Drug – bio-affecting and body treating compositions – Designated organic nonactive ingredient containing other... – Carbohydrate or lignin – or derivative
Patent
1993-05-21
1996-02-20
Azouru, Carlos A.
Drug, bio-affecting and body treating compositions
Designated organic nonactive ingredient containing other...
Carbohydrate or lignin, or derivative
514944, 424426, 424428, 424430, 424434, 424435, 424436, 424437, 424445, A61K 4738
Patent
active
054929377
DESCRIPTION:
BRIEF SUMMARY
The present invention refers to a carrier composition which is liquid at or below room temperature and forms a high viscosity layer or gel at body temperature. The invention also refers to a pharmaceutical composition containing a pharmacologically active substance in combination with said carrier composition. Said compositions can be orally or locally administrated to the skin, the mucous membrane, the eye or a body cavity.
For local administration of a drug to different regions of the human body in order to obtain a local or systemic pharmacological effect the drug is normally combined with a semi-solid or liquid carrier to optimize drug uptake and administration. For many non-parental routes of administration there is often a need to prolong the duration of residence of the dosage form. This can be achieved by using a bioadhesive system, wherein the dosage form, by virtue of containing a bioadhesive polymer, adheres to the skin or the mucosa until the polymer dissolves or is replaced.
Polymers having bioadhesive properties are for instance water-soluble cellulose derivatives, such as sodium carboxymethyl cellulose, and polyacrylic acids, which are used in many pharmaceutical preparations to improve the contact between drug and body. If these polymers are administrated in liquid form they are, however, removed too fast. If a solid or viscous dosage form is used for local administration of drugs, there will on the other hand be limitations in the routes of administration and use in clinical practice.
Ophthalmic drugs delivered topically to the eye commonly have a low bioavailability. Rapid loss of the instilled drug via drainage through the drainage apparatus has a considerable influence. This loss leads to a short contact time between drug and cornea, making the drug less available for absorption into the eye. A well-known approach to improve the bioavailability of topically applied drugs is to prolong their corneal contact time. Improved uptake has been achieved by using vehicles containing viscosity-increasing polymers such as the cellulose derivatives, polyvinyl alcohol and polyvinylpyrrolidone. It is postulated that the increased viscosity results in reduced drainage of the instilled preparation, thereby increasing the bioavailability of the drug.
Thermogelling pharmaceutical preparations are described in for instance U.S. Pat. Nos. 4,478,822, 4,474,751, 4,474,752 and 4,474,753. Said patents refer to a drug delivery system which at room temperature has the properties of a liquid, but forms a semi-solid gel at human body temperatures. The compositions to be administered comprise 10 to 50% by weight of a polymer, which is a tetra-substituted derivative of certain diamines containing approximately 40 to 80% poly(oxyethylene) and approximately 20 to 60% poly(oxypropylene), as a drug delivery vehicle. In this system the gel transition temperature and/or the rigidity of the gel can be modified by adjustment of the pH.
Other systems are known in which the gelling is induced by an increase in the amount of electrolytes or a change in pH.
It has now surprisingly been found that certain water-soluble nonionic cellulose ethers in combination with a charged surfactant and optional additives in water have the property of being liquid at room temperature and forming a gel when warmed to body temperature. The process is reversible. These cellulose ethers also have been shown to have excellent bioadhesive properties. Such characteristics can be utilized for specialized drug delivery. The drug can be introduced on or into the body as a solution which will gel and adhere to body tissue just by means of the raise in temperature--no pH gradients or high electrolyte contents are required for the gelling.
The carrier composition of the invention is characterized in comprising a water-soluble, nonionic cellulose ether having a cloud point not higher than 40.degree. C., preferably not higher than 35.degree. C., a charged surfactant, and optional additives in water.
The carrier composition of the invention is also characteri
REFERENCES:
patent: 4042719 (1977-08-01), Zimmermann et al.
patent: 4474751 (1984-10-01), Haslam et al.
patent: 4474752 (1984-10-01), Haslam et al.
patent: 4474753 (1984-10-01), Haslam et al.
patent: 4478822 (1984-10-01), Haslam et al.
63-Pharmaceuticals, vol. 97, 1982, p. 413. Chem. Abstracts.
Bogentoft Conny
Carlsson Anders
Azouru Carlos A.
Pharmacia AB
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