Process for making a lyophilized product for use in skeletal imaging

Claim 1

A process, for producing a dry-powder imaging composition, comprising the steps of: (a) preparing a solution which comprises a diphosphonate carrier, stannous reductant, and a stabilizer in water, wherein said diphosphonate is selected from the group consisting of compounds and mixtures of compounds having the formula ##STR4## wherein R 1 is hydrogen, alkyl containing from 1 to about 20 carbon atoms, amino alkyl, substituted amino alkyl, alkenyl containing from 2 to about 20 carbon atoms, aryl, phenylethenyl, benzyl, halogen, hydroxyl, amino, substituted amino --CH 2 COOH, --CH(COOH)CH 2 COOH, R 2 is hydrogen lower alkyl, amino, benzyl, halogen, hydroxyl, --CH 2 COOH, and the pharmaceutically-acceptable salts thereof, and said stabilizer is selected from the group consisting of ascorbic acid, erythorbic acid, substituted 5-deoxyascorbic acid, substituted 6-deoxyascorbic acid, pharmaceutically-acceptable salts and esters thereof, and compounds having the formula ##STR5## wherein X is CRR', O, NR', R' is hydrogen, or lower alkyl, Y is oxygen, sulfur, nitrogen, or CH 2 , R is hydrogen, lower alkyl, lower alkyl containing from 3 to 8 carbon atoms substituted with one or more hydroxy, halogen, amino or thiol groups, lower alkyl containing from 1 to 8 carbon atoms halogen-substituted on the first and/or second carbon atom, alkenyl containing from 2 to about 8 carbon atoms, nicotinic acid and nicotinamide complexes thereof; and pharmaceutically-acceptable salts, esters, and amides, and mixtures thereof; (b) adjusting said solution to a pH in the range from about 5.5 to about 6.5; and (c) lyophilizing said solution.