FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
"A NOVEL CONTROLLED-RELEASE ORAL COMPOSITION OF
ALBENDAZOLE"
2. APPLICANT:
(a)NAME:FDC LTD.
(b)NATIONALITY: Indian Company incorporated under the Companies Act, 1956
(c) ADDRESS: 142-48, S.V. Road, Jogeshwari (West), Mumbai - 400 102, Maharashtra, India
3.PREAMBLE TO THE DESCRIPTION:
The following specification particularly describes the invention and the manner in which it is to be performed.

Technical field:
The present invention relates to a novel controlled-release solid oral pharmaceutical composition of Albendazole, comprising a combination of gastroretentive drug delivery system (GRDDS) and an enteric drug delivery system for effective treatment of luminal nematodes and systemic helminthiasis.
Background and prior art:
Albendazole is a broad spectrum benzimidazole anthelmentic, widely used in human and veterinary helminth infections. It is the first line treatment for nematodes such as ascaris, enterobius, trichuris, strongyloides and hookworms that are prevalent in India, and for systemic cestode infections such as neurocysticercosis and hydatid disease.
Albendazole is a BCS class II molecule i.e. a low solubility and high permeability molecule. It has pH-dependent solubility, showing poor and erratic solubility in gastrointestinal tract (GIT), and hence exhibiting extremely low bioavailability. However, it shows enhanced solubility in strong acids and bases.
Conventional Albendazole formulations are available in the form of film-coated tablets and suspensions. Oral liquid formulations of Albendazole such as suspensions and nanosuspensions, get solubilized in gastric pH, and readily absorbed in duodenum and jejunum. Although the drug has complete solubility and permeability with specialized formulations such as nanosuspension and solid dispersion, the bioavailabilty of these formulations have been hampered by extensive first-pass effect of the drug. First pass effect is a phenomenon of drug metabolism whereby the concentration of drug is greatly reduced during the absorption process related to liver and gut wall, before reaching systemic circulation in a patient.
Solublization of Albendazole doesn't necessarily improve the bioavailabilty and hence the solublization technology alone will not be sufficient to improve the therapeutic efficacy. On the other hand, delaying the drug release from stomach to intestine, may reduce the extent of drug reaching to the liver via portal circulation and hence improve

the drug availability in intestinal mucosa and lumen. However, the poor solubility of Albendazole in intestinal pH may be the hurdle to develop enteric release formulation.
Albendazole undergoes extensive first-pass metabolism (i.e. first-pass effect) in the liver and gut wall, resulting in pharmacologically-active sulfoxide metabolite in plasma, which then shows the intended anthelmenthic activity. However, Albendazole sulfoxide (ABZSO) is comparatively less permeable and potent than the parent drug 'Albendazole'. The helminths absorb the drug via passive diffusion through surface rather than via sucked blood. Hence, presence of luminal Albendazole solution is more desirable than high plasma concentration of ABZSO, for the treatment of intestinal parasites. Systemic ABZSO is secreted in intestinal lumen by active transport at a rate of about 0.165 ± 0.05 nmol/cm, and this secretion renders very small amount of available ABZSO in intestinal lumen, resulting in low therapeutic efficacy against intestinal helminthes. Further, ABZSO exhibits enantiomerism, and only (+) enantiomer of ABZSO is active in humans. Hence, first-pass metabolism reduces Albendazole potency by 50%.
CN 101288659 discloses a gastric floating pellet composed of a core, a drug layer, an isolation layer, a sustained-release layer and a protective layer, and having a density less than 1 g/cm3. The drug layer consists of drugs such as albendazole, and coating materials. The pellet is packaged in capsules to obtain a gastric floating capsule.
CN 101007170 discloses a process for preparation of sustained-release formulation for treating hydatidosis, comprising at least one active ingredient including albendazole, and a biocompatible material including biodegradable and/or non-biodegradable materials.
IN 2004MU01360 discloses a modified release dosage form for low dose active ingredient targeted to be delivered in the proximal part of the gastrointestinal tract, wherein the dosage form is an inlay tablet comprising an inner portion made of pharmaceutically active ingredient such as albendazole, release controlling agent(s) and pharmaceutically acceptable excipients, and an outer portion including hydrophobic nonbiodegradable material(s), water soluble diluent(s) and other pharmaceutically acceptable excipients. The application is related to the formation of tablet in tablet for controlled release of active pharmaceutical ingredients. The dosage form is fabricated using

hydrophobic polymers, which are not suitable for delivery of poorly soluble drugs. The application fails to describe the intestinal delivery of the drug using enteric polymer. Intestinal drug concentration is equally important to achieve the desired therapeutic activity against intestinal worms.
WO 2007036671 discloses microparticulate systems with modified release of oral active ingredient(s); where the multimicroparticulate galenic system operates in accordance with a dual time-dependent and pH-dependent release mechanism.
WO 2009150514 discloses a process for making oral solid gastro-retentive forms, comprising the steps of providing a powder mixture comprising an active ingredient such as albendazole and a hydrophobic powder, over-granulating the powder mixture with a granulating solution, into an overgranulated paste, and drying the paste into a solid as well as to pharmaceutical solid dosage forms which are retained in the stomach or upper gastrointestinal tract for a controlled delivery of a drug. The process disclosed in the application is a lengthy, tedious process and very difficult to adopt for large scale manufacturing.
WO 2006044202 discloses enteric coated pharmaceutical composition comprising at least one active ingredient in a core, and an enteric coating on the core, where the enteric coating comprises a gastric fluid channeling agent which allows the rapid drug release from the core in intestinal region. The composition in the application does not describe gastroretentive dosage form that offers favorable pH for the drug dissolution and better bioavailability.
Although conventional film-coated tablets prevent Albendazole solublization in stomach, and ensure the drug release in the intestine by using enteric polymers in coating material, the zwitterion nature of Albendazole showing iso-electric point of 6-6.5, retards the drug solublization in intestinal pH and results in low therapeutic efficacy of the drug.
In the conventional film-coated tablet of Albendazole, once the coat is dissolved, the whole drug is dumped in the intestine. Due to low solubility of the drug and high viscosity of bowel content, only a small fraction of drug gets dissolved and penetrates the

helminth surface, and even smaller amount of drug gets systemically absorbed. This proves to be a major drawback of conventional enteric release tablets for their use against intestinal as well as systemic helminthes.
There are a number of prior arts which disclose controlled-release dosage form of Albendazole, but none of them teach a composition that has equally high efficacy against luminal nematodes and systemic helminthiasis.
Thus, there is a need to develop a novel controlled-release oral dosage form of Albendazole that has equally high efficacy against luminal nematodes and systemic helminthiasis.
Object of invention:
Accordingly, the main objective of the present invention is to provide a controlled-release oral dosage form of Albendazole comprising a novel combination of gastroretentive and enteric release delivery systems for improved pharmacokinetic and pharmacodynamic profile.
Another objective of the present invention is to provide a controlled-release oral dosage form of Albendazole having improved systemic bioavailability and enhanced luminal availability, with equally high efficacy against luminal nematodes and systemic helminthiasis.
Yet another objective of the present invention is to provide a controlled-release oral dosage form of Albendazole, which not only exhibits improved therapeutic efficacy against luminal and systemic helminthiasis, but also alleviates the chances of dose dumping and consequent adverse drug reactions.
Summary:
In accordance with the above objectives, the present invention describes a novel controlled-release solid oral dosage form of Albendazole, comprising a gastroretentive

release part and an enteric release part. This novel combination of gastroretentive and enteric release of Albendazole, provides both improved systemic bioavailability and enhanced luminal availability.
The gastroretentive part provides a gastroretentive drug delivery system (GRDDS); and the enteric part provides an enteric drug delivery system.
The gastroretentive part comprises Albendazole, rate-controlling hydrophilic polymers, a gas generating agent, superdisintegrants and at least one pharmaceutically acceptable excipient. The enteric part comprises Albendazole, a microenvironmental pH modifier, an enteric coating polymer, superdisintegrants and at least one pharmaceutically acceptable excipient.
Detailed description of the invention:
The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.
The present invention describes a novel controlled-release solid oral dosage form of Albendazole comprising a gastroretentive release part and an enteric release part. This novel combination of gastroretentive and enteric release of Albendazole, provides improved systemic bioavailability and enhanced luminal availability.
The gastroretentive release part provides a gastroretentive drug delivery system (GRDDS); and the enteric release part provides an enteric drug delivery system. The GRDDS provides improved dissolution of albendazole due to highly acidic pH of stomach, and thus increases systemic bioavailability of the drug. However, due to the poor solubility of Albendazole in intestinal pH it is difficult to develop enteric release layer. To overcome such difficulties, the present invention discloses microenvironmental pH adjustment as the "best suitable technique to improve the drug solubility, by use of a microenvironmental pH modifier. Hence, the enteric release part with the microenvironmental pH modifier, enhances drug dissolution in intestinal lumen and acts

locally against luminal helminth infections. In addition to microenvironmental pH modifier, surfactants and solubilizers are also used to improve the solubility of Albendazole.
Thus, the Albendazole formulation of the present invention provides gastroretentive drug delivery system as well as enteric drug delivery system with microenvironmental pH adjustment. The gastroretentive controlled drug delivery system ensures complete solublization of Albendazole in stomach, and efficient absorption of Albendazole in duodenum and jejunum, thus improving systemic bioavailability of Albendazole. The enteric immediate-release drug delivery system with microenvironmental pH adjustment and solubilizer, improves solubilization of Albendazole in intestine, and thus provides improved luminal availability of Albendazole in solution form.
The gastroretentive part of the present invention, comprises Albendazole, rate-controlling hydrophilic polymers, a gas-generating agent, superdisintegrants and at least one pharmaceutically acceptable excipient.
Hydrophillic polymers are a network of polymeric chains that are water-insoluble, and sometimes found as a colloidal gel, wherein water is the dispersion medium. Hydrophillic polymers are swellable when incorporated in solid dosage forms, and creates a rigid gel structure in presence of dissolution media. This rigid gel structure provides rate controlling barrier for drug release and drug dissolution. Hydrophilic polymers are derived from natural, semisynthetic and synthetic sources.
The hydrophillic polymers used in the present invention are selected from the group consisting of cellulose, cellulose derivatives comprising hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose, cellulose esters, natural gums, polyvinylpyrrolidone, polyvinyl alcohol and poly(ethylene oxide), in the range of 3% to 40% w/w of total composition.
Gas generating agent is used in the formulation to increase porosity, which further improves drug release profile. Gas generating agents increase the channels and hence it assures maximum drug release from matrix, especially for poorly soluble drugs.

Moreover, gas generating agents reduce the density of the dosage form and thus offer prolonged floating and gastroretention.
The gas generating agent used in the present invention, is selected from carbonates or bicarbonates more preferably sodium carbonate, sodium bicarbonate, magnesium carbonate, calcium carbonate, aluminum carbonate and zinc carbonate; in the range of 0.1% to 10% w/w of total composition.
The enteric part of the present invention comprises Albendazole, a microenvironmental pH modifier, an enteric coating polymer, superdisintegrants and at least one pharmaceutically acceptable excipient.
The microenvironmental pH modifier used in the present invention is selected from but not limited to succinic acid, malic acid, fumaric acid, ascorbic acid, citric acid and tartaric acid, in the range of 0.1% to 8% w/w of total composition.
The enteric coating polymer used in the present invention is selected from a group consisting of but not limited to acrylates, cellulose acetate phthalate, hydroxypropyl methylcellulose (HPMC) phthalate, cellulose actetate trimellitate, polyvinyl acetate phthalate, HPMC acetate succinate, carboxymethylcellulose, alginic acid, alginate salts and shellac; in the range of 3.0 % to 30 % w/w of total composition.
Superdisintegrants used in the formulation, increase the swellability of the dosage form, and offer increased size of dosage form that is not affected by gastric emptying. In addition, superdisintegrants increase the wettability of dosage forms which allows penetration of gastric fluid inside the dosage form. The intimate contact of gastric fluid with hydrophilic polymer, increases the gel strength of the matrix and hence offers controlled mode of drug release from the dosage forms.
Superdisintegrants are used because of their high absorption properties. The formulation containing superdisintegrants swell in presence of gastric fluid and hence create high pressure within the tablet matrix, which favors for faster disintegration of tablets. However, the present invention describes the role of superdisintegrants, which absorb

high quantity of gastric fluids and hence offer aqueous environment for matrix system. Gastric fluid is absorbed by the superdisintegrants that lead to gellation of hydrophillic polymer, and form a viscous gel layer. The formed gel layer maintains the integrity of the tablet dosage form and acts as a barrier for drug release.
The superdisintegrants used for gastroretentive part as well as enteric coating part, are selected from but not restricted to crospovidone, croscarmellose sodium and sodium starch glycolate; in the range of 0.5 % to 10 % w/w of total composition.
The pharmaceutically acceptable excipients used for gastroretentive as well as enteric coating part, are selected from a group consisting of surfactant, solublizers, diluent, binder, filler, glidant, lubricant and buffer.
The solubilizers and surfactants used in the present invention are selected from but not limited to sodium lauryl sulphate, polyoxy esters, fatty acid esters, fatty acid alcohols, polyoxyethylene stearate, poloxamer, polyethylene glycol esters, polyethylene glycol glycerides, propylene glycol esters, propylene glycol glycerides, sorbiton monoesters and polyoxyethylene sorbiton monoesters; in the range of 0.05% to 20% w/w of total composition.
The Albendazole formulation of the present invention being a controlled release formulation, entirely alleviates the chances of dose dumping phenomena commonly seen with the conventional film coated tablets, and consequently alleviates adverse drug reactions such as gastrointestinal disturbances, rashes and alopecia. As a result, the Albendazole formulation of the present invention provides improved systemic bioavailability, enhanced luminal availability, improved therapeutic efficacy against luminal and systemic helminthiasis, and reduced adverse drug reactions.
The dosage form of the present invention encompasses solid oral dosage forms like bilayer tablet, tablet in tablet, tablet in capsule, pellets in capsule and powders in capsule.
The present invention is exemplified by the following examples which are provided for illustration only and should not be construed to limit the scope of the invention

The amount of Albendazole included in gastroretentive layer ranges from 100 mg to 300 mg and the enteric layer consists of 100 - 300 mg
EXAMPLES:
Example 1:
400 mg Albendazole Bilayer Tablet

Sr.
No. Ingredient mg/tablet
Gastroretentive drug delivery system (GRDDS) part
1. Albendazole 200 mg
2. Hydroxypropylmethylcellulose 45 mg
3. Sodium Starch Glycolate 6mg
4. Sodium bicarbonate 3mg
5. Magnesium stearate 1.5 mg
6. Colloidal silicon dioxide 3mg
7. Lactose 25.5 mg
Enteric drug delivery system part
8. Albendazole 200 mg
9. Microcrystalline cellulose 16.5 mg
10. Methyl acrylate 48 mg
11. Sodium Starch Glycolate 12 mg
12. Magnesium stearate 1.5 mg
13. Colloidal silicon dioxide 3mg
14. Fumaric acid 15 mg
Total 580 mg
Process: GRDDS part: Albendazole, hydroxypropylmethylcellulose, sodium starch glycolate, sodium bicarbonate and lactose were dry blended. The blend was granulated with granulating fluid, water: isopropyl alcohol (50:50). The granules were lubricated with colloidal silicon dioxide and magnesium stearate.

Enteric part: Albendazole, microcrystalline cellulose, sodium starch glycolate and fumaric acid, were dry blended. The blend was granulated with aqueous suspension of methyl acrylate. The granules were lubricated with colloidal silicon dioxide and magnesium stearate.
The above blend is compressed in two layers using 16.5x8 mm capsule shaped punches to obtain Bilayer tablets.
The formulation prepared as above is further subjected to dissolution studies and accelerated degradation studies to assess the drug release profile as well as the stability of the formulation over a period of time. The details of the same are presented below.
In order to discriminate the release profile of two different compartments from the single unit solid dosage form of Albendazole, two different dissolution media were developed and studied.
Drug release profile 1 (discriminatory to gastroretentive release)
• Albendazole has low aqueous solubility and hence the dissolution is incomplete in the pH range of 1.2 -7.4
• In order to improve the saturation solubility and maintain sink condition 0.5% w/v of Polysorbate 80 was added in the dissolution media of 0.1 N HC1 and the pH of 1.2 was maintained
• When compared with conventional immediate release formulation, which shows more than 90% of drug release within 60 min, the formulation of the present invention shows the drug release profile over the period of 12 h.
• Moreover, 58% of drug release within 2 h is due to the surfactant properties of polysorbate and hence this media does not show the enteric release profile
Drug release profile 2 (discriminatory to enteric release)
• In order to prove the acid resistant nature of the formulation of present invention,
0.1 N HC1 adjusted to pH 1.2 is used as a dissolution media.

• Drug dissolution studies using 0.1 N HC1 as media show that more than 60 % of drug refease from conventional immediate refease dosage form, whereas /ess than 20% drug release from the dosage form of the present invention.
Drug Release Profile 1 (discriminatory to gastroretentive releases-Dissolution media: 0.1N HC1 with 0.5% Polysorbate 80

Sr.No Time Points % Drug Release
1 1Hr 58

2 2Hr 64

3 4Hr 71

4 6Hr 75

5 8Hr 83

6 12 Hr 94

Drug Release Profile 2 (discriminatory to enteric release): Dissolution media: 0.1N HCI
Sr.No Time Points % Drug Release
1 1Hr 17

2 2Hr 26

3 4Hr 39

4 6Hr 49

5 8Hr 57

Stability Data:
["Stability Condition Stability
Station | Description % Assay
Initial Pink Colored Capsule Shaped Film Coated Tablet 100.2
40 ±2°C/ 75±5%RH 1M Complies 100.0

2M Complies 99.7

3M Complies 99.7

6M Complies 98.9
30±2°C/65±5%RH 3M Complies 100.1

6M Complies 99.2
25±2°C/60±5%RH 3M Complies 99.9

6M Complies 99.6
Dissolutio n Profile of s tability Batch (disc riminatory to gastroretentive re ease):

Stability Stability
Station % Drug release
Condition
1 Hr 2Hr 4Hr 6Hr 8hr 12 hr
Initial 58 64 71 75 83 94
40±2°C/ 75±5%RH 1M 58 63 70 77 80 95

2M 56 65 69 75 81 92

3M 61 64 68 76 79 90

6M 56 63 66 77 82 93
30 ±2°C/ 65±5%RH 3M 57 61 69 79 82 94

6M 55 60 66 78 81 96
25±2°C/ 60±5%RH 3M 58 63 65 74 83 92

6M 54 61 70 78 86 96
Example 2:
400 mg Albendazole Pellets in Capsules
Sr.
No. Ingredient mg/tablet
Gastroretentive drug delivery system (GRD DS) part

1. Albendazole 200 mg

2. Hydroxyethylcellulose 45 mg

3. Crosscarmellose sodium 6mg

4. Sodium carbonate 3mg

5. Magnesium stearate 1.5 mg

6. Colloidal silicon dioxide 3mg

7. Microcrystalline cellulose 5.5 mg

Enteric drug delivery system part

8. Albendazole 200 mg

9. Microcrystalline cellulose 16.5 mg

10. Hydroxypropylmethylcellulose acetate succinate 48 mg

11. Crospovidone 12 mg

12. Magnesium stearate 1.5 mg

13. Colloidal silicon dioxide 3mg

14. Tartaric acid 15 mg

Total 560 mg


Process: GRDDS part: Albendazole, hydroxyethylcellulose, croscarmellose sodium, sodium carbonate and lactose were dry blended. The blend was granulated with granulating fluid, water: isopropyl alcohol (75:25). The granules were lubricated with colloidal silicon dioxide and Microcrystalline cellulose and compressed into pellets. Enteric part: Albendazole, microcrystalline cellulose, crospovidone and tartaric acid was dry blended. The blend was granulated with aqueous suspension of Hydroxypropylmethylcellulose acetate succinate. The granules were lubricated with colloidal silicon dioxide and magnesium stearate and compressed into pellets. GRDDS and enteric pellets were filled in capsules.

Example 3:
400 mg Albendazole Tablets in Capsule
Sr.
No. Ingredient mg/tablet
Gastroretentive drug delivery system (GRD DS) part
1. Albendazole 200 mg
2. Hydroxyethylcellulose 45 mg
3. Croscarmellose sodium 6mg
4. Sodium carbonate 3mg
5. Magnesium stearate 1.5 mg
6. Colloidal silicon dioxide 3mg
7. Lactose 16.5 mg
Enteric drug delivery system part
8. Albendazole 200 mg
9. Lactose 45.5 mg
10. Methyl acrylate 48 mg
11. Sodium Starch Glycolate 12 mg
12. Magnesium stearate 1.5 mg
13. Colloidal silicon dioxide 3mg
14. Succinic acid 15 mg
Total 600 mg

Process: GRDDS part: Albendazole, hydroxyethylcellulose, croscarmellose sodium, sodium carbonate and lactose were dry blended. The blend was granulated with granulating fluid, water: isopropyl alcohol (75:25). The granules were lubricated with colloidal silicon dioxide and magnesium stearate and compressed into minitablets. Enteric part: Albendazole, lactose, sodium starch glycolate and succinic acid was dry blended. The blend was granulated with aqueous suspension of methyl acrylate. The granules were lubricated with colloidal silicon dioxide and magnesium stearate and compressed into minitablets. GRDDS and enteric minitablets were filled in capsules.

Example 4:
400 mg Albendazole bilayer tablet.
Sr.
No. Ingredient mg/tablet
Gastroretentive drug delivery system (GRD DS) part
1. Albendazole 200 mg
2. Carbopol 45 mg
3. Sodium Starch Glycolate 6mg
4. Calcium carbonate 3mg
5. Magnesium stearate 1.5 mg
6. Colloidal silicon dioxide 3mg
7. Lactose 16.5 mg
Enteric drug delivery system part
8. Albendazole 200 mg
9. Microcrystalline cellulose 16.5 mg
10. Polyvinyl acetate phthalate 57 mg
11. Sodium Starch Glycolate 12 mg
12. Calcium stearate 1.5 mg
13. Colloidal silicon dioxide 3mg
14. Malic acid 15 mg
Total 580 mg

Process: GRDDS part: Albendazole, carbopol, sodium starch glycolate, calcium
carbonate and lactose were dry blended. The blend was granulated with granulating fluid,
water: isopropyl alcohol (50:50). The granules were lubricated with colloidal silicon
dioxide and magnesium stearate.
Enteric part: Albendazole, microcrystalline cellulose, sodium starch glycolate and malic
acid, were dry blended. The blend was granulated with aqueous suspension of Polyvinyl
acetate phthalate. The granules were lubricated with colloidal silicon dioxide and calcium
stearate.
The above blend is compressed in two layers using capsule 16.5x8 mm capsule shaped
punches to obtain Bilayer tablets.
Example 5:

400 mg Albendazole Bilayer Tablet
Sr. no. Ingredient mg/tablet
Gastroretentive drug delivery system (GR DDS) part
1. Albendazole 100 mg
2. Hydroxypropylmethylcellulose 45 mg
3. Sodium Starch Glycolate 6mg
4. Sodium Bicarbonate 3mg
5. Magnesium stearate 1.5 mg
6. Colloidal silicon dioxide 3mg
7. Lactose 25 mg
Enteric drug delivery system part
8. Albendazole 300 mg
9. Sodium Starch Glycolate 12 mg
10. Magnesium stearate 1.5 mg
11. Colloidal silicon dioxide 3mg
12. Microcrystalline Cellulose 17.00 mg

13. Eudragit 33 mg
14. Fumaric acid 15 mg
Total 565 mg
Process: GRDDS part: Albendazole, hydroxypropylmethylcellulose, sodium starch glycolate, sodium bicarbonate and lactose were dry blended. The blend was granulated with granulating fluid, water; isopropyl alcohol (50:50). The granules were lubricated with colloidal silicon dioxide and magnesium stearate.
Enteric part: Albendazole, microcrystalline cellulose, sodium starch glycolate and fumaric acid, were dry blended. The blend was granulated with aqueous suspension of eudragit. The granules were lubricated with colloidal silicon dioxide and magnesium stearate.
The above blend is compressed in two layers using capsule 16.5x8 mm capsule shaped punches to obtain Bilayer tablets.

We claim:
1. A controlled-release solid oral dosage form of Albendazole, comprising a gastroretentive release part and an enteric release part, wherein the gastroretentive release part comprises Albendazole, rate-controlling hydrophilic polymers, a gas-generating agent, superdisintegrants and at least one pharmaceutically acceptable excipient, and the enteric release part comprises Albendazole, a micro-environmental pH modifier, an enteric coating polymer, superdisintegrants and at least one pharmaceutically acceptable excipient.
2. The controlled-release solid oral dosage form of Albendazole as claimed in claim 1, wherein the rate-controlling hydrophillic polymers are selected from a group consisting of cellulose, cellulose derivatives including hydroxypropylmethylcellulose and hydroxyethylcellulose, cellulose esters, natural gums, polyvinylpyrrolidone, polyvinyl alcohol and polyethyleneoxide.
3. The controlled-release solid oral dosage form of Albendazole as claimed in claim 1, wherein the gas generating agent is selected from carbonates or bicarbonates.
4. The controlled-release solid oral dosage form of Albendazole as claimed in claim 3, wherein the gas generating agent is preferably selected from sodium carbonate, sodium bicarbonate, magnesium carbonate, calcium carbonate, aluminium carbonate or zinc carbonate.
5. The controlled-release solid oral dosage form of Albendazole as claimed in claim 1, wherein the microenvironmental pH modifier is selected from a group consisting of succinic acid, malic acid, fumaric acid, ascorbic acid, citric acid and tartaric acid.
6. The controlled-release solid oral dosage form of Albendazole as claimed in claim 1, wherein the enteric coating polymer is selected from a group consisting of acrylates, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, cellulose acetate trimellitate, polyvinyl acetate phthalate, hydroxypropyl

methylcellulose acetate succinate, carboxymethyl cellulose, alginic acid, alginate salts and shellac.
7. The controlled-release solid oral dosage form of Albendazole as claimed in claim 1, wherein the superdisintegrants are selected from a group consisting of crospovidone, croscarmellose sodium and sodium starch glycolate.
8. The controlled-release solid oral dosage form of Albendazole as claimed in claim 1, wherein the pharmaceutically acceptable excipient is selected from a group consisting of surfactant, solublizers, diluent, binder, filler, glidant, lubricant and buffer.
9. The controlled-release solid oral dosage form of Albendazole as claimed in claim 1, wherein the dosage form is selected from bilayer tablet, tablet in tablet, tablet in capsule, pellets in capsule or powders in capsule.