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Friday, May 15, 2009

BUCCAL BIOADHESIVE DRUG DELIVERY SYSTEMS

BUCCAL BIOADHESIVE DRUG DELIVERY SYSTEMS

K. R. Resmi MolHH,
Teena K Thomas,
Vimal Mathew

National College of Pharmacy, Manassery, Calicut


 

INTRODUCTION


 

    Over the decade, controlled drug delivery and site-site-specific drug delivery have made rapid advances. Bioadhesive systems now play a major role in this field, due to their interesting potentialities. Besides acting as platforms for sustained release dosage forms, bioadhesive polymers can themselves exert some control over the rate and amount of drug release, and thus contribute to the therapeutic efficacy of bioadhesive drug delivery system2.


 

    Bioadhesion and bioadhesives are classified in to three type based on phenomenological observation.


 

Type-I     It is characterized by adhesion occurring between biological objects
    without involvement of artifical materials1.

Type-II     It refers to adhesion of biological materials to artificial substrates.
    Ex. Cell adhesion onto culture dishes1.

Type-III    It refers to adhesion of artificial substrates to biological substrates.
    Ex. Adhesion of polymers to skin or other soft tissues1.


 

    Bioadhesive polymers are polymers that will attach to relate tissues or the surface coating of the tissues. In case of polymer attached to the mucin layer of mucosal tissue, the term "mucoashesive" is employed. The idea of mucoadhesive came in to existence from the need to localize drug at a certain site in the body. Often, the extent of drug absorption is limited by the residence time of the drug at the absorption site. In oral drug delivery, the drug absorption is limited by the gastrointestinal transit time of the dosage form. Since many drugs are absorbed only from the upper small intestine, localizing oral drug delivery systems in the stomach or duodenum, would significantly improve the extent of drug absorption. Mucoadhesion phenomenon satisfied the following features of controlled release systems.


 


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    FACTORS AFFECTING BIOADHESION


     


     

        There is an optimum concentration of polymer corresponding to the best bioadhesion. In highly concentrated system, the adhesive strength drops significantly.


     


     


     


     


     

        pH was found to have a significant effect of mucoadhesion are observed in studies of polyacrylic polymer cross linked with COOH group. pH influences the charge on the surface of both mucus and the polymers. Mucus will have a different chart density depending on pH because of differences in dissociation of functional groups on the carbohydrate moity and amino acids of polypeptide backbone.


     

        Polycarbophil show the maximum adhesive strength at pH 3, the adhesive strength decreases gradually as the pH increases upto 5 polycarbophil does not show any mucoadhesive property above pH 5. This study, the first systematic investigation of the mechanism of mucoadhesion, clearly shows that the protonated carboxyl group rather than ionised carboxyl group react with mucin molecules presumably by numerous simultaneous hydrogen bond.


     


     

        The polymer molecule must have an adequate length.


     

        The optimum molecular weight for the maximum bioadhesion depend on the type of polymers. The bioadhesive forces increases with the molecular weight of bioadhesive polymer.


     


     

        It is important for interpenetration and enlargement. As water soluble polymers become cross linked, the mobility of the individual polymer chain decreases. As the cross linking density increases, the effective length of chain which can penetrate into the mucus layer decreases even further and mucoadhesive strength is reduced1.


     

    BUCCAL BIOADHESIVE DRUG DOSAGE FORM


     

        Buccal bioadhesive dosage forms are specialised dosage form which adhere to buccal mucosa for specific period of time and deliver the drug therein for local or systemic effect.


     

        Because of the presence of smooth relative immobile surface of placement of bioadhesive dosage form, the buccal region appears to more suitable for controlled delivery of the therapeutic age using a bioadhesive system.


     

        There is a limit to the size of the bioadhesive dosage form. Only a limited amount of drug can be used in this system. In general any drug with a daily requirement of 25mg or less is suitable for buccal delivery14.


     

    ADVANTAGES OF BUCCOBIADHESIVE DRUG DELIVERY SYSTEMS


     


 

DISADVANTAGES OF BUCCOBIOADLIESIVE DRUG DELIVERY SYSTEM


 

The disadvantages of buccal bioadhesive drug delivery systems are as follows:


 


 

LIMITATIONS OF BUCCOBIOADHESIVE DRUG DELIVERY SYSTEM:


 

The drug administration via buccal route has certain limitations,


 

BASIC COMPONENTS OF BUCCAL BIOADHESIVE DRUG DELIVERY SYSTEM


 

The basic components of buccal bioadhesive drug delivery system are


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    1. DRUG SUBSTANCE


     

        Before formulating buccoadhcsivc drug delivery systems, one has to decide whether the intended, action is for rapid release/prolonged release and for local/systemic effect. The selection of suitable drug for the design of buccoadhesive drug delivery systems should be based on pharmacokinetic properties. The drug should have following characteristics12:


     

    The drugs having biological half-life between 2-8 hours are good candidates     for controlled drug delivery.

    Through oral route drug may exhibit first pass effect or presystemic drug     elimination.


 


 


 


 


 

2. BIOADHESIVE POLYMERS


 

The first step in the development of buccoadhesive dosage forms is the selection and characterization of appropriate bioadhesive polymers in the formulation." Bioadhesive polymers play a major role in buccoadhesive drug delivery systems of drugs. Polymers arc also used in matrixdevices in which the drug is embedded in the polymer matrix, which controls the duration of release of drugs.11 Bioadhesive polymers arc by for the most diverse class and they have considerable benefits upon patient health care and treatment.13 The drug is released into the mucous membrane by means of rale controlling layer or core layer. Bioadhesive polymers which adheres to the mucin/ epithelial surface are effective and lead to significant improvement in the oral drug delivery.1


 


 

    An ideal polymer for buccoadhesive drug delivery systems should have following Characteristics.12


 


 

Criteria followed in polymer selection


 


 

BUCCAL BIOADHESIVE TABLETS


 

    Buccal bioadhesive tablets are dry dosage forms, that are to be moistened prior to placing in contact with buccal mucosa. Double and multilayered tablets are already formulated using bioadhesive polymers and excipients. The two buccal bioadhesive tablets Commercially available buccoadhesive tablets in UK are "Bucastem" (Nitroglycerine) and " Suscard buccaP'(Prochloroperazine).

Examples:     Nitroglycerin bioadhesive tablets for the treatment of anginapectories.1


 

    Sumatriptan succenate buccal adhesive tablet which is effective in the acute treatment of mygrain and cluster headache.13


 

    Verapamin buccal tablet with compressed verapamin (15ml) mucoadhesive polymer like sodium alginate and HPC - EXF with standard tablet excepitints.


 

BUCCAL BIOADHESIVE PATCHES AND FILMS


 

Buccal bioadhcsivc patches consists of two ply laminates or multilayercd thin film round or oval as consisting of basically of bioadhesivc polymeric layer and impermeable backing layer to provide unidirectional flow of drug across buccal mucosa. Buccal bioadhcsivc films arc formulated by incorporating the drug in alcohol solution of bioadhesive polymer.

Example: Isosorbid dinitrate in the form of unidirectional errodible buccal film are developed and characterised for improving bioavailability.


 

Buccal film of salbutamol sulphate and terbutalin sulphate for the treatment of asthma.


 

Buccoadhesive film of clindamycin used for pyorrhoea treatment.


 

BUCCAL BIOADHESIVC SEMISOLID DOSAGE FORMS


 

Buccal bioadhesive semisolid dosage forms consists of
finally powdered natural or synthetic polymer dispersed in a polyethylene or in aqueous solution, Example: Arabase.16


 

BUCCAL BIOADHESIVE POWDER DOSAGE FORMS


 

    Buccal bioadhesive powder dosage forms are a mixture of bioadhesivc polymers and the drug and are sprayed onto the buccal mucosa


 


 

The figure shows the reduction in diastolic B.P after the administration of buccal tablet and buccal film of Nefedipine.1


 

DEVELOPMENT & IN VlTRO EVALUATION TASTE MASKED BUCCAL DOSAGE FORM OF AN ANTIMIGRAINE AGENT


 

Introduction


 

Taste masked buccal dosage form of Sumatriptan_Succinate (SS) was prepared by wet granulation method. Initially placebo buccal tablets were prepared by using combination of various bioadhesive polymers and normal tablet excipients & optimized on the basis of bioadhesive strength. Various taste masking trials were carried out and finally taste masking was done by complexation with ion - exchange resin. Drug - resin complex was then loaded in the optimized formulations. The final formulation was optimized on the basis of pharmacopoeial tablet tests, bioadhesive strength & in-vitro release studies.


 

    SS is a serotonin {5 HT,) receptor agonist, which is effective in the acute treatment of migraine & cluster headache Following oral administration, SS is rapidly but incompletely absorbed & undergoes extensive hepatic first pass metabolism, resulting in low absolute bioavailability of 14%. Peak plasma concentration occurs within 2 hours. It also has a short elimination half life of about 2 hours . The taste of the drug is also very bitter & it is thus needed to mask the taste of the drug. All these parameters clear!, warrant the development of a dosage form with improve bioavailability, better patient compliance & hence improve: efficacy. Therefore, the aim of the present study was to first mask the taste of the drug and then develop its buccal dosage form. 13


 

Experimental


 


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    Results and Discussion


     

        The present study was an attempt to develop a buccal delivery system for the systemic delivery of SS through the buccal cavity. Since SS is a very bitter drug and has to be absorbed and permeated through the buccal cavity from the delivery system, it was necessary to first mask the taste of the drug & then formulate it as buccoadhesive tablets. The combination of HPMC K4M/Cekoi 300/CP 974/MaHodextrin showed good bioadhesive strength in placebo tablets. During complex formation, highest degree of complexation" at pH 6.0 (99.25% of the drug was complexed with in the resin). Drug loading into the placebo tablets significant decrease their bioadhesive strength & work of adhesion. Optimized tablets gave maximum in-vitro release of 92.98% in IPB pH 6.6 & 95.70% in 0 IN HCI over a 6h period.


     

    Conclusion


     

        The taste masked buccal dosage form of SS was successfully developed. In-vitro studies showed that the formulation has good potential in the treatment of migraine & cluster headache. Permeation studies & In-vivo studies are being carried out to prove its clinical usefulness & patient compliance.


     

    CONCLUSION


     


     

        The buccal mucosa offers several advantages over controlled drug delivery for extended periods of time. The mucosa is well supplied with both vascular and lymphatic drainage and first-pass metabolism in the liver and pre-systemic elimination in the gastrointestinal tract are avoided. The area is well suited for a retentive device and appears to be acceptable to the patient. With the right dosage form design and formulation, the permeability and the local environment of the mucosa can be controlled and manipulated in order to accommodate drug permeation. Buccal drug delivery is a promising area for continued research with the aim of systemic delivery of orally inefficient drugs as well as a feasible and attractive alternative for non-invasive delivery of potent peptide and protein drug molecules. However, the need for safe and effective buccal permeation absorption enhancers is a crucial component for a prospective future in the area of buccal drug delivery.


     


     

    REFERENCE


     


     


     


     


     

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