United States Patent:  5,989,535

Assignee:  Soma Technologies (Morganville, NJ)

Filed:  August 15, 1997

Bioadhesive/mucoadhesive composition in a suspension or emulsion form that delivers drugs to the target tissue in a sustained manner is formulated. A composition, method of manufacture and its application in treatment of mammalian tissue are disclosed. The composition includes a bioadhesive/mucoadhesive polymer in an emulsion or suspension form along with a treating agent. The treating agent could be as simple as water as in the case of mucoadhesive moisturizing agent. The bioadhesive/mucoadhesive polymer is a water dispersible high molecular weight crosslinked polyacrylic acid copolymer with free carboxylic acid groups further crosslinked with a combination mono, di and polyvalent metal ions, cationic polymers and surfactants. Type of metal ion and their concentration can be adjusted to get the desired bio/mucoadhesive properties along with several physical properties that are important to the formulation of dosage forms. The viscosity of the formulation can be reduced substantially by crosslinking with metal ions or by incorporating anions or cations in 0.01 to 5% to get low viscosity product with higher polymer concentration, which is important in several dosage forms. The concentration of the polymer ranges from 0.05 to 20.0 percent depending on the crosslinking and the viscosity of the product.

BRIEF DESCRIPTION OF THE INVENTION

This invention describes bio/mucoadhesive compositions that contain crosslinked carboxy-functional polymer which is water--swellable and water soluble that can be made water insoluble by one or more of the following chemical or physical interactions:

a) chemical interaction with mono, di or poly valent cations to reduce the solubility

b) chemical interaction with a combination of mono, di and polyvalent ions to reduce solubility

c) Physical interaction between mono, di and trivalent anions to reduce solubility

d) Chemical interaction with amino functional organic compounds to reduce solubility

d) physical and chemical interaction between two different polymer strands to produce large insoluble molecule

e) Utilize combinations of all of the above.

The finely divided crosslinked carboxy-functional copolymer is dispersed in a hydrophobic medium to get a pourable consistency which is then added to an aqueous solution containing the said ingredients that modify the properties of the major polymer to get an oil in water emulsion, latex or suspension. Traditionally, these type of polymers are very difficult to distribute in hydrophilic medium in large quantity due to the high viscosity of the dispersions. Viscosity is the limiting factor in incorporation of hydrophilic polymers in hydrophilic medium. Concentration of the polymer will dictate the outcome of sustained release or bioadhesion to the target site. In majority of the cases it is impossible to disperse even two percent polymer in aqueous systems without any lump formations. High-energy input is required in this type of system to incorporate even small amount of polymers. This invention overcomes problems associated in incorporation of large amount of polymer in the hydrophilic systems even to the extent of 10 to 20 percent with substantial reduction in the viscosity of the final product so that the resulting formulation has usable range of viscosity for therapeutic use. The final products prepared from this invention have better consumer acceptance due to the superior physical characteristics compared to the marketed products. These types of compositions can be used to administer drugs systemically or locally in sustained or immediate release dosage forms. Compositions of the invention can be formulated as liquids, creams, gels, suspensions, emulsions, soft gelatin capsules, hard gelatin capsules and hard-boiled candy with center fills.

Claim 1 of 18 Claims

1. Sustained release treatment compositions useful for application to biological surfaces comprising skin and mucous membranes of various organs and tissues, said composition containing medicament, water-soluble, and water-swellable polymners, said polymers containing at least 25% by weight of carboxylic acid groups crosslinked with a crosslinking agent selected from the group consisting of polyalkenyl polyether or divinyl benzene, said polymer being present in amounts of 0.05-20 weight percent and being further physically or chemically interacted with a single or a combination of mono, di and polyvalent metallic cations or anions to obtain cross-linked co-polymers of high molecular weight with reduced viscosity and solubility but with enhanced bioadhesive properties, said composition further being comprised of hydrophilic or hydrophobic carrier or a mixture of the same.

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