INTRODUCTION:

Oral drug administration is the most preferable and oldest route for drug delivery. This is due to the low cost of medicine preparation and ease of administration, which makes it the most favorable route of drug administration for patients.^{1, 2
It} has been known as the most popular and successful route for controlled delivery of fast release drugs because of greater flexibility in the designing of dosage forms compared to other routes³. Previous reviews reported that more than 50% of the medications which are available in the market were found to be given orally.^{4, 5}

Matrix tablets:

Introduction of matrix tablet as controlled release has given a new breakthrough for novel drug delivery system in the field of Pharmaceutical technology^. These technologies have often proven popular among the oral controlled drug delivery technologies due to their simplicity, ease in mechanized, elevated level of reproducibility, stability of the raw materials and dosage form, and simplicity of scale up and process validation^. Matrix tablet is a promising approach for the establishment of extended-release drug therapy as tablets offer the lowest cost approach to controlled release oral solid dosage forms. Matrix tablets may be defined as the “oral solid dosage forms in which the drug or active ingredient is homogeneously dispersed throughout the hydrophilic or hydrophobic matrices which serves as release rate retardants”. Matrix tablets are the type of controlled drug delivery systems, which release the drug in continuous manner. In a matrix system, the drug substance is homogenously mixed into the rate controlling material as crystalline, amorphous or in rare cases molecular dispersion.³These release the drug by dissolution controlled and/or diffusion controlled mechanisms.⁴

In gastric pH environment, matrix tablet gradually erodes alternatively at a pH corresponding to the upper small intestine; the tablet disintegrates rapidly to reduce coated particles, which in turn slowly releases drug.

Research on oral drug delivery with either further development in the delivery system or novelty in the drug formulation is ongoing work for many formulation scientists ⁶. The most prominent requirements for a drug delivery system to make it novel are, first to deliver a drug at a controlled rate, and second to pass the active entity to the target site for action. Formulation scientists have been used many possible approaches to achieve this challenging novelty in oral drug formulation, either by unifying drug distribution into a carrier system, or by controlling drug release in the blood to reach the designed plasma drug concentration-time profile.^{7 ,8}

In order to overcome the drawbacks of conventional drug delivery systems, several technical advancements have led to the development of controlled drug delivery system that could revolutionize method of medication and provide a number of therapeutic benefits.³

Controlled release drug delivery systems can offer temporal and/or locative control over the release of drugs. Thus, the oral controlled release drug delivery system is the most widely used system for controlling the release of drugs given orally.⁹Many advantages for this system were reported, such as preventing plasma drug level fluctuations, reducing dosing frequency of drug administration, enhancing drug bioavailability, improving patient compliance and minimizing side effects and toxicity of drugs.¹⁰In comparison, the conventional oral drug dosage form has a number of shortcomings such as, high tendency of plasma drug level fluctuations, increasing the dosing frequency of drug administration, time limitation for drug electiveness at the target site of action and low oral bioavailability of some drugs due to interaction with food or unsuitable gut environment, for example cefotaxime Na.¹¹

Advantages of Matrix Tablets: ^5,13

· Easy to manufacture.

· Versatile, and effective

· It has low cost.

· Can be made to release high molecular weight compounds.

· Suitable for both non degradable and degradable systems.

· No danger of dose dumping in case of rupture.

· Can be fabricated in a wide range of sizes and shapes.

Limitations of Matrix Tablets:

· The remaining matrix must be removed after the drug has been released.

· The drug release rates vary with the square root of time.

· Achievement of zero order release is difficult.

· Not all drugs can be blended with a given polymeric matrix

Disadvantages of matrix tablet:^11,12

· The remaining matrix must be removed after the drug has been released.

· High cost of preparation.

· The release rates are affected by various factors such as, food and the rate transit through the gut.

· The drug release rates vary with the square root of time.

· Release rate continuously diminishes due to an increase in diffusional resistance and/or a decrease in effective area at the diffusion front. However, a substantial sustained effect can be produced through the use of very slow release rates, which in many applications are indistinguishable from zero order.

Various systems of oral controlled release dosage forms:-

Various techniques have been used in the preparation of the controlled release drug delivery system; most of them working under the principle of slowing the dissolution rate of the drug from the dosage form. In general, controlled release formulations can be divided into different categories based on methods of preparation and/or the mechanisms of drug release, which will be shown in the following below.

Matrix system

The matrix system is the most commonly used controlled release delivery system of rapidly released drugs. The drug is uniformly dissolved or dispersed in suitable polymeric materials. Most of these materials have either hydrophilic or hydrophobic properties, in which the retardant material and drug are homogeneously distributed or dissolved in the polymeric matrix. This is done either by wet granulation or by the direct compression technique in the solid dosage form, where the drug is embedded in the matrix core of the retardant ^{15 .}Therefore, this matrix system is characterized by drug dispersed materials in the polymer blend . Drug release is controlled by gradual dissolution of the matrix or gradual leaching of the drug from the retardant material.

A range of controlled release mechanisms have been explained, including diffusion through matrices or across membranes and erosion. However, knowing the material properties of the matrices is essential to predict the mechanism of drug release. The matrix system of oral controlled release delivery system of drugs is classified according to polymer type, porosity sizes and other miscellaneous ways of matrix preparation.

Classifications of matrix system based on polymer type:-

1) Hydrophilic matrix system

Hydrophilic matrix can be utilized as a means to control the drug release rate. The matrix may be tabulated by direct compression of the blend of active ingredient and certain hydrophilic carriers or from a wet granulation containing the drug and hydrophilic matrix materials. The hydrophilic matrix requires water to activate the release mechanism and explore several advantages, including ease of manufacture and excellent uniformity of matrix tablets. Upon immersion in drug release is controlled by a gel diffusion barrier that is formed and tablet erosion. The effect of formulation and processing variables on drug release behavior from compressed hydrophilic matrices has been studied by number of investigators. The matrix building material with fast polymer hydration capability is the best choice to use in a hydrophilic matrix tablet formulation. An inadequate polymer hydration rate may cause premature diffusion of the drug and disintegration of the tablet owing to fast penetration of water. It is particularly true for formulation of water soluble drug.

Hydrophilic polymer matrix systems are widely used in oral controlled drug delivery because of their flexibility to obtain a desirable drug release profile, cost effectiveness, and broad regulatory acceptance. The formulation of the drugs in gelatinous capsules or more frequently, in tablets, using hydrophilic polymers with high gelling capacities as base excipients is of particular interest in the field of controlled release. Infect a matrix is defined as well mixed composite of one or more drugs with a gelling agent (hydrophilic polymer). These systems are called swellable controlled release systems. The polymers used in the preparation of hydrophilic matrices are divided in to three broad groups,

A) Cellulose derivatives

· Hydroxyethyl cellulose,

· Hydroxypropylmethyl cellulose (HPMC) 25, 100, 4000 and 15000 cps,

· Sodium carboxyl methyl cellulose

B) Non-cellulose natural or semi synthetic polymers

· Agar-agar, Carob Gum, Alginates,

· Molasses, Polysaccharides of mannose and

· Galactose, Chitosan and Modified starches.

C) Polymers of acrylic acid

· Polymer which is used in acrylic acid category is Carbopol 934.

2) Hydrophobic Matrices:¹³

The concept of using hydrophobic or inert materials as matrix materials was first introduced in 1959. In this method of obtaining sustained release from an oral dosage form, drug is mixed with an inert or hydrophobic polymer and then compressed in to a tablet. Sustained release is produced due to the fact that the dissolving drug has diffused through a network of channels that exist between compacted polymer particles. Examples of materials that have been used as inert or hydrophobic matrices include polyethylene, polyvinyl chloride, ethyl cellulose and acrylate polymers and their copolymers. The rate-controlling step in these formulations is liquid penetration into the matrix. The possible mechanism of release of drug in such type of tablets is diffusion. Such types of matrix tablets become inert in the presence of water and gastrointestinal fluid.

In this type of matrix system, a hydrophobic polymer material is granulated with a drug by using latex or pseudo latex as granulating fluid. Examples of materials used in this system are: polyvinyl chloride, ethyl cellulose, cellulose acetate and polystyrene ^{15, 17, 18 .}

Controlled release tablets based upon an inert compressed plastic matrix have been used extensively. Release is usually delayed because the dissolved drug has to diffuse through capillary network between the compacted polymer particles. Plastic matrix tablets, in which the active ingredient is embedded in a tablet with coherent and porous skeletal structure, can be easily prepared by direct compression of drug with plastic materials provided the plastic material can be comminute or granulated to desired particle size to facilitate mixing with the drug particle. In order to granulate for compression into tablets, the embedding process may be accomplished by,

1. The solid drug and the plastic powder can be mixed and kneaded with a solution of the same plastic material or other binding agent in an organic solvent and then granulated.

2. The drug can be dissolved in the plastic by using an organic solvent and granulated upon evaporation of the solvent.

3. Using latex or pseudo latex as granulating fluid to granulate the drug and plastic masses. For example: Polyvinyl chloride, Ethyl cellulose, Cellulose acetate and Polystyrene.

3) Fat-wax matrix system

In this type of matrix system, lipid waxes or other related materials are used in the preparation of the matrices. The drug released in this system occurs through both pore diffusion and erosion. The matrices are more sensitive to digestive fluid in the gut as compared to an insoluble polymer matrix . Examples of retardant materials used in the matrix bases of this system are: carnauba wax in combination with stearyl alcohol or stearic acid.¹⁸

4) Biodegradable matrix system

In this type of matrix system, the polymeric materials used consist of monomers which are linked to each other through functional groups with instable functionality. The degradation of polymeric materials into oligomers and monomers occurs through either biological enzymes produced by surrounding tissues or non-enzymatic processes.¹⁹Examples of natural polymers used in this matrix base are proteins, polysaccharides, aliphatic polyesters, and polyanhydrides are synthesized polymers.²⁰

5) Mineral matrix system

In this type of matrix system, the polymeric material used is hydrophilic carbohydrate and it can be obtained from different species of brown seaweeds by the use of dilute alkali ¹⁹.

Classifications of matrix system based on porosity size: -^21,22.

A) Macro-porous matrix system

In this type of matrix system, drug diffusion occurs through pores with a size range of 0.1 to 1 μm. This system is suitable for drug molecules with molecular sizes less than 1 μm.

B) Micro-porous matrix system

In this type of matrix system, drug diffusion occurs through pores with a size range of 50 up to 200 A °. This system is suitable for small drug molecules with molecular sizes less than 200 A°.

C) Non-porous matrix system

In this type of matrix system, drug diffusion occurs through the network meshes rather than by diffusion through small pores.

Classifications based on other miscellaneous way of matrix preparations:-

A) Multilayered matrix system

In this type of matrix system, the matrix core is made of hydrophilic substances in which the drug molecules are coated with a semi-permeable polymeric material. This semi-permeable polymeric material is utilized as a barrier-layer on both surfaces of the core during preparation.²³An alteration of the swelling rate of the core can occur due to the presence of barrier-layers, resulting in minimizing the surface area for drug molecules during the release process. Different drug release profiles can be obtained by varying the geometry of the barrier-layer in the matrix.²⁴The drug release is controlled by swelling, gelling and finally dissolving the barrier-layers of the matrix.

B) Floating matrix system

In this type of matrix system, the bulk density of the matrix is lower than the gastric fluid in the stomach. After creating buoyancy in the stomach, the release of drug molecules from the matrix can occur slowly. Drug release can occur over a long period of time, which prolongs gastric residence time and thereby increases the bioavailability of fast release drug molecules²⁵. Diltiazem HCl is one of the examples of a fast release drug which was successfully prepared in a controlled release using the floating matrix system ²⁶and detected on the sensitive HPLC method ²⁷. The steady release of drug from this hydrophilic matrix system is supported by control of the buoyancy effect and continuous release. HPMC is a widely used polymer in this type of hydrophilic matrix system. It has a pH independent gelling agent property. As a result of this effect, swelling and erosion mechanisms can be obtained together to control and slow down the fast release drug in a steady manner²⁵.

C) pH sensitive matrix system

In this type of matrix system, an enteric coating of the solid dosage form can provide protection for the drug from the harsh acidic media of the stomach. Thus, low pH sensitive drug molecules can reach the small intestine and colon safely. This type of matrix system is applicable to protect antigen or protein molecules from the harsh acidic media of the stomach after oral administration. PH sensitive polymers such as HPMC-phthalate or cellulose acetate phthalate can be used in this type of matrix system.²⁸These types of polymers are pH-sensitive materials. This matrix system works by releasing the enteric coated drug at a specifically high pH value in the GIT, where drug absorption can occur in the right location.

D) Mucoadhesive matrix system

In this type of matrix system, the drug is released over a controlled period of time. The targeted tissues can be ocular, respiratory, gastrointestinal, buccal, nasal, rectal, urethral and vaginal tissues. In addition, this type of matrix system can be applied to any mucosal tissue in the body in the GIT. The used materials in this system are swellable hydrophilic polymers which can interact with the glycoproteins being available in the mucous layer of the gut.²⁹

Polymers used in the matrix:-

The polymers most widely used in preparing matrix system include both hydrophilic and hydrophobic polymers.

(A) Hydrophilic Polymers

Hydroxyl propyl methyl cellulose (HPMC),hydroxyl propyl cellulose(HPC), hydroxyl ethyl cellulose (HEC), Xanthan gum, Sodium alginate, poly(ethylene oxide), and cross-linked homo polymers and co-polymers of acrylic acid.

(B) Hydrophobic Polymers

This usually includes waxes and water insoluble polymers in their formulation.

(C) Waxes

Carnauba wax, bees wax, candelilla wax, micro crystalline wax, ozokerite wax, paraffin waxes and low molecular weight polyethylene.

(D) Insoluble polymers

Ammonium ethacrylateco-polymers (Eudragit RL100, PO, RS100, PO), ethyl cellulose, cellulose acetate butyrate, cellulose acetate propionate and latex dispersion of meth acrylic ester copolymers.

Components of matrix tablets:³⁰^.

These include:

· Active drug

· Release controlling agent(s): matrix formers

· Matrix Modifiers, such as channeling agents and wicking agents

· Solubilizes and pH modifiers

· Lubricants and flow aid

· Supplementary coatings to extend lag time further reduce drug release etc.

· Density modifiers (if required)

· Matrix formers:

Hydrophobic materials that are solid at room temperature and do not melt at body temperature are used as matrix formers. These include hydrogenated vegetable oils, cotton seed oil, soya oil, microcrystalline wax and carnauba wax. In general such waxes form 20-40% of the formulation.

· Channeling agents:

These are chosen to be soluble in gastrointestinal tract and to leach from the formulation, so leaving tortuous capillaries through which the dissolved drug may diffuse in order to be released. The drug itself can be a channeling agent but a water soluble pharmaceutical acceptable solid material is more likely to be used. Typical examples include sodium chloride, sugars and polyols. This choice will depend on the drug and desired released characteristics. These agents can be 20-30% of the formulation.

· Solubilizes and pH modifiers: It is often necessary to enhance the dissolution of drug. This may be achieved by the inclusion of solubilizing agents such as PEGs, polyols and surfactants. If the drug is ionisable then the inclusion of buffers or counter ions may be appropriate. On occasions the dissolution enhancer may also be the channeling agent.

· Anti-adherent or glidants: Heat is generated during compaction of the matrix can cause melting of the wax matrix forming compounds and sticking to the punches. Something is needed to cope with the sticking; suitable anti adherents include talc and colloidal silicon dioxide. These materials also can act as glidants and improve the flow of formulations on the tablet machine. The typical amounts used will depend on the anti-adherent used, for example 0.5-1% for colloidal silicon dioxide and 4-6% for talc. Magnesium stearate, if added, can also act as an anti-adherent.

Methods used to achieve controlled release of orally

Administered drugs: ³¹

A. Diffusion Controlled System:

Basically diffusion process shows the movement of drug molecules from a region of a higher concentration to one of lower concentration. This system is of two types:

a) Reservoir type: A core of drug surrounded by polymer membrane, which controls the release rate, characterizes reservoir devices.

b) Matrix type: Matrix system is characterized by a homogenous dispersion of solid drug in a polymer mixture.

B. Dissolution Controlled Systems:

a) Reservoir type:

Drug is coated with a given thickness coating, which is slowly dissolved in the contents of gastrointestinal tract. By alternating layers of drug with the rate controlling coats as a pulsed delivery can be achieved. If the outer layer is quickly releasing bolus dose of the drug, initial levels of the drug in the body can be quickly established with pulsed intervals.

b) Matrix type:

The more common type of dissolution controlled dosage form. It can be either a drug impregnated sphere or a drug impregnated tablet, which will be subjected to slow erosion.

C. Bioerodible and Combination of Diffusion and Dissolution Systems:

It is characterized by a homogeneous dispersion of drug in an erodible matrix.

Method of Preparation matrix tablet:-

Fig:- 2 Method of preparation of matrix tablet

Basic principle of drug release: ³²

In solution, drug diffusion will occur from a region of high concentration to the region of low concentration. This concentration gradient is the driving force for the drug diffusion, out of a system. Water diffuses into the system in analogous manner. There is an abundance of water in the surrounding medium and system should allow water penetration. The inside of the system has low water content initially than the surrounding medium.

Fig:-3 Drug release in matrix tablet

Factors affecting drug release from matrix tablets:-

1. Swelling characteristics of polymers

2. Polymer erosion

3. Drug loading

4. Drug solubility

Evaluation parameter:

Prepared tablets were evaluated for certain physical properties like uniformity of weight, hardness, friability and dissolution study etc.

1) Weight variation test

To study weight variation, 20 tablets of each formulation were weighed using an electronic balance and the test was performed according to the official method.³³

2) Uniformity of weight

Every individual tablet in a batch should be in uniform weight and weight variation in within permissible limits. The weights were determined to within ±1mg. Weight control is based on a sample of 20 tablets.

3) Dimensions

The dimensions (diameter and thickness) were then determined to within ± 0.01 mm by using digital vernier calipers.³⁴Thickness of the tablets was determined using a vernier caliper.⁶

4) Hardness

The hardness of the tablets was determined by diametric compression using a Hardness 33 testing apparatus (Monsanto Type). A tablet hardness of about 4-5 kg is considered adequate for mechanical stability. Hardness of the tablets was determined using a hardness testing apparatus (Monsanto Type). A tablet hardness of about 5-6 kg/cm2 is considered adequate for mechanical stability.³⁵

5) Friability

The friability of the tablets was measured in a Roche friabilator. Tablets of a known weight (W0) or a sample of tablets is dedusted in a drum for a fixed time (100 revolutions) and weighed (W) again. Percentage friability was calculated from the loss in weight as given in equation as below. The weight loss should not be more than 1% w/w.10

% Friability = (W0-W)/ W0 × 100

6) In-vitro dissolution study

The release rate of tablet was determined using United State Pharmacopoeia (USP) dissolution testing apparatus II (paddle method). The dissolution test was performed using 900 ml solvent and set RPM. A sample of the solution was withdrawn from the dissolution apparatus at different time interval. The samples were replaced with fresh dissolution medium of same quantity. The samples were filtered through a membrane filter. Absorbance of these solutions was measured using a UV is double beam spectrophotometer³⁶.

List of various drugs which can be formulated as a matrix tablet with polymer and method used or its preparation are shown in (Table 1).

Drugs used	Category	Method used	Polymer used
Carbose	Anti-diabetic	Direct Compression	HPMC, Eudragit
Aceclofenac	Anti-inflammatory	Wet Granulation	HPMC-K4M,K15M, K100M,E15,EC, Guar gum
Ambroxol HCL	Expectorent, Mucolytic	Direct Compression	HPMC-K100M,
Aspirin	Anti-inflammatory	Direct Compression	EC, Eudragit-RS100, S100
Amlodipine	Anti-arrythmatic	Direct Compression	HPMC, EC
Alfuzosin	Alfa-adrenergic Agonist	Direct Compression	HPMC-K15M, Eudragit-RSPO
Chlorphenarimine maleate	H1 antagonist	Melt-extrusion	Xanthan gum,Chitoson
Domperidone	Anti-emetic	Wet Granulation	HPMC-K4M, Carbopol-934
Diclofenac Na	Anti-inflammatory	Wet Granulation	Chitoson, EC, HPMCP, HPMC
Diethylcarbamazepine citrate	Anti-filarial	Wet Granulation	Guar gum, HPMC-E15LV
Diltiazem	Ca+2 channel blocker	Direct Compression	HPMC-K100M, HPMC- K4M, Karaya gum, Locust bean gum, Sod.CMC
Furosemide	Anti-diuretic	Direct Compression	Guar gum, Pectin,
Enalpril meleate	ACE inhibitor	Direct Compression	HPMC-K100M,HPMC K4M,

REFERENCES:-

1. Patel KK, Patel MS, Bhatt NM, Patel LD, Pathak NL, Patel KJ. An overview: extended release matrix technology. Int J Pharm Chem Sci 2012;1(2):828-43.

2. Sanap SL, Savkare AD. Controlled porosity osmotic pump: a review. Int J Pharm Res Dev 2014;5(12):70-80.

3. Gahlyan M, Jain S. Oral controlled release drug delivery system-a review. Pharmatutor 2014;2(8):170-8.

4. Kumar S, Kumar A, Gupta V, Malodia K, Rakha P. Oral extended release drug delivery system: a promising approach. Asian J Pharm Tech 2012;2(2):38-43.

5. Kumar S, Kumar H, Kumar R, Kumar A, Malodia K. Design, development and characterization of salbutamol sulphate extended release matrix tablets. Res J Pharm Biol Chem Sci 2013;4(3):270-7.

6. Keraliya RA, Patel C, Patel P, Keraliya V, Soni TG, Patel RC, et al. Osmotic drug delivery system as a part of modified release dosage form. ISRN Pharm 2012;2012:1-9.

7. Pandita A, Sharma P. Pharmacosomes: an emerging novel vesicular drug delivery system for poorly soluble synthetic and herbal drugs. ISRN Pharm 2013;2013:1-10.

8. Khirwadkar P, Singh D, Dashora K. Microchip technology: a new approach in novel drug delivery system. IJBAR 2012;3(3):149-61.

9. Dixit N, Maurya SD, Sagar BPS. Sustained release drug delivery system. Indian J Res Pharm Biotech 2013;1(3):305-10.

10. Kotha R, Raghavapally SG, Adavi SL, Taranali S, Pandey D. Current techniques in pulsatile drug delivery: a review. Int Res J Pharm 2013;4(3):77-84.

11. Arafat M, Golocorbin-Kon S, Mikov M. The measurement of cefotaxime sodium in rat plasma after oral administration: a sensitive HPLC-UV method. Int J Pharm Pharm Sci 2015;7(4):343-6.

12. Moodley K, Pillay V, Choonara YE, du Toit LC, Ndesendo VMK, Kumar P, et al. Oral drug delivery systems comprising altered geometric configurations for controlled drug delivery. Int J Mol Sci 2013;13(1):18-43.

13. Narasimharao R, Anusha RM, Swetha RN, Divyasagar P, Keerthana K. Design and evaluation of metformin hydrochloride extended release tablets by direct compression. Int J Res Pharm Biomed Sci 2011;2(3):1118-33.

14. Kumar KPS, Bhowmik D, Dutta A, Paswan S, Deb L. Recent trends in scope and opportunities of control release oral drug delivery systems. Crit Rev Pharm Sci 2012;1:20-33.

15. Pundir S, Badola A, Sharma D. Sustained release matrix technology and recent advance in matrix drug delivery system: a review. Int J Drug Res Tech 2013;3(1):12-20.

16. Rao NGR, Sounya P, Revathi K, Nayak BS. A review on pulastile drug delivery system. Int Res J Pharm 2013;4(3):31-44.

17. Rathore AS, Jat RC, Sharma N, Tiwari R. An overview: matrix tablet as controlled drug delivery system. Int J Res Dev Pharm Life Sci 2013;2(4):482-92.

18. Jaimini M, Kothari AH. Sustained release matrix type drug delivery system: a review. J Drug Delivery Ther 2012;2(6):142-8.

19. Rancan F, Blume-Peytavi U, Vogt A. Utilization of biodegradable polymeric materials as delivery agents in dermatology. Clin Cosmet Invest Dermatol 2014;7:23-34.

20. Lieberman HA, Lachman L, Schwartz JB. Pharmaceutical Dosage Forms: Tablets. 2nd ed. New York/Basel: Marcel Dekker; 1990. p. 195-246.

21. Gren T, Bjerre C, Camber O, Ragnarsson G. In vitro drug release from porous cellulose matrices. Int J Pharm 1996;141(1-2):53-62.

22. Efentakis M, Peponaki C. Formulation study and evaluation of matrix and three-layer tablet sustained drug delivery systems based on carbopols with isosorbitemononitrate. AAPS Pharm Sci Tech 2008; 9(3):917-23.

23. Syed IA, Mangamoori LN, Rao YM. Formulation and characterization of matrix and triple-layer matrix tablets for controlled delivery of metoprolol tartrate. Int J Pharm Sci Drug Res 2011;3(1):23-8.

24. Sathiyaraj S, Devi RD, Hari VBN. Lornoxicam gastro retentive floating matrix tablets: Design and in vitro evaluation. J Adv Pharm Technol Res 2011;2(3):156-62.

25. Gambhire MN, Ambade KW, Kurmi SD, Kadam VJ, Jadhav KR. Development and in vitro evaluation of an oral floating matrix tablet formulation of diltiazem hydrochloride. AAPS Pharm Sci Tech 2007;8(3):1-9.

26. Arafat M. Simple HPLC validated method for the determination of diltiazem hydrochloride in human plasma. Int J Pharm Pharm Sci 2014;6(9):213-6.

27. Arafat Int J Pharm Pharm Sci, Vol 7, Issue 7, 16-21 20

28. Balamuralidhara V, Pramod kumar TM, Srujana N, Venkatesh MP, Gupta NV, Krishna KL, et al. pH sensitive drug delivery systems: a review. Am J Drug Discovery Dev 2011;1(1):24-48.

29. Arora G, Malik K, Singh I, Arora S, Rana V. Formulation and evaluation of controlled release matrix mucoadhesive tablets of domperidone using saliva plebeian gum. J Adv Pharm Technol Res 2011; 2(3):163-9.

30. Mishra B, Sankar C, Dilip C, Pravitha V, Raj A, Sadique TA. Osmotically controlled diclofenac sodium tablets: membrane and osmogens effects. Pharm Lett 2010;2(6):21-7.

31. Babu CA, Rao MP, Vijaya RJ. Controlled-porosity osmotic pump tablets-An overview. J Pharm Res Health Care 2010;2(1):114-26.

32. Krishanaiah YS, Lath K, Nageshwara L, Karthikeyan RS, Bhaskar P and Satyanarayana V. Development of colon target oral guar gum matrix tablet of Albendazole for the treatment of Helminthiasis. Indian J. Pharm. Sci. 2003; 65 (4): 378-385

33. British Pharmacopoeia, vol. 2. Her Majesty’s stationary office, London,England.2000: 266-268

34. Lachman. L, Liberman. A, Kinig. J.L. The theory and practice of industrial Pharmacy, 4th edition, Varghese publishing house, Bombay.1991:67-68

35. The British Pharmacopoeia, department of health/by stationary office on behalf of the medicine and health care product regulatory agency, crown copy right, 2005; 5th Ed. 1303-1304, 2588-2589, A133.

36. Godbillon J, Gereedin A, Richard J, Leroy D, Mopprt J. Osmotically controlled delivery of metoprolol in man: in vivo performance of oros systems with different duration of drug release. Br J Clin Pharmacol 1985;19(2):213-8.

Received on 01.12.2015 Accepted on 15.12.2015

Asian J. Pharm. Tech. 2015; Vol. 5: Issue 4, Oct. - Dec., Pg 214-221

DOI: 10.5958/2231-5713.2015.00031.8