FORMULATION AND EVALUATION OF MUCOADHESIVE TABLETS OF CARVEDILOL USING NATURAL BINDERS

UNDER THE GUIDANCE OF,PRADIP DAS,M.PHARMASSISTANT PROFESSORPRESENTED BY,NAUSHEEN FATHIMA13DG1SO307TKR COLLEGE OF PHARMACY

1FORMULATION AND EVALUATION OF MUCOADHESIVE TABLETS OF CARVEDILOL USING NATURAL BINDERS

CONTENTS2INTRODUCTIONLITERATURE REVIEWAIM & OBJECTIVEPLAN OF WORKREQUIREMENTSDRUG & EXCIPENTS PROFILEPRE-FORMULATION STUDIESFORMULATION DEVELOPMENTEVALUATION TESTSCONCLUSIONREFERENCES

INTRODUCTION3Attachment of a synthetic or natural macromolecule to mucus or an epithelial surface- Mucoadhesion.For a material to be mucoadhesive, it must interact with mucus, which is a highly hydrated, viscous anionic hydrogel layer protecting the mucosa.The formation of non-covalent bonds such as hydrogen bonds and ionic interactions between the mucus gel layer and polymers provides a good mucoadhesion.

4Mucoadhesive polymers prolongs the residence time of dosage forms on the mucosa and hence the sustained drug release at a given target site can be achieved.

In biological systems, four types of mucodhesion could be distinguished as:Adhesion of a normal cell on another normal cell. Adhesion of a cell with a foreign substance.Adhesion of a normal cell to a pathological cell.Adhesion of an adhesive to a biological substance.

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5Mucoadhesive Drug Delivery System in Oral Cavity:Sublingual Delivery: Drugs are delivered through mucosal membrane lining the floor of mouth into systemic circulation.Buccal Delivery: Drugs are delivered through mucosal membrane into systemic circulation by placing drug in between cheeks and gums.Local Delivery: Drugs are delivered into the oral cavity.

Classification of Buccal Bioadhesive Dosage Forms: 1. Buccal Bioadhesive Tablets2. Buccal Bioadhesivc Semisolid Dosage Forms3. Buccal Bioadhesive Patches and Films4. Buccal Bioadhesive Powder Dosage Forms

LITERATURE REVIEW6Raviteja Achanta (2013) et al., formulated tablets of Thiocolchicoside which is muscle relaxant with anti-inflammatory and analgesic effects, using bioadhesive polymers like Carbopol 934p, HPMC K4M by direct compression method. In-vitro dissolution studies of the optimized formulation shows that the present drug release was 97.19% for 16 hrs.

Guda Aditya (2010) et al., formulated mucoadhesive buccal tablets of Lisinopril with a goal to increase the bioavailability, reduce dosing frequency and improve patient compliance. The tablets were prepared using Carbopol934p, Hydroxy Propyl Methyl Cellulose (HPMC), Hydroxy Ethyl Cellulose (HEC) as mucoadhesive polymers. Optimized formulation showed a drug release of 97.1% for 10 hrs and the formulation followed zero order kinetics.

7Charyulu Narayana R (2013) et al., prepared mucoadhesive matrix tablets of Acyclovir by direct compression using different types and levels of polymers like HPMC K15M, carbopol 934P, ethyl cellulose alone and in combinations. It was observed that combination of both the polymers in equal concentration exhibited the best release profile and able to sustain the drug release for 10 h.

Sellappan Velmurugan (2013) et al., formulated mucoadesive tablets of losartan potassium using polymers such as Carbopol 940P, Pectin, Sodium CMC, Sodium Alginate, HPMC K4M, HPMC K15M and HPMC K100M in alone and in combination as release retarding agent to prolong the drug release and to avoid first pass metabolism by direct compression method.

8Gururaj S.Kulkarni (2013) et al., prepared mucoadhesive buccal tablets of Terbutaline sulphate with natural polymer sodium alginate with one side absorption by backing layer with ethyl cellulose. It was found that mucoadhesive natural polymers exhibited better adhesiveness. The in vitro study of TS exhibited greater drug release profile with release of in the range of 79.25 to 99.85%.

Pramod Patil (2011) et al., prepared mucoadhesive tablets of Ofloxacin to prolong the gastric residence time after oral administration by wet granulation method. Different types of natural gums such as guar gum, locust bean gum and their combinations were used to formulate the mucoadhesive ofloxacin tablets. The optimized formulation showed drug release of 98.2% for 12hrs and the mucoadhesive strength was found to be good using a single compared to combinations.

AIM AND OBJECTIVE9Aim: To formulate and evaluate mucoadhesive tablets for antihypertensive drug Carvedilol using the natural binders chitosan and guar gum.Objective: Carvedilol is a nonselective beta blocker/alpha-1 blocker indicated in the treatment of mild to severe congestive heart failure and blood pressure. To conduct literature review of mucoadhesive drug delivery system.To select a suitable drug and excipients.To perform drug excipient compatibility studies as per ICH guidelines.To prepare and formulate by suitable methods.To evaluate in-vitro studies for the prepared mucoadhesive tablets.

PLAN OF WORK10Literature survey.Selection of materials used for development.Carrying out pharmaceutical development studies of carvedilol drug comprising of determination of API characteristics. Formulation of buccal tablets by using various concentrations.Evaluation of all physical parameters of prepared buccal tablets of Carvedilol.Evaluation of in-vitro drug release and optimization of best formulation.Results and discussion.

REQUIREMENTS11S.NoName of MaterialSource1CarvedilolMylan Laboratories2Carbopol-940PMerck Specialities Pvt Ltd3ChitosanSEZ Fine Chemicals4Guar gumSEZ Fine Chemicals5Cross Carmellose SodiumSD Fine Chem Ltd6LactoseDSE Pharma7Magnesium StearateFerro Corpotation8TalcLuzenac Pharma

LIST OF CHEMICALS

LIST OF INSTRUMENTS12S.NoInstrumentsManufacturer1Electronic weighing balanceDenver instrument2Melting point apparatusSETCO Ltd, Banglore3UV-Visible SpectrophotometerShimadzu, Japan4FTIR SpectrophotometerShimadzu, Japan5Tablet Punching MachineCADMACH, Mumbai6Friabilator USP EF-2Electrolab, Mumbai7Monsanto Hardness TesterKetan Engineering Ltd, Mumbai8Dissolution Test ApparatusElectrolab, Mumbai9Digital pH meterMitutoyo, Japan10Stability ChamberLab Control Equipment Co. Mumbai

DRUG PROFILE13CARVEDILOLCategory: Antihypertensive, Vasodilator Agents, Adrenergic alpha-1 Receptor Antagonist, Adrenergic beta-AntagonistIUPAC Name:()-[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl] [2-(2-methoxyphenoxy) ethyl] amineMolecular Formula: C24H26N2O4Molecular Mass: 406.474g/molStructure:Properties:Melting Point: 114.5CHalf-life: 6 hrs.Bioavailability: 25-35%

14Solubility: Soluble: Ethanol , methanol , phosphate buffer.Partially: Water, chloroform, methylene chlorideInsoluble: Isopropanol

Mechanism of action: Carvedilol's beta-adrenergic receptor blocking ability decreases the heart rate, myocardial contractility, and myocardial oxygen demand. Carvedilol and its metabolites also prevent OH- radical-induced decrease in sarcoplasmic reticulum Ca2+-ATPase.

Metabolism: Carvedilol is metabolized primarily by aromatic ring oxidation and glucuronidation.

15Absorption: Carvedilol is rapidly and extensively absorbed following oral administration, with an absolute bioavailability of approximately 25% to 35% due to a significant degree of first-pass metabolism.

Route of Elimination: Less than 2% of the dose is excreted unchanged in the urine. The metabolites of Carvedilol are excreted primarily via the bile into the feces.

Contraindications: Asthma, cardiogenic shock, hepatic dysfunction, hypersensitivity.

Side Effects: Dizziness, fatigue, hypotension, diarrhea, bradycardia, weight gain.

EXCIPIENT PROFILE16GUAR GUM

Synonym: Jaguar gum, galactosolCategory: Binder, disintegrant, viscosity increasing agent.Molecular Formula: (C6H12O6)nMolecular Weight: 25,000 DaltonsMelting Point: 90CDescription: nearly odorless, white to yellowish-white powder with a bland taste.Solubility: insoluble in organic solvents. In cold or hot water, guar gum disperses and swells almost immediately to form a highly viscous, thixotropic sol.

17CHITOSAN

Synonyms:Chitosani hydrochloridum; deacetylated chitin; deacetylchitin.Category: Coating agent, mucoadhesive tablet binder, viscosity increasing agent.Molecular Formula: (C8H13NO5)nMolecular Weight: 1526.45g/molDescription: Chitosan occurs as odorless, white or creamy-white powder or flakes. Particle size distribution: