CRYSTALLIZATION METHOD AND BIOAVAILABILITY
Preparation and in vitro and in vivo characterization of novel forms of active pharmaceutical ingredients, suitable for pharmaceutical compositions in drug delivery systems for humans.
1 . A composition comprising at least one API and at least one coformer.
2 . The composition of claim 1 , wherein at least one of the at least one coformer is a molecular complex coformer and, wherein the API and the molecular complex coformer form a molecular complex.
3 . The composition of claim 2 , wherein the molecular complex consists of zoledronic acid, DL-lysine and water.
4 . A pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable excipient that is not a coformer.
5 . The pharmaceutical composition of claim 4 , wherein the coformer increases the oral bioavailability of the API.
6 . A unit dose of the pharmaceutical composition of claim 4 .
7 . The unit dose of claim 6 , wherein the unit dose is an oral dosage form.
8 . The unit dose of claim 7 , wherein the oral dosage form is a tablet or capsule.
9 . The unit dose of claim 8 , wherein the tablet or capsule is enteric coated.
10 . The unit dose of claim 7 , wherein the unit dose is no more than 2.5 mg/kg (mg zoledronic acid/kg patient), and wherein the unit dose is at least equivalent in efficacy to a 4 mg unit dose of the marketed form ZOMETA (or its equivalent) administered intravenously.
11 . A pharmaceutical enteric coated oral dosage form comprising:
a. a zoledronic acid molecular complex, and
b. a pharmaceutical acceptable excipient,
where said the pharmaceutical enteric coated oral dosage form is suitable for oral administration and has an improved safety profile over the corresponding oral dosage form without an enteric coating.
12 . The enteric coated oral dosage form of claim 11 , wherein the pharmaceutical enteric coated oral dosage form comprises an amino acid selected from glycine or lysine.
13 . The enteric coated oral dosage form of claim 11 , wherein the zoledronic acid molecular complex is a sodium salt of zoledronic acid.
14 . The enteric coated oral dosage form of claim 13 , wherein the sodium salt of zoledronic acid is disodium zoledronate.
15 . The enteric coated oral dosage form of claim 13 , wherein the sodium salt of zoledronic acid is disodium zoledronate tetrahydrate.
16 . The pharmaceutical enteric coated oral dosage form of claim 12 , wherein the pharmaceutical oral dosage form is a tablet comprising:
a. a core comprising the zoledronic acid molecular complex and the amino acid;
b. a first coating comprising a pharmaceutically acceptable polymer; and
c. a second coating, wherein the second coating is an enteric coating.