dosage forms, administered four times a day, leading to saw tooth kinetics and resulting in ineffective therapy. The combination of these two drugs in a single dosage form will enhance the patient compliance and prolong bronchodilation. Various polymers, such as hydroxylpropylmethylcellulose K4M (HPMC- K4M), hydroxy propyl methylcellulose K100M (HPMC- K100M), xanthan gum, ethyl cellulose and hydroxy propyl methylcellulose phthalate (HPMC-P) were studied. HPMC-P and HPMC- K4M were found to be best in controlling the release5.
· Frequent dosing of the potent anti-androgen, flutamide, is necessary to reach a therapeutic level for the treatment of prostatic carcinoma. In the present study sustained-release matrix tablets of flutamide were prepared by direct compression method using different polymers. Cellulose ethers (HPMC and Na CMC), natural gums (guar and xanthan gums) and compressible Eudragits (RSPO and RLPO) and their combinations were used in different ratios to examine their influence on tablet properties and drug release profile6.
· Ashish. A et al in their work developed bilayer sustained release tablet of Isosorbide- mononitrate, an anti-anginal organic nitrate vasodilator. The tablets were prepared by wet granulation method. Hydrophilic and hydrophobic matrix materials such as hydroxy propyl methylcellulose, and polyox were used, which can release the drug up to 24hrs in predetermined rate. Binder used was PVP K-30.The influence of hydrophilic and hydrophobic polymer and granulation technique was studied7.
· Prasanthi. N. L et al formulated Bi‐layered tablets of propanolol hydrochloride by using xanthan gum, locust bean gum and guar gum with different drug: gum ratios of 1:0.25, 1:0.5 and 1:1 by wet granulation method. Immediate release layer of the tablet was prepared using super disintegrant such as sodium starch glycolate and sustained release layer was prepared by using gums in different drug to gum ratio. The drug content of the formulations was found with in 98.9‐101.7%. The release of propanolol HCl was extended up to 12 h and was dependent upon the concentration of the gum. The release was better sustained with xanthan gum at the concentration of 1:18.
· Satish Kumar et al in their research work established metformin HCL SR 1000 mg and pioglitazone HCL15 mg in the form of bi-layered sustains release matrix tablets. The tablets were prepared using sodium carboxy methyl cellulose (SCMC) and hydroxy propyl methyl cellulose (HPMC K4M and HPMC 15cps) as bio-adhesive polymers and cross carmellose sodium to act as an impermeable backing layer. The present study concluded that bi-layer tablets of Pioglitazone Hcl and Metformin Hcl can be a good way to extend metabolism and to improve the bioavailability of Pioglitazone Hcl and Metformin Hcl9.
· Sonia Pandey et al formulated Carvedilol as a bilayered buccal tablet in order to avoid the first-pass effect and decrease the drug loss using different polymers and excipients. Eight formulations were made using different ratio of carbopol 934P and HPMC K4M.The formulations were tested for in vitro drug release, in vitro bioadhesion, moisture absorption and in vitro drug permeation through porcine buccal mucosa10.
· Batra. V et al worked on Glipizide, poorly water soluble anti diabetic drug. Here, an attempt to increase solubility and dissolution of glipizide by using solid dispersion using solvent evaporation technique of glipizide using poloxamer 188 and poloxamer407 was made. Effect of several variables such as type of carrier used, drug: carrier ratios were studied11.
· Nidhi. P. Sapkal et al worked on Fexofenadine, a selective histamine H1 receptor antagonist. Solid inclusion complexes of Fexofenadine and beta cyclodextrin were prepared at the molar ratios 1:1 and 1:2 respectively by kneading and co-precipitation methods to improve solubility. Characterization of the complexes was performed using IR spectroscopy, X-ray diffractometry, and in vitro dissolution studies. Phase solubility studies indicated that Fexofenadine forms a stable complex with β-cyclodextrin 12.
· Shrikant P et al worked on Pioglitazone HCL, an antidiabetic drug with poor aqueous solubility. Inclusion complexes of Pioglitazone HCL were prepared with β-cyclodextrin using various methods (physical mixing, kneading and co-precipitation). The main aim of the present invention is to study the effect of the method of preparation on the dissolution profiles of pioglitazoneHCL-β-cyclodextrin inclusion complexes. The method of complexation of pioglitazoneHCL in β-cyclodextrin increased the dissolution rate of the drug in the following order: co-precipitation > kneading > physical mixture > drug13.
OBJECTIVE OF THE STUDY:-
· Characterization of drug, polymers and excipients for the intended drug delivery system.
· To carry out drug polymer compatibility studies.
· To formulate sustained release double layered tablets of lornoxicam which will contain an immediate and a sustained release.
· To minimize the frequency of administration.
· To improve patient compliance.
· To improve therapeutic efficacy.
MATERIALS AND METHODS:
SOURCE OF DATA:-
1) Review of literature from:
a. Journals such as
· Indian Journal of Pharmaceutical Sciences
· Acta Pharma
· American and Eurasian Journal of Scientific Research
· International Journal of Pharmaceutics
· International Journal of Chem Tech and Research
· International Journal of Pharmaceutical Research
· Iranian Journal of Pharmaceutical Research
· International Journal of Pharma and bio sciences
· Asian Journal of Pharmaceutical and Clinical Research
· Science direct
b. World Wide Web
c. J-Gate@Helinet
Method of collection of data:-
1. To carry out preformulation studies
a) Drug-polymer interaction studies using FTIR and DSC.
b) Micromeritic properties:
· Angle of repose
· Bulk density
· Percentage compressibility
2. Preparation of double layer sustained release tablet by direct compression /wet granulation technique.
3. Characterization of fast dissolving tablets by following parameters
a) Physicochemical properties:
· General appearance
· Diameter and thickness
· Hardness and friability
· Weight variation
· Content uniformity
b) In-vitro dissolution studies
4. To carry out stability studies on the most satisfactory formulation as per ICH guidelines at
30 ± 2°C (65 ± 5 %RH) and 40 ± 2°C (75 ± 5 %RH).
DOSE THE STUDY REQIRE ANY INVESTIGATION OR INVESTIGATION TO BE CONDUCTED ON PATEINT OR OTHER HUMAN OR ANIMALS?
“NO”
HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3?
“NOT APPLICABLE”
8 / REFERENCES:
1. Lachman L, Lieberman. A, Kanig. J. The theory and practice of industrial pharmacy. 3rd ed. Mumbai: Varghese publishing house 1990.p.430-1.
2. Tripati KD. Essentials of medical pharmacology. 4th ed. New Delhi: Jaypee brothers medical publishers (p) Ltd; 2001.p.462-3.
3. Chitra Kartikini. S, Jayaprakash. S, Abirami. A, Mohamad Halite. S. Design and formulation of Aceclofenac Sodium bi-layer sustain release tablets. Int J Chem Tech Res 2009; 1(4):1381-5.
4. Patra C.N, Singh S.P, Devi M.V. Design and evaluation of sustained release bi-layer tablets of Propranolol hydrochloride Acta Pharm 2007; 57:479-89.
5. Nagaraju. R, Rajesh kaza. Formulation and evaluation of bi-layer sustain release tablets of salbutamol and theophylline. Int J Pharm Sci and Nanotech 2009; 2(3):638-46.
6. Emami J, Tajeddin M, and Ahmadi F. Preparation and In Vitro Evaluation of Sustained-Release Matrix Tablets of Flutamide Using Synthetic and Naturally Occurring Polymers. Iranian J Pharma Res 2008; 7(4):247-57
7. Ashish. A, Jadhav V. M. Formulation and development of a bi-layer sustain released tablets of isosorbide mononitrite. Int J Pharma and Biosciences 2010; 1(4):305-13.
8. Prasanthi. N.L, Manikiran SS, Rama Rao N. Formulation and evaluation of bi-layered tablets of propranolol HCL by using natural gums. Asian J Pharm Cl Res 2010; 3(4):104-5.
9. Kumar S, Harani A. Formulation and evaluation of bi-layered sustain release matrix tablets of metformin HCL SR and pioglitazone. American-Eurasian J Sci Res 2010; (3):176-82.
10. Pandey S, Gupta A, Singh J. Formulation and In vitro evaluation of bi-layered tablets of carvedilol. Indian J Pharma Edu Res 2010; 44 (3).
11. Batra V, Shirolkar V. S, Kasture P.V. Solubility and dissolution enhancement of glipizide by solid dispersion technique. Indian J Pharma Edu Res 2008; 42(4):373-8.
12. Nidhi P, Sapkal, Vaishali, Bharti D, Daud A. S. Study of the complexation behavior of fexofenadine with β-cyclodextrin. Indian J Pharm Sci 2010; 72(3):318-23.
13. Shrikant P, Dhanyakumar D, Rohit R. Effect of method of preparation of pioglitazone HCL-β-Cyclodextrin inclusion complexes. Asian J Pharm 2010 Apr-June; 168-72.
9 / Signature of the candidate:
10 / Remarks of the Guide:
11 / Name and Designation of:
11.1 / Institutional Guide: / Mr. Shivanand Kalyanappa M.Pharm.
Asst.Professor
Dept. of Pharmaceutics.
11.2 / Signature:
11.3 / Co-Guide: / Gururaj S. Kulakarni M.Pharm.
Lecturer
Dept. of Pharmaceutics.
11.4 / Signature:
11.5 / Head of the Department: / Dr. KALYANI PRAKASAM M.Pharm Ph.D
Professor and HOD
Dept. of Pharmaceutics.
11.6 / Signature
12 / 12.1 / Remarks of the Principal
12.2 / Signature /
Dr. Goli Divakar
Principal
Acharya & B.M. Reddy College of Pharmacy.11