Dry Powder for Inhalation
The aim of the invention is to improve the moisture resistance of dry powder formulations for inhalation which contain a pharmaceutically ineffective carrier of not-inhalable particle size and a finely divided pharmaceutically active compound of inhalable particle size and to also improve the storage stability of said formulations. To this end, magnesium stearate is used in said formulations. On of the features of the inventive dry powder is that a high fine particle dosage or fine particle fraction can be maintained also under relatively extreme temperature and humidity conditions.
1 . A dry powder inhaler, comprising
a) a powder reservoir containing a dry powder formulation having reduced moisture sensitivity comprising:
i) a pharmaceutically inactive carrier having particles of noninhalable particle size,
ii) a pharmaceutically active component comprising at least one finely divided pharmaceutically active compound having particles of inhalable particle size, and
iii) magnesium stearate; and
b) means for delivering metered doses of the pharmaceutically active compound for inhalation.
2 . The dry powder inhaler of claim 1 , wherein the pharmaceutically active compound is a hygroscopic compound capable of absorbing at least 0.5% by weight of its own weight of absorptively bound water when stored in air having a relative humidity of 50%.
3 . The dry powder inhaler of claim 1 , wherein the pharmaceutically active compound is a hydrophilic compound having a wetting angle of less than 90°.
4 . The dry powder inhaler of claim 1 , wherein the pharmaceutically active compound is a hydrophilic compound having a wetting angle of less than 70°.
5 . The dry powder inhaler of claim 1 , wherein the magnesium stearate is present in an amount of 0.1 to 2% by weight, based on the total weight of the formulation.
6 . The dry powder inhaler of claim 1 , wherein the magnesium stearate is present in an amount of 0.25 to 1% by weight, based on the total weight of the formulation.
7 . The dry powder inhaler of claim 1 , wherein the magnesium stearate is present in an amount of 0.4 to 0.8% by weight, based on the total weight of the formulation.
8 . The dry powder inhaler of claim 1 , wherein the carrier is selected from the group consisting of monosaccharides, disaccharides, sugar alcohols, polylactic acid and cyclodextrin.
9 . The dry powder inhaler of claim 1 , wherein the carrier is selected from the group consisting of glucose, lactose monohydrate and trehalose.
10 . The dry powder inhaler of claim 1 , wherein the formulation further comprises particles of micronized lactose monohydrate wherein at least 50% of the particles thereof have a maximum particle size of 10 μm.
11 . The dry powder inhaler of claim 1 , wherein the pharmaceutically active compound is formoterol or a pharmaceutically acceptable salt thereof.
12 . The dry powder inhaler of claim 1 , wherein the pharmaceutically active compound is selected from the group consisting of formoterol fumarate, formoterol tartrate, ipratropium bromide and tiotropium bromide.
13 . The dry powder inhaler of claim 1 , wherein the formulation further comprises a second pharmaceutically active compound having particles of inhalable size.
14 . The dry powder inhaler of claim 1 , wherein the pharmaceutically active component comprises
a) a member selected from the group consisting of formoterol fumarate, formoterol tartrate, levalbuterol sulfate and salmeterol xinafoate, and
b) a corticosteroid.
15 . The dry powder inhaler of claim 1 , said inhaler comprising a multidose reservoir.
16 . The dry powder inhaler of claim 1 , said inhaler comprising a dry powder predosed unit.
17 . The dry powder inhaler of claim 16 , wherein said predosed unit is in the form of a capsule.
18 . The inhaler of claim 1 , wherein said dry powder formulation of a) comprises a fine particle fraction (FPF), said formulation exhibiting a reduction in said FPF by at least 50% within 10 days of storage at 40° C. and 75% relative atmospheric humidity.