Aqueous parenteral solutions of drugs which are insoluble or only sparingly soluble in water and/or which are unstable in water, combined with cyclodextrin selected from the group consisting of hydroxypropyl, hydroxyethyl, glucosyl, maltosyl and maltotriosyl derivatives of β- and γ-cyclodextrin, provide a means for alleviating problems associated with drug precipitation at the injection site and/or in the lungs or other organs following parenteral administration.

Pharmaceutical formulations for parenteral use

An effective amount of active/cyclodextrin complex, in the form of particles having particle sizes below about 12 microns, is incorporated into solid consumer product compositions. The complexes provide fast release of the active when they are wetted even when the amount of water available to effect release of the active is limited as in personal use compositions like drugs, foods, and cosmetics where active release is typically effected by body fluids. Preferred actives include perfumes, flavors, and pharmaceutical materials that are used by consumers.

Solid consumer product compositions containing small particle cyclodextrin complexes

The combination of a rapidly dissolving and supersaturating "spring" with a precipitation retarding "parachute" has often been pursued as an effective formulation strategy for amorphous solid dispersions (ASDs) to enhance the rate and extent of oral absorption. However, the interplay between these two rate processes in achieving and maintaining supersaturation remains inadequately understood, and the effect of rate of supersaturation buildup on the overall time evolution of supersaturation during the dissolution of amorphous solids has not been explored. The objective of this study is to investigate the effect of supersaturation generation rate on the resulting kinetic solubility profiles of amorphous pharmaceuticals and to delineate the evolution of supersaturation from a mechanistic viewpoint. Experimental concentration-time curves under varying rates of supersaturation generation and recrystallization for model drugs, indomethacin (IND), naproxen (NAP) and piroxicam (PIR), were generated from infusing dissolved drug (e.g., in ethanol) into the dissolution medium and compared with that predicted from a comprehensive mechanistic model based on the classical nucleation theory taking into account both the particle growth and ripening processes. In the absence of any dissolved polymer to inhibit drug precipitation, both our experimental and predicted results show that the maximum achievable supersaturation (i.e., kinetic solubility) of the amorphous solids increases, the time to reach maximum decreases, and the rate of concentration decline in the de-supersaturation phase increases, with increasing rate of supersaturation generation (i.e., dissolution rate). Our mechanistic model also predicts the existence of an optimal supersaturation rate which maximizes the area under the curve (AUC) of the kinetic solubility concentration-time profile, which agrees well with experimental data. In the presence of a dissolved polymer from ASD dissolution, these observed trends also hold true except the de-supersaturation phase is more extended due to the crystallization inhibition effect. Since the observed kinetic solubility of nonequilibrium amorphous solids depends on the rate of supersaturation generation, our results also highlight the underlying difficulty in determining a reproducible solubility advantage for amorphous solids.

Evolution of Supersaturation of Amorphous Pharmaceuticals: The Effect of Rate of Supersaturation Generation

Cyclodextrin complex is suspended in polyalkylene glycol carrier material that does not displace the included material. The preferred perfume/cyclodextrin complexes, either alone or admixed with solvent (e.g., water), are preferably suspended in the carrier and then incorporated into solid, dryer-activated, fabric treatment (conditioning) compositions, preferably containing fabric softeners, more preferably cationic and/or nonionic fabric softeners. The perfume complexes provide fabrics with perfume benefits when they are rewetted after drying. Volatile perfume materials, including those materials that are commonly associated with "freshness" can be applied to the fabrics in an effective way.

Non-destructive carriers for cyclodextrin complexes

The invention provides a method for the solubilization and/or stabilization of polypeptides, especially proteins, using a cyclodextrin selected from the group consisting of hydroxypropyl, hydroxyethyl, glucosyl, maltosyl and maltotriosyl derivatives of β- and γ-cyclodextrin. Solubilized and/or stabilized compositions comprising a polypeptide, especially a protein, and the selected cyclodextrin are also described.

Method and compositions for solubilization and stabilization of polypeptides, especially proteins

The invention relates to an inclusion complex of 1-(p-chloro-benzoyl)-5-methoxy-2-methyl-indol-3-yl-acetic acid (indomethacin) and cyclodextrin of a molar ratio of about 2:1 The inclusion complex can be prepared by reacting about 2 moles of alpha or beta cyclodextrin with about 1 mole of 1-(p-chloro-benzoyl)-5-methoxy-2-methyl-indol-3-yl-acetic acid under heating in the presence of an organic solvent which dissolves indomethacin and does not form a stable complex with cyclodextrin The new complex is at least as active antiinflammatory agent as indomethacin and at the same time shows substantially less ulcerative side-effect

Inclusion complex of cyclodextrin and indomethacin and a process for the preparation thereof, method of use and pharmaceutical composition

Antiallergic and particularly antiasthmatic compounds of the formula: ##STR1## of which 9-phenylhydrazono-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2-a)pyrimidine-3-carboxylic acid is an especially significant example.

Nitrogen bridgehead compounds having anti-allergic effect

Compounds of the formula ##STR1## or pharmaceutically acceptable acid-addition or quaternart ammonium salts thereof wherein R is hydroxy, carboxy, lower alkoxycarbonyl, benzyloxycarbonyl, phenoxycarbonyl, carbamoyl, N-loweralkyl-carbamoyl, N,N-dilower-alkyl-carbamoyl, carboazido, carbohydrazido or cyano; R 2 is C 1 to C 6 alkyl; R 3 is C 1 to C 6 alkyl or benzyl; and R 4 is a single electron pair, hydrogen or lower alkyl; and the dotted lines represent saturated or unsaturated bonds, are disclosed with analgesic properties.

Pyrido[1,2-A]pyrimidine derivatives and method of analgesic treatment

Compounds of the formula: ##STR1## or pharmaceutically acceptable salts thereof are disclosed wherein R is hydrogen or C 1 to C 6 alkyl; R 2 and R 3 are each hydrogen or together form a valency bond; R 6 is carboxy or C 1 to C 6 alkoxycarbonyl; R 7 and R 8 are each hydrogen or together form a valency bond; R 10 is carboxy or C 1 to C 6 alkoxycarbonyl and the dotted line represents two hydrogen atoms or a valency bond. The compounds are useful in the treatment of atherosclerosis.

Fused pyrimidine derivatives and compositions for treating atherosclerosis containing them

Compounds of the formula: ##STR1## or pharmaceutically acceptable acid addition or quaternary ammonium salts thereof wherein R 2 is C 1 to C 6 alkyl: R 3 is C 1 to C 6 alkyl; R 4 is a single electron pair, hydrogen or lower alkyl; and the dotted lines indicate saturated or unsaturated bonds, are disclosed with analgesic properties.

Virag Sandor

Papers

Inclusion complex of cyclodextrin and indomethacin and a process for the preparation thereof, method of use and pharmaceutical composition

Nitrogen bridgehead compounds having anti-allergic effect

Pyrido[1,2-A]pyrimidine derivatives and method of analgesic treatment

Fused pyrimidine derivatives and compositions for treating atherosclerosis containing them

Pyrido[1,2-a]pyrimidine derivatives