Taste Making Formulation Comprising The Drug In A Dissolution-Retarded Form And/Or Cyclodextrin In A Dissolution-Enhanced Form
Improved taste masking of pharmaceutical compositions of unpleasant-tasting drugs and cyclodextrin is achieved by forming a mixture of drug and cyclodextrin wherein the drug's dissolution rate has been retarded, or the the cyclodextrin's dissolution rate has been enhanced, or by both.
1 . A pharmaceutical composition comprising a physical mixture of
(a) an unpleasant-tasting drug in solid form; and
(b) a cyclodextrin in solid form;
wherein said drug is in a dissolution-retarded form.
2 . A pharmaceutical composition comprising a physical mixture of
(a) an unpleasant-tasting drug in solid form; and
(b) a cyclodextrin in solid form;
wherein said cyclodextrin is in a dissolution-enhanced form.
3 . A pharmaceutical composition comprising a physical mixture of
(a) an unpleasant-tasting drug in solid form; and
(b) a cyclodextrin in solid form;
wherein said drug is in a dissolution-retarded form and said cyclodextrin is in a dissolution-enhanced form.
4 . The composition of claim 1 or 3 wherein said dissolution-retarded form of said drug is a multiparticulate.
5 . The composition of claim 4 wherein said multiparticulate has a mean diameter of less than about 500 μm.
6 . The composition of claim 4 wherein said multiparticulate has a mean diameter of less than about 200 μm.
7 . The composition of claim I or 3 wherein said dissolution-retarded form of said drug comprises a coating.
8 . The composition of claim 2 or 3 wherein said dissolution-enhanced form of said cyclodextrin comprises said cyclodextrin having a mean particle size of less than about 125 μm.
9 . The composition of claim 2 or 3 wherein said dissolution-enhanced form of said cyclodextrin comprises said cyclodextrin in amorphous form.
10 . The composition of any of claims 1 - 3 wherein said composition provides within the first minute following administration to a use environment a molar ratio of dissolved cyclodextrin to dissolved drug that is greater than about one.
11 . The composition of claim 10 wherein said molar ratio of said dissolved cyclodextrin to said dissolved drug is at least about 1.5.
12 . The composition of claim 10 wherein said molar ratio of said dissolved cyclodextrin to said dissolved drug is at least about 2.
13 . The composition of claim 10 wherein said molar ratio of said dissolved cyclodextrin to said dissolved drug is at least about 3.
14 . The composition of claim 1 or 3 wherein said dissolution-retarded form provides a dissolved drug concentration about one minute after administration to a use environment that is less than 80% of the concentration of dissolved drug provided by a control composition consisting of crystalline drug.
15 . The composition of claim 2 or 3 wherein said dissolution-enhanced form of said cyclodextrin is at least 50% dissolved at one minute after administration to a use environment.
16 . The composition of claim 15 wherein said dissolution-enhanced cyclodextrin is at least 60% dissolved at one minute after administration to the use environment.
17 . The composition of any one of claims 10 , 14 and 15 wherein said use environment is an in vitro test solution comprising a 0.05M KH 2 PO 4 buffer solution.
18 . The composition of any one of claims 1 - 3 incorporated into a solid dosage form.
19 . The composition of claim 18 wherein said solid dosage form is chewable.
20 . The composition of any of claims 1 - 3 wherein said drug is selected from the group consisting of antacids, analgesics, anti-anginals, anti-anxiety agents, anti-arrhythmics, anti-bacterials, antibiotics, anti-diarrheals, anti-depressants, anti-epileptics, anti-fungals, anti-histamines, anti-hypertensives, anti-inflammatory agents, anti-virals, cardiac agents, contraceptives, cough suppressants, cytotoxics, decongestants, diuretics, drugs for genito-urinary disorders, drugs for use in parkinsonism and related disorders, drugs for use in rheumatic disorders, hypnotics, minerals and vitamins, lipid-lowering drugs and sex hormones.
21 . The composition of claim 20 wherein said drug is an anti-histamine comprising a benzhydrylpiperazine.
22 . The composition of claim 21 wherein said drug is cetirizine.