Formulation and Evaluation of Antihypertensive Bilayer Matrix Tablets

FORMULATION AND EVALUATION OF ANTIHYPERTENSIVE BILAYER MATRIX TABLETS

M.PHARM DISSERTATION PROTOCOL

SUBMITTED TO

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES

KARNATAKA

PATEL TARUNKUMAR VITTHALBHAI

I M.PHARM

UNDER THE GUIDANCE

MR.S RAJARAJAN

ASSISTANT PROFESSOR

DEPARTMENT OF PHARMACEUTICS

KARNATAKACOLLEGE OF PHARMACY

BANGALORE-560064

(2010-2011)

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

ANEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1 / Name of the Candidate and Address / PATEL TARUNKUMAR VITTHALBHAI
#33/2, Thirumenahalli
Hegde nagar main road
Bangalore 560064.
PERMANENT ADDRESS
At.-Shyamnagar
Ta.-Dhansura
Dist.-Sabarkantha
Pin-383307
Gujarat
2 / Name of the Institute / KarnatakaCollege of Pharmacy
#33/2, Thirumenahalli
Hegde nagar main road
Bangalore 560064.
3 / Course of the Study & Subject / Master of Pharmacy ( Pharmaceutics )
4 / Date of Admission to the Course / 14th December 2009
5 / Title of Topic
FORMULATION AND EVALUATION OF ANTIHYPERTENSIVE BILAYER MATRIX TABLETS
6 / Brief resume of the intended worktivit
6.1
6.2 / Need for the study
Oral drug delivery is the simplest and easiest route of administrating drugs because of smaller bulk, accurate dosage and easy production. Solid dosage forms have many advantages over other types of oral dosage forms. Up to 40 percent of new chemical entities discovered by the pharmaceutical industry today are poorly soluble or lipophilic compounds. The solubility issues complicating the delivery of these new drugs also affect the delivery of many existing drugs. Poorly water-soluble drugs show unpredictable absorption, since their bioavailability depends upon dissolution in the gastrointestinal tract.
Different types of oral controlled release solid formulationssuch as matrix tablets and capsuleshave beendeveloped to improve treatment and clinical efficiency.Recently multilayer tablets feature more frequently inthe design of oral sustained drug delivery systems. These systems consist of an active matrix core and oneor more barriers applied during tabletting. The barriersdelay the interaction of the core with the dissolutionmedium by reducing the surface available for drugrelease and thus limiting liquid penetration. These formulationsare designed to deliver the drugs at a sustainedand predetermined rate, thus maintaining theirtherapeutically effective concentrations in the systemiccirculation for prolonged periods of time.
Dependingon material characteristics these systems may swell, gel,erode, and finally dissolve in the gastrointestinal tract.The control of overall release is primarily determined bythe composition of each layer. Multilayer systems permitthe production of various tablet structures possessingdifferent release properties that result in a range ofdissolution profiles. Layered tablets show a number ofadvantages and greater flexibility in obtaining differentdrug release profiles such as zero order, bimodal, pulsatile,and delayed release.
Anti-hypertensive has been widely used in the treatment of hypertension and cardiac arrhythmias among the drugs with relatively short plasma half-life, patients are routinely asked to take frequently. The current research is to formulate and evaluate anideal antihypertensive bilayer matrix tablet of sustained release profile by using suitable methods and polymers
Review of Literature
Chinam NPet al1developed design and evaluation of sustained release bilayer tablets of propranolol hydrochloride. The objective of the present research was to develop a bilayer tablet of propranolol hydrochloride using superdisintegrant sodium starch glycolate for the fast release layer and water immiscible polymers such as ethylcellulose, Eudragit RLPO and Eudragit RSPO for the sustaining layer. Statistical analysis (ANOVA) showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05) in the amount of drug released after 12 h from optimized formulations was observed.
Raghavendra NGR et al2developed controlled zero order release Glipizide bilayer matrix tablets using different grade of hydroxy propyl methyl cellulose along with xanthan gum , guar gum and karya gum and were prepared by wet granulation method. The release rate were modulated by varying concentration of different type of rate controlling material and evaluation physical properties and in vitro release study was performed and stability study were carried out and for 6 month indicate glipizide was stable in matrix tablet.
Nagaraju Ret al3developed formulation and evaluation of bilayer sustained release tablets of salbutamol and theophylline. Salbutamol and theophylline 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 dosageform will enhance the patient compliance and prolong bronchodilation.In-vitrodissolution studies were carried out for all the bi-layered tablets developed using USPdissolution apparatus type 2 (paddle). In-vitrodissolution studies were carried out for all the bi-layered tablets developed using USP dissolution apparatus type 2 (paddle).
Bhavesh S et al4 developed bilayer tablet of metoclopramide hydrochloride and Ibuprofen for the effective treatment of migraine. MTH and IB were formulated as immediate release and sustained release layer respectively. The dissolution study of sustained release layer showed that increasing amount of HPMC result in reduced IB layer. MTH increase the absorption of acidic NSAIDS by increasing gastric motility. MTH degrade when prolonged contact with acidic NSAIDS. Bilayer tablet was preventing direct contact of these drug.
Efentaksi M et al5developed multilayer tablets more frequently in the design of oral sustained drug delivery system and improve treatment and clinical efficiency. These systems consists of an active matrix core and one or more barriers applied during tabletting. To examine the release performance of two model drugs, diclofenac sodium and furosemide, from two- and three-layer of drug delivery systems using as carrier hydrophilic swellable polymers, namely, Metolose, Polyox, Xantham gum and an erodible material Gantrez. The difference between the two- and three- layer tablets are small as it appears that two-layer tablets exhibit a slightly higher release and because of its greater erosion Gantrez formulations displayed faster release relative to Xantham gum, as did Metolose formulations compared to Polyox formulations.
Ramesh et al6 established metformin HCL SR 1000 mg and pioglitazone HCL 15 mg in the form of bi-layered sustained release matrix tablets and prepared using sodium carboxymethylcellulose and hydroxypropyl methylcellulose as bio-adhesive polymer and cross carmellose sodium to act as an impermeable backing layer. The formulation gave an immediate release effect followed by sustained release for 8 hrs. The stability studies of formulated product also comply with ICH guidelines.
Sajjan A et al7developed Multi-drug tablets of amlodipine besylate and atenolol were prepared as either mono-layer (mixed matrix) or bi--layer tablets containing each drug in a separate layer by using similar excipients and processing. Each tablet batch was packed in strip and blister packs and kept under accelerated temperature and humidity conditions. Amlodipine content in bi-layer tablets decreased to about 95 and 88% when packed in strips and blisters. The study revealed that the bi-layer tablet formulation was more stable than the mono-layer type. Stability was increased when the tablets were packed in aluminium strips as compared to PVC blisters.
Gohel MC et al8investigated were to achieve immediate release of paracetamol and tailored release of diclofenac sodium from bi-layer tablets and were prepared by using hydroxypropyl methyl cellulose as a matrixing agent. The analysis showed that the friability of paracetamol was distinctly influenced by the formulation variables. The bi-layer tablets shown immediate release of paracetamol and modified release of diclofenac.
Rakesh KD et al9 prepared oral sustained release matrix tablets of a highly water soluble drug, tramadol hydrochloride and to evaluate the effect of concentration of the hydrophobic polymer content and method of preparation on drug release. The tablets were a mixture of both tramadol hydrochloride and glyceryl palmitostearate (GP) prepared by melt granulation or by direct compression. Glyceryl palmitostearate is a suitable matrix-forming agent to sustain the release of a water-soluble drug such as tramadol hydrochloride. Melt granulation was a better technique for formulating the product than direct compression.
Naeem MA et al10 developed bilayer tablet formulations of tramadol HCl (TmH) and acetaminophen (AAP) microparticles Coacervation via temperature change was the encapsulated method used for the preparation of the microparticles, with ethyl cellulose (EC) of medium viscosity as the polymer for extending drug release. The physicochemical compatibility and stability of the tablets were determined by Fourier transform infrared spectroscopy (FTIR), x-ray diffractometry (XRD), differential scanning calorimetry DSC) and thermogravimetric analysis (TGA). Microencapsulated TmH and AAP can be developed into suitable bilayer tablets that are stable and capable of releasing the drugs over 12 h.
Chuan YWetal11investigated the compaction behaviour of binary mixtures and bilayer tablets of two common pharmaceutical excipients, microcrystalline cellulose and lactose. The effects ofcompositions and compaction pressure on the compaction behaviour of binary matrix mixtures and bilayer tablets are also explored. The delimitation phenomena during the manufacturing of bilayer tablets and fracture patterns of tablets subjected to diametrical compression are examined using X-ray computed tomography. It was also found that, using the same compaction process, the relative densities of the tablets were generally different when differentcompositions were used, especially when the maximum compression pressure is relatively low.
6.3 / Objective of the Study
The objectives of the proposed study are:-
1.Preformulation study of the drug candidates and polymer carriers
2.Preparation of bilayer matrix tablets of an antihypertensive by suitable methods
3.Evaluate the prepared bilayer matrix tablets
4.Stability studies of the selected formulations
7
7.1 / Materials & Methods
Source of data

The data will be obtained from the literature survey and Internet source
The data will be obtained from the experimental work, which includes formulation of bilayer tablets, evaluation and stability studies

7.2 / Method of collection of data (including sampling procedures if any)

Data on drug and Excipients will be collected from the drug information centre, Patents, Reference books, Text books, catalogs etc.
Data will be collected from the prepared formulations, in-vitro dissolution studies and stability studies as per ICH Guidelines. In- vitro Dissolution studies will be used as criteria for assessing the enhancement of oral bioavailability of poorly aqueous soluble drug.

7.3
7.4 / Materials
Drug : The antihypertensive Drugs will be Procured or obtained from suitable Pharma grade Manufacturer.
Polymer
The natural Biodegradable polymers, Synthetic Polymers.
All other chemicals will be used of analytical grade.
Methods
I. Preformulation studies
a. Preliminary morphological studies
b. Compatibility studies
II. Preparation bilayer matrix tablets

Wet granulation
Dry granulation
Direct compression

II. Evaluation studies
1. Evaluation of Granules
a. Preliminary morphological study
b. Physicochemicalstudy
2. Evaluation of Tablets
a. Preliminary morphological study
b. Physicochemical study
c. In vitro dissolution studies
d. Drug content
g. Content uniformity
i. Stability studies.
7.4 / Does the study require any investigations or interventions to be conducted
On patients or other human or animals? If so please describe briefly
NOT APPLICABLE
7.5 / Has the Ethical Clearance been obtained from your Institution in case of 7.4?
NO
8 / LIST OF REFERENCES

Chinam NP, Arethi BK, Hemant KP, Prakash S, Vimala DM.Design and evaluation of sustained release bilayer tablets ofpropranolol hydrochloride.Acta Pharm2007;57:479–89.

Ragvendra NG, Ashok Y, Upendra K. Formulation and evalution of zero-order release glipizide bilayer matrix tablets using natural and synthetic polymers. Int J Pharm 2010;2:34-42.

Nagaraju R, Rajesh K. Formulation and evaluation of bilayer Sustainedrelease tablets of Salbutamol and Theophylline. Int J Pharm 2009Oct-Dec;2(3):638-45.

Bhavesh S, Surendra G, Sanjay S. Formulation and evaluation of bi-layer tablet of metoclopramidehydrochloride and ibuprofen. AAPS Pharm Sci Tech 2008;9:818-27.

Efentakis M, NaseefH ,Vlachou M.Two- and three-layer tablet drug delivery systems for oral sustained release of soluble and poorly soluble drugs. Drug DevInd Pharm 2010;36(8):903-16.

Ramesh, Sathis KD, Guruviah, Harani A. Formulation and evalution of the bilayered matrix tablets of metformin Hcl Sr and pioglitazone. Am Euras J Sci Res 2010;5(3):176-82.

Sajjan A,Natasa SB. Stability of amlodipine besylate and atenolol in multi-component tablets of mono-layer and bi-layer types. Acta Pharm2008;(58):299–308.

Gohel MC, Parikh RK, Nagori SA, Jethwa. Fabrication and evalution of bilayer tablet containing conventional paracetamol and modified release diclofenac sodium. Indian J Pharm Sci 2010;72(2):191-6.

Rakesh KD, Kunchu K, Theetha GT. Preparation and evaluation of sustained release matrix tablets of tramadol hydrochloride using glyceryl palmitostearate. Trop J Pharm Res 2010 June;9(3):275-81.

Naeem MA, Mahmood A, Khan SA, Shahiq Z. Development and evaluation of controlled release bilayer tablets containing microencapsulated tramadol and acetaminophen. Trop J Pharm Res 2010 Aug;9(4):347-54.

Chuan YW, Jonathan PKS. A comparative study of compaction properties of binary and bilayer tablets. Powder Technol 2009;189:285–94.

9 / Signature of the Candidate / (PATEL TARUNKUMAR VITTHALBHAI)
10 / Remarks of the Guide
The topic selected for dissertation is satisfactory. Adequate equipment & chemicals are available to carry out the project work.
11 / Name & Designation (in BLOCK LETTERS)
11.1 Guide / MR.S RAJARAJAN. M.PHARM (Ph.D)
ASSISTANT PROFESSOR
DEPT. OF PHARMACEUTICS
KARNATAKACOLLEGE OF PHARMACY
11.2 Signature of Guide / s. OHINI. M.)
11.3 Co-Guide / NOT APPLICABLE
11.4 Signature of Co-Guide / NOT APPLICABLE
11.5 Head of the Department / DR. K. RAMESH
PROFESSOR AND HEAD
DEPARTMENT OF PHARMACEUTICS
KARNATAKACOLLEGE OF PHARMACY
11.6 Signature of HOD
12 / 12.1 Remarks of the Principal
All the required facilities will be provided to carry out dissertation work under the supervision of the guide.
12.2 Signature of thePrincipal / ( DR. K.RAMESH )