INTRODUCTION:

The goal of any drug delivery system is to provide a therapeutic amount of drug to the proper site in the body to achieve promptly and then maintain the desire drug concentration. The absorption of drugs takes place in certain regions of the gastrointestinal (GI) tract, usually the upper intestinal tract. There are currently limited formulation methods and no marketed products to provide sustained input for such drugs (with an absorption window in the gastrointestinal tract) from an oral formulation without reducing the bioavailability. The modified enteric-coated formulation that provide immediate release in the small intestine and simultaneously provide sustained input of drugs that have an absorption window and at the same time may improve or maintain bioavailability of the formulation.¹

Enteric-coated dosage forms are especially suited for administration of drugs which are not stable in gastric fluids or can cause irritation of gastric mucosa and which are absorbed in the duodenum or upper intestine. After the acid-resistant coating has dissolved in the intestine, immediate drug release is essential.²

The action of enteric coating results from difference in composition of the respective gastric and intestinal environments in regard to pH and enzymatic properties.

Although there have been repeated attempts to produce coating that are subject to intestinal enzyme breakdown, this approach is not popular, since enzymatic decomposition of the film is rather slow. Thus, most currently used enteric coatings are weak acids that remain undissociated in the low pH environment of the stomach but readily ionize when pH rises to about 5.³

The in vitro disintegration of products coated with common enteric polymers (cellulose esters, polyvinyl derivatives, and polymethacrylates) occurs over a very short period of time, normally within 30 min in pH 6.8 phosphate buffer. However, this is not reflected in vivo; gamma scintigraphy studies have shown that it can take up to 2 h for such products to disintegrate in the human small intestine. Drug release will then occur in the distal small intestine and cause a delayed response to medication and potentially reduce the bioavailability of those drugs having an absorption window in the proximal small intestine. This in vivo/in vitro discrepancy is due in part to the inadequacy of the commonly used in vitro dissolution medium (compendial pH 6.8 phosphate buffer) to resemble the luminal conditions of the upper small intestine in many respects such as pH, ionic composition, buffer capacity, viscosity and volume.⁴

Benefit of enteric coated drug delivery system

v To protect acid-labile drug from the gastric fluid.

v To prevent gastric distress or nausea due to irritation from a drug.

v To deliver drug intended for local action in the intestine.

v To deliver drug that are optimally absorbed in the small intestine to their primary absorption side in their most concentration form.

v To provide delayed-release component for repeat-action.⁵

v Reduction in health care cost through improved therapy, shorter treatment period and less frequency of dosing.

v Maximum utilization of drug enabling reduction in total amount of dose administered.

v Improve patient convenience and compliance due to less frequent administration.

Risk of enteric coated drug delivery system:

v Poor In-vitro in-vivo correlation.

v Decreased systemic availability in comparison to immediate release conventional dosage form: this may due to incomplete release, increased first pass metabolism, increased instability insufficient residence time for complete release, site specific absorption and pH dependent solubility etc.

v Possibility of dose dumping to food physiologic or formulation variables or chewing or grinding of oral formulation by the patient and thus increased risk of toxicity.

v Retrieval of drug is difficult in case of toxicity, poisoning or hypersensitive reactions.

v High cost of formulation.⁶

Enteric polymer:

These materials are applied either dissolved in an organic solvent or as an aqueous dispersion. Traditionally, it has been the practice to restrict enteric polymers dissolving at pH 7 and above for colon targeting. Selection of enteric polymer dissolving at pH ≥ 7 and Optimization of coat thickness is essential to ensure drug release in the entire gastrointestinal tract. The list of enteric polymeric materials commercially available is given in Tables 1-3. Adjustments to the thickness of enteric polymer coat will help to extend the choice to those dissolving at pH less than 7. Employment of imaging techniques, especially scintigraphy of the formulation in the gastrointestinal tract, has been found to be a useful tool in optimizing coat thickness.

Table 1 Phthalate-Based Enteric Polymers

A number of phthalate-based enteric polymers have been exploited commercially

Polymer	Threshold pH	Brand name	Manufacturer
Cellulose acetate phthalate	6.0–6.4	C-A-P Aquacoat CPD	Eastman FMC
Hydroxypropyl methylcellulose	4.8	H.P.M.C.P. 50	Eastman
phthalate 50		HP-50	Shin-Etsu
Hydroxypropyl methylcellulose	5.2	H.P.M.C.P. 55	Eastman
phthalate 55		HP-55	Shin-Etsu
Polyvinylacetate phthalate	5.0	Sureteric	Colorcon

Table 2 Methacrylic Acid–Based Copolymers

Polymer

Threshold pH

Brand names

Manufacturer

Methacrylic acid–

Methyl methacry-

late copolymer (1:1)

6.0

Eudragit L 100/L 12.5

Rohm

GmbH

Methacrylic acid–

Methyl methacry-

late copolymer (2:1)

6.5–7.5

Eudragit S 100/S 12.5

Rohm

GmbH

Methacrylic acid–ethyl

acrylate copolymer

(2:1)

5.5

Eudragit L 100-55/L 30 D-55

Acryl-EZE

Eastacryl 30D

Rohm

GmbH

Colorcon

Eastman

Hydroxypropyl methyl cellulose:

It is a cellulose derivative in which some of the hydroxyl groups are substituted with methyl and hydroxypropyl groups. HPMC has many of the desired coating polymer properties: it forms a transparent, tough and flexible film that protects fragile tablets, masks the unpleasant taste of a drug and improves the appearance. HPMC is stable in the presence of heat, light, air and moisture in room conditions, although it is moderately hygroscopic. Aqueous film coating using HPMC, however, has proven complex and more sensitive to changes in the process compared to those of organic solvent coating (Nagai et al., 1997).⁸

Table 3 Miscellaneous Enteric Polymers

Polymer	Threshold pH	Brand names	Manufacturer
Shellac	7.0	—	Zinsser
Hydroxypropyl methylcellu- lose acetate succinate (HPMCAS)	7.0	Aqoat AS-HF	Pangaea Sciences Shinetsu
Poly (methyl vinyl ether/ maleic acid) monoethyl ester	4.5–5.0	Gantrez ES-225	ISP
Poly (methyl vinyl ether/ maleic acid)n-butyl ester	5.4	Gantrez ES-425	ISP

Coating solution:

The manufacturer is whether to use an aqueous coating or an organic coating system. Both have advantages and disadvantages. Whereas organic coating provides greater protection against moisture uptake during the coating process (important for moisture-sensitive ingredients) and are easier to apply because of the fast evaporation of solvents, the problems related to environmental control of organic solvents going in the atmosphere, the need to perform solvent residue tests, and the need to have explosion-proof facilities often yields to these advantages of aqueous coating systems. In recent years, many developments in the formulation of aqueous coatings made them an almost universally accepted mode of application.⁹

The selection of different types of solution used in enteric coating is based on the polymer solubility in solvent. 6-8 % increase in weight of the tablets is required to get desired acid resistant and impermeability. The solvent used in coating are acetone, purified water, alcohol, methylene chloride¹⁰ Chloroform, Methylene ethyl ketoneand porogen was used as the coating solution. The concentration of coating solution was above 4%, the viscosity of the coating solution would be too great to finish the coating process. When the concentration of the coating solution is lower than 2%, the coating membrane would be difficult to form. So, 3% (g/100ml) coating solution was chosen as the coating solution.¹¹The coating solution must be formulated to have a sprayable solution viscosity. Generally this means a viscosity of the coating solution in the range of 150-400 mPa•s, although higher viscosities may be possible under certain equipment conditions. Formulations may contain optional surfactants, plasticizers, or pigments. It should be noted, however, that these additional excipients can affect the viscosity of the coating solution. Yet the major factor controlling the formulation is the viscosity of the polymer grade being used and the concentration of polymer in the solution.¹²

Coating equipment:

A modern tablet coating system combines several components: a coating pan, a spraying system, an airhandling unit, a dust collector, and the controls. The coating pan is actually a perforated drum that rotates within a cabinet. The cabinet enables you to control airflow, air temperature, air pressure, and the coating application. The spraying system consists of several spray guns mounted on a manifold, a solution pump, a supply tank and mixer, and an air supply. The pump delivers the coating solution to the guns, where it combines with atomizing air to create a fine mist that is directed at the bed of tablets in the coating pan. The air handling unit heats and filters the air used to dry the coating on the tablets. Depending on your circumstances, it may include a humidifier or dehumidifier. The dust collector extracts air from the coating pan and keeps a slightly negative pressure within the cabinet. The controls enable you to orchestrate the operation of all the components to achieve the desired results. Once you load a batch of tablets into the coating pan, you need to preheat the tablets and allow time for dust and tablet flash to exit the pan. Once the temperature of the outlet air reaches 42° to 46°C, usually within 15 minutes, spraying can begin. The spray guns create a fine mist of coating solution that dries just after it contacts the tablet. As the water evaporates, it leaves the solids behind to form a thin film on the tablet. The key to tablet coating is to get the surface slightly wet and immediately dry. Your objective is to apply the coating in many short, fast exposures, not in long, slow exposures.¹³

Conventional coating pan are subglobular, pear shaped, or even hexagonal with a single front opening through which materials and processing air enter and leave. Their axis is normally inclined at approximately 45⁰to the horizontal plane and they are rotated between 25 to 40 rpm, the precise speed depending, most often, on the product involved. One modification of the normal pan has been the substitution of a cylindrical shape, rotted horizontally with the region of the walls perforated by small holes or slots. In the Accela-Cota and Hi-Coater, the flow of air through the tablet bed and out through the perforated wall of the pan. In the Driacoater air flow from the perforated pan wall through the tablet and in to the central region. The Glatt-Coater permits either co- or countercurrent air flow to suit particular products.

The film coating process can be carried in conventional pan, although operation variables such as speed of pan rotation, angle of pan axis, and temperature and humidity control may be more critical.¹⁴

Vector Corporation in a vector continuous pan coater, the inside of the pan is divided in to four zones: the first pre-heats the product to be coated, the next two apply the coating, and the last dries the coating and cools the product before discharge. A series of baffles-serving the same purpose as anti-slide bar in batch coating pan-run throughout the inside length of the coating pan.

Thomas Engineering the coating process proposed by Thomas Engineering has been used for coating large-volume OTC product. The pan employs different kinds of baffle arrangement compared with the vector equipment and the angle of the pan is not adjustable.

O’Hara technologies this is the most recently introduced coating equipment and shows certain processing features in common with the Vector Corporation and Thomas engineering coater, especially with regard to the design of integral baffle. The coating process is divided in to four air zones and six coating zones, which facilitate initial tablet warming, coating application and final drying.¹⁵

SUPERCELL™ Tablet Coater Revolutionary tablet coater that accurately deposits controlled amounts of coating materials on tablets, even if they are extremely hygroscopic or friable. Unique Features of SUPERCELL™ Coating Technology:

v Continuous coating

· Short processing time

· No scale-up parameters

v Flexible modular design

· R and D batch size (Minimum batch size of 30 grams)

· Production capacity of 6 cells coats 200,000 tablets per hour of 120 mg tablets

v Enhancing technology

· Difficult-to-coat shapes

· Friable tablets

· Multi-layer coating

v Enabling Technology

· "Low humidity process" suitable for moisture sensitive materials

· Accuracy of coating (RSD less than 1% demonstrated) ¹⁶

MICROENCAPSULATION TECHNIQUES:

Encapsulation of core ingredients into coating materials can be achieved by several methods. The selection of the microencapsulation process is governed by the properties (physical and chemical) of core and coating materials. Any kind of trigger can be used to prompt the release of the encapsulated ingredient, such as pH change (enteric and anti-enteric coating), mechanical stress, temperature, enzymatic activity, time, osmotic force, etc.

Table 4: Various microencapsulation techniques and the processes involved in each technique

No Microencapsulation technique

Major steps in encapsulation

1 Spray-drying

a. Preparation of the dispersion

b. Homogenization of the dispersion

c. Atomization of the infeed dispersion

d. Dehydration of the atomized particles

2 Spray-cooling

a. Preparation of the dispersion

b. Homogenization of the dispersion

c. Atomization of the infeed dispersion

3 Spray-chilling

a. Preparation of the dispersion

b. Homogenization of the dispersion

c. Atomization of the infeed dispersion

4 Fluidized-bed coating

a. Preparation of coating solution

b. Fluidization of core particles.

c. Coating of core particles

5 Extrusion

a. Preparation of molten coating solution

b.Dispersion of core into moltenpolymer

c. Cooling or passing of core-coat

mixture through dehydrating liquid

6 Centrifugal extrusion

a. Preparation of core solution

b. Preparation of coating material solution

c. Co-extrusion of core and coat solution

through nozzles

7 Lyophilization

a. Mixing of core in a coating solution

b. Freeze-drying of the mixture

8 Coacervation

a. Formation of a three-immiscible

chemical phases

b. Deposition of the coating

c. Solidification of the coating

9 Centrifugal suspension

a. Mixing of core in a coating material

b. Pour the mixture over a rotating disc to obtain encapsulated tiny particles

c. Drying

10 Cocrystallization

a. Preparation of supersaturated sucrose

solution

b. Adding of core into supersaturated

solution

c. Emission of substantial heat after

solution reaches the sucrose

crystallization temperature

11 Liposome entrapment

a. Microfluidization

b. Ultrasonication

c. Reverse-phase evaporation

12 Inclusion complexation

Preparation of complexes by mixing or

grinding or spray-drying

COATING SYSTEMS:

Enteric coating liquid An aqueous enteric coating liquid having a good dispersion stability and a good resistance to gastric juice comprising an alkali metal salt of an acid having a acid dissociation constant of at least 3 at 25° C. and a water-insoluble oxycarboxylic acid type cellulose derivative dispersed in water or a mixture of water and at most 20% by weight of a lower alcohol. The enteric coating liquid has been prepared generally by dissolving in an organic solvent a high molecular substance which is insoluble in water and gastric juice, but soluble in intestinal juice. However, the enteric coating according to such a process is economically disadvantageous, because a large quantity of an organic solvent is required in the preparation of the coating liquid and also the recovery of the solvent is difficult.¹⁸

Table 5: Formulation variables of the inner coat of the double-coating

Concentration of organic acids (%)*		pH of the inner coating solutions
Without organic acid		5.6
Adipic acid	10 15 20	5.6 5.6 5.6
Citric acid	10 15 20	5.6, 5.8, 6.0 5.6 5.6

*The concentrations of the organic acid were based on the dry weight of the polymer.⁴

Coating in Fluidized Beds the basic principle underlying their operation is to suspend the tablet in an upward moving stream of air so that they are no longer in contact with one another. An atomizer introduces spray solution into the stream and onto the tablets, which are then carried away from the spraying region where the coating is dried by the fluidized air. An atomizer introduces spray solution into the stream and onto the tablet, which are then carried away from the spraying region where the coating is dried by the fluidized air.

Compression coating a method has been described for compression a coating around a tablet “core” using specially designed presses. The process involves preliminary compression of the core formulation to give a relatively soft tablet, which is then transferred to a large die already containing some of the coating material. After centralizing the core, further coating granulation is added and the hole compressed to form the final product. From a formulation point of view, this requires a core material that develops reasonable strength at low compressional load and a coating material in the form of fine free-flowing granules with good binding quality.

Layered tablets in search for novelty as much as functionality, tablets have been produced on presses capable of compressing a second layer on top of original material. Indeed, the standard double-rotary machines require little modification in order to achieve this goal. Such tableting procedures facilitate the co-formulation of incompatible materials and design of complex release pattern, as well as adding a new dimension to ease of identification. Several high-output tablet presses design to produce two or three- layered tablets are commercially available.¹⁴

Enteric-coated systems: Enteric coatings have traditionally been used to prevent the release of a drug in the stomach. Enteric coatings are pH sensitive. Generally, enteric-coated polymers protect a dosage form the acidic environment of the stomach and allow drug delivery to the small or large intestine, depending on their dissolution pH and the thickness of the coating applied. Although enteric-coated formulations are used mainly in connection with site-specific delivery such formulations can be utilized in time-controlled drug administration, when a lag time is needed

Figure1:Schematic representation of the Enteric-coated system.

Chronotropic® system consists of a core containing drug reservoir coated by a hydrophilic polymer. The enteric-coated film is given outside this layer to overcome intra-subject variability in gastric emptying rates. The lag time and the onset of action are controlled by the thickness and the viscosity grade of polymer.

Pulsincap systems: The Pulsincap® system was developed by R. P. Scherer International Corporation, Michigan, US, and is one of such system that comprises of a water-insoluble capsule body enclosing the drug reservoir.

Figure 3: Different stages in drug release from Pulsincap.

The body is closed at the open end with a swellable hydrogel plug.The plug material consists of insoluble but permeable and swellable polymers (eg, polymethacrylates), erodible compressed polymers (eg, hydroxypropylmethyl cellulose, polyvinyl alcohol, polyvinyl acetate, polyethylene oxide), congealed melted polymers (eg, saturated polyglycolated glycerides, glyceryl monooleate), and enzymatically controlled erodible polymer (eg, pectin). When this capsule came in contact with the dissolution fluid, it swelled; and after a lag time, the plug pushed itself outside the capsule and rapidly released the drug. The dimension or length of the plug and its point or position of insertion into the capsule controlled the lag time.¹⁹

Double-coating system:

The rationale for the double-coating design stems from the fact that the dissolution of an enteric polymer depends on the ionisation of its carboxylic acid groups at elevated pH. It is therefore conceivable that if some of the acid groups are neutralised to their ionised form (salt), the dissolution rate of the polymer would be increased. However, the inevitable preexposure to acidic medium for enteric coatings would transform the polymer salt back into its original acid form. It was hypothesized that the functionality of the neutralized film coating could be protected in acidic medium by over coating with a conventional enteric layer: the novel double-coating concept (Fig). An organic acid was introduced to the neutralized inner layer to further accelerate dissolution by the formation of salt and so generating a buffer system.

Fig. Schematic of the double-coating concept.

Single coating: The recommended coating level to achieve enteric properties on tablets is in the range of 4–6 mg polymer (pure polymer) per cm² surface area of the core. The tablets were coated using Strea-1 bottom spray fluidized bed spray coater (Aeromatic AG, Bubendorf, Switzerland). The coating conditions were: inlet air temperature 40 °C, outlet air temperature 30 °C, fan capacity 15 (equivalent to air flow 150 m3/h), atomising pressure 0.2 bar and spray rate 2.0 ml/min. After coating, the tablets were further fluidised for 15 min in the coater and cured in an oven at 40 °C for 2 h.

Double-coating:

Inner coat- The formulation variables of the inner coat of the double-coating are summarised in Table 1. the single coating the amount of polymer applied on the inner coatswas 5 mg/cm2. The coating conditions for the inner coating formulations were the same as the single coating except lower spray rate (1.0 ml/min) was applied. After coating, the tablets were further fluidised for 15 min in the coater and subjected to the outer coating process.

Outer coat- The outer coat of the double-coating was identical to the single coating. The coating level was also 5 mg/cm2 polymer. After applying the outer coat, the tablets were further fluidised for 15 min in the coater and cured in an oven at 40 °C for 2 h.

Electrostatic powder coating system:

Another technology relating to the design and operation of dry powder electrostatic tablet coaters and the development of coating materials has emerged from Phoqus Pharmaceutical Technologies (Goudhurt, UK). The electro photographic process contains six steps. In the first step, a corona discharge caused by air breakdown charges the surface of a photoreceptor acting as an insulator. Light, reflected from the image or produced by a laser, then discharges the normally insulating photoreceptor, producing a latent image. In the third step, electrostatically charged and pigmented polymer particles called toner and approximately 10 microns in diameter are brought into the vicinity of the latent image. By virtue of the electrical field created by the charges on the photoreceptor, the toner adheres to the latent image, transforming it into a real image. Next, the developed toner on the photoreceptor is transferred to paper by corona charging the back of the paper with a charge that is the opposite to that of the toner particles. In the fifth step, the image is permanently fixed to the paper by melting the toner into the paper surface. Finally, the photoreceptor is discharged and cleaned of any excess toner using coronas, brushes and scrappers and/or blades.²⁰

Film coating are applied to pharmaceutical dosage form to protect them against the environment, to improve their appearance, to mask undesirable test or odor, to impart enteric properties and to modulate release of medicaments.²¹ Aqueous enteric film coatings have been used widely in recent years.²² Polymeric film coatings are frequently used to control drug release from solid pharmaceutical dosage forms. Several natural and synthetic macro molecules have proven to be suitable coating materials, providing different types of drug release behavior, e.g. zero-order kinetics, pulsatile and sigmoidal patterns.²³

Coating defects:

Here is a list of common defects associated with coated tablets and some likely causes.

Picking and sticking: This is when the coating removes a piece of the tablet from the core. It is caused by over-wetting the tablets, by under-drying, or by poor tablet quality.

Bridging: This occurs when the coating fills in the lettering or logo on the tablet and is typically caused by improper application of the solution, poor design of the tablet embossing, high coating viscosity, high percentage of solids in the solution, or improper atomization pressure.

Capping: This is when the tablet separates in laminar fashion. The problem stems from improper tablet compression, but it may not reveal itself until you start coating. How you operate the coating system, however, can exacerbate the problem. Be careful not to over-dry the tablets in the preheating stage. That can make the tablets brittle and promote capping.

Erosion: This can be the result of soft tablets, an over-wetted tablet surface, inadequate drying, or lack of tablet surface strength.

Twinning: This is the term for two tablets that stick together, and it’s a common problem with capsule shaped tablets. Assuming you don’t wish to change the tablet shape, you can solve this problem by balancing the pan speed and spray rate. Try reducing the spray rate or increasing the pan speed. In some cases, it is necessary to modify the design ofthe tooling by very slightly changing the radius. The change is almost impossible to see, but it prevents the twinning problem.

Peeling and frosting: This is a defect where the coating peels away from the tablet surface in a sheet. Peeling indicates that the coating solution did not lock into the tablet surface. This could be due to a defect in the coating solution, over-wetting, or high moisture content in the tablet core.

Chipping: This is the result of high pan speed, a friable tablet core, or a coating solution that lacks a good plasticizer.

Mottled color: This can happen when the coating solution is improperly prepared, the actual spray rate differs from the target rate, the tablet cores are cold, or the drying rate is out of spec.

Orange peel: This refers to a coating texture that resembles the surface of an orange. It is usually the result of high atomization pressure in combination with spray rates that are too high.¹³

REFERENCES:

1) Bendas E.R., and Ayres, J.W., Leaky enteric coating on ranitidine hydrochloride beads: Dissolution and prediction of plasma data,European Journal of Pharmaceutics and Biopharmaceutics. 2008; 69: 977–985.

2) Aleksandra D., Thomas D.B., Jean P.R., Willy B., Paul F. and Chris V., In-vitro and in-vivo evaluation of enteric-coated starch-based pellets prepared via extrusion/spheronisation. European Journal of Pharmaceutics and Biopharmaceutics. 2008; 70: 302–312.

3) Remington, the science and practice of pharmacy, B.I. publications PVT. LTD. 21^st edition, volume-1, 932.

4) Fang L., Rosario L., Christian M., Hans-Ulrich P., Peter B. and Abdul W. B., A novel concept in enteric coating: A double-coating system providing rapid drug release in the proximal small intestine, Journal of Controlled Release. 2009; 133: 119–124.

5) Lachman L., Lieberman A.H. and Kanig J.L., The Theory and Practice of Industrial Pharmacy, Varghese publishing house, Third edition, 366.

6) Brahmankar D.M. and Jaiswal S.B., Biopharmaceutics and Pharmacokinetics a treatise, Vallabh Prakation, 337.

7) Rathbone M.J., Hadgraft J. And Roberts M. S., Modified release drug delivery technology Marcel Dekker, Inc., 2003, 224-229.

8) Mirja R., Studies on Aqueous Film Coating of tablets Performed in A Side-Vented Pan Coater, Pharmaceutical Technology Division Department of Pharmacy University of Helsinki, Finland. 2003.

9) Niazi, Handbook of pharmaceutical manufacturing formulation, CRC Press LLC, vol-1, 2004, 267-288.

10) Vyas S.P., and Khar R.K., Controlled Drug Delivery concept and advances, Vallabh prakashan, first edition 2002, 167-168.

11) Lu Xu, Sanming Li, and Hisakazu S., Preparation and evaluation in vitro and in vivo of captopril, elementary osmotic pump tablets. Asian Journal of Pharmaceutical Sciences. 2006; 1 (3-4): 236-245.

12) Dow Chemical Company, METHOCEL Cellulose Ethers in Aqueous Systems for Tablet Coating, Form No. 198-00755-0702 AMS, Published July 2002

13) Michael D. T., Tablet coating, Copyright, CSC Publishing. Tablets and Capsules.

14) Banker G.S., and Rhodes C.T., Modern Pharmaceutics Fourth Edition, Revised and Expanded. 326-327.

15) Thakral N.K., continuous tablet coater: Developments, Advantages and Limitation, innovation in pharmaceutical technology,

16) Dr. Sahoo P.K., Tablets, Pharmaceutical Technology, Delhi, Institute of Pharmaceutical Sciences and Research Pusph Vihar-III, M.B.Road, New Delhi-110017, 04-10-2007

17) Kashappa G.H., Desai and Hyun J.P., Recent Developments in Microencapsulation of Food Ingredients, Drying Technology. 2005; 23: 1361–1394.

18) Mukohyama, Enteric coating liquid, United States Patent 4606771, Application Number: 06/645728, Publication Date: 08/19/1986.

19) Patel G.C., Specialized chronotherapeutic drug delivery systems, Vol. 5, Issue 1, www.Pharmainfo.net, 2007.

20) Sastry S.V., Nyshadham J.R. and Joseph A.F., Recent technological advances in oral drug delivery – a review, PSTT Vol. 3, No. 4 April 2000.

21) Rane1 S. and Kale V., Evaluation of modified Guar Gum as film coating material, International Journal of Chem Tech Research. Vol.1, No.2, April-June 2009; 180-182.

22) Hashmat D., Shoaib M.H., Mehmood Z.A., Bushra R., Yousuf R., and Lakhani F., Development of Enteric Coated Flurbiprofen Tablets using Opadry/acryl-eze System—A Technical Note, AAPS PharmSciTech, Vol. 9, No. 1, March 2008.

23) Lecomte F., Siepmann J., Walther M., MacRae R.J., and Bodmeier R., B lends of enteric and GIT-insoluble polymers used for film coating: physicochemical characterization and drug release patterns, Journal of Controlled Release. 2003; 89: 457–471.

Received on 11.01.2010 Modified on 24.02.2010

Research J. Pharm. and Tech.3 (3): July-Sept. 2010; Page 665-671