ENHANCE BIOAVABILITY OF ALBENDAZOLE DRUG BY MESOPOROUS MATERIAL

Paras Bodana 1 , Girver Kelkar 1 , Shelendra Kumar Manglavat 1 , Arun Kumar Gupta 1 and S. C. Chaturvedi 2 . 1. School of Pharmacy (RKDF IPS), Dr. A.P.J. Abdul Kalam University Indore Bypass Road, Arandia Village, Post Jhalaria, Indore, Madhya Pradesh 452016. 2. Shri Aurbindo Institute of Pharmacy, Indore. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History

Mesoporous silica nanoparticles (MSN) have gained attention for potential as controlled release systems and vechicles for the delivery of chemotherapeutics due to high surface areas, large cavity volumes and ability to be fictionalized with biomolecules for the targeting of specific tissue by using Mesoporous material with Albendazole drug enhance Bioavability. Various Mesoporous silica structure incorporation of heteroatoms such as Cu, Zn, Al and Fe etc. into Mesoporous silica framework has been investigated .Mesoporous materials are used because of their ability of their desirable characteristics such as high surface area, large pore volume, and tunable Mesoporous channels with well defined pore size distribution, controllable wall composition as well as modification surface properties. According to the nomenclature by International Union of pure and applied chemistry (IUPAC). Albendazole is an antihelmintic drug whose solubility is low by Using Mesoporous material than Bioavability of Albendazole are Enhanced.

…………………………………………………………………………………………………….... Introduction:-
In present Scenario with advancement in control drug delivery sytem.Multiple drugs are present in market 40 % are poorly water soluble whose bioavaibility is low. (Davis me et.al) Oral dosage forms, especially tablets are one of the most convenient formulation forms, as well in fabrication and administration. The production costs are very low compared to other dosage forms. Tablets have lots of advantages such as ease of transportation,easier delivery espically in elderly patients with low vision, patient compliance and accurate dosing (Sayari A et.al).
The tablet formulation of lot of potential hydrophobic and lipophilic drug molecules can be very problematic due to their poor pharmacokinetics/ADME parameters. These include a low solubility in the stability range of temperature and or a dissolution rate of the drug in the intestinal lumen, low permeation properties through the gastrointestinal (GI) wall and rapid intestinal wall metabolism or high hepatic first pass effect. The oral bioavailability of these molecules can be very low because the rate of absorption of the drug is restricted by the poor dissolution through out the GI tract (M. Hartmann et.al Mobile corporation first introduced mobile crystalline material (MCM)-41,a large body of research has been devoted to developing novel mesoporous silica materials with controlled pore size and uniform pore structure (Hoffmana A et.al).
Recently, mesoporous silica nanoparticles (MSN) have gained attention for potential as controlled release systems and vechicles for the delivery of chemotherapeutics due to high surface areas ,large cavity volumes and ability to be fuctionalized with biomolecules for the targeting of specific tissue. Various Mesoporous silica structure incorporation of heteroatom's such as Cu, Zn, Al and Fe etc. into Mesoporous silica framework has been investigated . (Breck, D.W et.al). In recent years, Mesoporous materials, which have unique pore size, higher surface area and pore volume, have been used widely employed as carriers for drug delivery (Breck, D.W et.al).
Up to 40 % of new chemical entities (NCEs) discovered by 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. Low drug solubility often manifacts itself in a host of In vivo consequences, including decreased bioavailability ,increase chance of food effect more frequent incomplete release from the dosage form and higher interpatient variability (Alothman, Z.A et.al).
Poorly soluble compounds also present many in vitro formulation obstracles ,such as severely limited choices of delivery technologies and increasingly complex dissolution testing with limted or poor correlation to the in vivo absorption. Ordered Mesoporous silica material have recently attracted much attention because of their emerging application in drug delivery, Since their first appearance in materials science in the 1990s these inorganic carriers have been successfully used in area such as catalysis, purification and adsorption (Davis, M.E et.al).
Meso, the Greek prefix, meaning-in between, has been adopted by IUPAC to define porous materials with pore sizes between 2.0 and 50.0 nm. Mesoporous are present in aerogels and pillared layered clays which show disordered pore systems with broad pore size distribution. A constant demand has been developed for larger pores with well defined 2520 pore structure. The design and synthesis of organic, inorganic, and polymeric materials with controlled pore structure are important academic and industrial research projects, Many potential application require specific pore size, so that the control of pore dimensions to within a portion of an angstrom can be dividing line between success and failure. Zeolites and zeolite -like molecular sieves (zeotype) often fulfill the requirements of ideal porous materials such as narrow pore size distribution and a readily tunable pore size in a wide range (Alothman, Z.A et.al).
These new silicate materials possess extremely high surface areas and narrow pore size distribution .Rather than an individual molecular directing agent participating in the ordering of the reagents forming the porous materials, assembles of molecules, dictated by solution energetic, are responsible for the formation of these pore systems. This supramolecular directing concepts has led to a family of materials whose structure, composition, and pore size can be tailored during sysnthesis by variation of reactant stoichiometry, the nature of the surfactant molecules, the auxiliary chemicals, the reaction condition, or by the post-synthesis functionalization techniques. Recently, Mesoporous materials are used because of their ability of their desirable characteristics such as high surface area, large pore volume, and tunable Mesoporous channels with well defined pore size distribution, controllable wall composition as well as modification surface properties. According to the nomenclature by International Union of pure and applied chemistry (IUPAC) porous material defined in 3 category. Due to the distinct Mesoporous structure, mesoporous materials have demonstrated their unique advantage . ( In 1949 and 1954 Breck and coworker were able to synthesize a number of new zeolites (types A,X and Y) which were produced in large scale to be used for the separation and purification of small molecule.The success synthesizing crystalline aluminiumsilicates in particular the emergence of the new family of alumino -phosphate and silico aluminophosphates ( Dias, F et.al).

BCS classification (Biopharmaceutical):-
BCS is a direction for owing the intestinal drug absorption provided by USFDA.

Class I:-
Highly permeable and highly soluble drugs well absorbed and their absorption rate is greater than excretion. For those class I compounds formulated as immediate release products, dissolution rate generally exceeds gastric emptying. Therefore, nearly 100% absorption can be expressed if at least 85% of a product dissolves within 30 min of in vitro dissolution testing across a range at pH values eg. Metoprolol, Propranolol, verapamil, paracetamol, choloraquine etc.
Class II:-Highly permeable and low soluble, limited bioavailability due to their salvation rate in vitro drug dissolution is then a rate limiting step for absorption except at a very high dose number. e.g Naproxen, Carbamezepine, phenytoin, Nifedipine.
Class III:-Low permeable and high soluble,limited absorption by permeation rate but the drug is solvated fast .these drug exhibit a high variation in the rate and extent of drug absorption.Absoption is permeability-rate limited but dissolution will most likely occur very rapidly. e.g Cimetidine, Ranitidine, Atenolol, Acyclovir, Captopril, Metformin, Albendazole.
Class IV:-Low permeable and low soluble,those having poor bioavailability,usually not absorbed by the GI mucosa.These compounds are not only difficult to dissolve but once dissolved, often limited permeability across the GI mucosa.These drug tend to be very difficult to formulate and can exhibit very large inter subject and intra subject variability.  Table: Relationship between Angle of Repose (0) and flow properties. A funnel was filled to the brim and the test sample was allowed to flow smoothly through the orifice under gravity. From the cone formed on a graph sheet was taken to measure the area of pile, thereby evaluating the flowability of the granules. Height of the pile was kept constant to 2cm measured.
Bulk Density:-Bulk density is defined as the mass of a powder divided by the bulk volume. The bulk density of a powder depends primarily on particle size distribution, particle shape, and the tendency of the particles to adhere to one another. The bulk density of a powder depends on particle packing and changes as the powder consolidates. A consolidated powder is likely to have a greater arch strength then a less consolidated one and may therefore be more resistant to powder flow. The ease with which a powder consolidates can be used as an indirect method of quantifying powder flow. Method:-Both loose bulk density (LBD) and tapped bulk density (TBD) were determined by tap density tester. A quantity of accurately weighed powder from each formula, previously shaken to break any agglomerates formed was introduced into a measuring cylinder. After the initial volume was observed, the cylinder was allowed to fall under its own weight onto a hard surface from the height of 2.5 cm at 2 seconds interval. The taping was continued until no further change in volume was noted. LBD and TBD were calculated using following formula

LBD = (M) / (VO)
Where M is the weight of powder and VO is the volume after tapping.

TBD = (M) / (V f )
Where M is the weight of powder and V f is the final volume without tapping.

UV Spectrophotometric Analysis Of Drug Sample:
100 mg of albendazole was taken in a 100 ml volumetric flask and volume was made upto the mark with methanol hydrochloric acid to produce a stock solution of 1000 µg/ml. From this solution, solution of 100µg/ml was prepared and sample was scanned between 200-400 nm on a double beam UV/Vis spectrophotometer.

Ft-ir spectroscopy of albendazole drug sample:-
The flourier transform infrared (FT-IR) spectroscopy of the albendazole drug sample was performed using KBr pellets and the spectrum so obtained. IR spectrum of any compound gives information about the group present in particular compound. IR transmission spectra were obtained using infrared spectrophotometer. An infrared spectrum of drug was taken using KBr pellets. Small quantity of drug was used for IR analysis. The pellets were placed in holder and an infrared spectrum was taken. The scanning range was 400-4000 cm− 1; various peaks in infrared spectrum were interpreted for presence of different group in the structure of drug (Albendazole).      Dissolution Profile:-Amount of drug are taken in a 0.1N HCL in 1000ml Basket and dissolution carried out at different interval of time.

Result and Discussion:-
Albendazole is one of the most effect API for management of an then disease in pediatric and geriatric patient but it was strumming with poor aqueous solubility profile which enhances the change of its tissue accumulation as well as life threating process. Out of the various solubility enhance alternate to counter act with percent solubility problem of APIs. Consideration the Above mention fact various batch with various concentration magnesium aluminum silicate as Mesoporous formulation prepared and evaluated out of the F8 was form to be most competition one.
Since it effective overcome the solubility problem and further facilitate the bioavailability of API in the dissolution media.
The detailed result and dissolution of F8 formulation were as follows.
The tablets were found to be welled shape with while to off white appearance process a smooth surface texture. The diameter and thikness found to be 4.30mm with the help of screw gauge and it was compatible with prescribed parameter in Monograph. The hardness and weight variation test of tablet were performed with Pfizer the result ar4.4kg/cm 2 .The hardness was found to be 4.4 ± kg/cm 2 which already indicate its compatibility nature to that of required sustained release.
The friability was performed with the help of Roche friability0.58The result clearly indicate that initial batches failure but in case of F8 batch when we take combination of magnesium aluminum silicate and PVP in large amount it provide good result.  Finally e perform the dissolution with the help of diisolution apparatus successive 3set of batch were evaluated by using .1N HCL PH 2-3 as a dissolution media which was suppose to mimic the stomach concentration and appearance was kept at themostate at 370 c ± 10C at regular the sample were with drug and analytically media it aliquates with the help of U.V Spectroscopy meter. Finally a drug release pattern was obtain between percent drug Finally on the basis optimization evaluated it can be consider as that mesoporous formulation is a better alteration for solubility enhance of Albendazole and can be employed effective Mesoporous material always remain a preferable choice for academic and industrial researcher for solubility as well as bioavailability enhancement of API in present thesis through they are successfully is achieve in a desired solubility profile but there is al lot to do regarding its solubility concert and its dosage form design in various formulation prospect. In the context to the above mention various form urgent need of its clinical evaluation which may possible to perform in near future.

Summary and Conclusion:-
The objective of the present research is Formulation and characterization of tablet "Albendazole". The sample of Albendazole procured for "Syncom pharmaceutical limited pithampur Indore" and was characterized by Melting point, IR analysis and UV analysis.
The results were similar to the one reported in the official compendia, hence the procured drug samples were considered as pure and used for further studies. In drug discovery, about 40% of new drug candidates display low solubility in water, which leads to poor bioavailability, and lack of dose proportionality. Therefore, producing suitable formulations is very important to improve the solubility and bioavailability of such drugs. One of the most popular and commercially viable formulation approaches for solving these problems is solubility. Albendazole tablet has proved batter action in compare to sustain release dose. In this study that mainly focus on the preparation and characterization of a Albendazole formulation in a systemic way, especially with respect to dosage form development and preparation techniques. In this present study, selection of each ingredient for Albendazole formulation based on following parameters; Sustain release Pre-formulation studies were performed to identify the desirable tablet region where it dissolve and to determine the dissolution factors Solubility study of drug, Drug-Excipient compatibility studies, Flow property of powder, Loss of drying, Bulk density, Melting point, Tapped density, Angle of repose, carr's Index, Haussener's ratio of powder.
Post-formulation studies were performed to find out Bulk density, Tapped density, Angle of repose, carr's Index, Haussener's ratio of granules. Formulation studies were performed Dissolution of tablet, Drug content, UV analysis, disintegration of tablet, Hardness of tablet, Friability, Weight variation of tablet.
Albendazole is one of the most effect API for management of an then disease in pediatric and Geriatric patient but it was strumming with poor aqueous solubility profile which enhance the change of its tissue accumulation as well as life treating process.
Out of the various solubility enhance alternate to counter act with percent solubility problem of APIs. Consideration the Above mention fact various batch with various concentration magnesium aluminum silicate as Mesoporous formulation prepared and Evaluated out of the F8 was form to be most competition one.Since it effective overcome