Dry Powder For Inhalation
The present invention provides dry powder formulations for inhalation having improved moisture resistance such that the powders maintain a high fine particle dosage or fine particle fraction following storage under relatively extreme temperature and humidity conditions.
1 . A dry powder inhaler, comprising
a) a multidose powder reservoir containing a dry powder 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 as a pulverulent material present in an amount of 0.5 to 5% by weight, based on the total weight of the formulation; and
b) means for delivering metered doses of the pharmaceutically active compound for inhalation,
wherein said dry powder has a fine particle fraction (FPF) and a fine particle dose (FPD), said powder exhibiting improved stability of FPF and FPD following 4 to 10 days of storage at 40° C. and 75% relative atmospheric humidity compared to a reference lacking magnesium stearate as a pulverulent material.
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 0.5% to 0.75% by weight, based on the total weight of the formulation.
6 . 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.
7 . The dry powder inhaler of claim 1 , wherein the carrier is selected from the group consisting of glucose, lactose monohydrate and trehalose.
8 . 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 um.
9 . The dry powder inhaler of claim 1 , wherein the pharmaceutically active compound is formoterol or a pharmaceutically acceptable salt thereof.
10 . 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.
11 . The dry powder inhaler of claim 1 , wherein the powder further comprises a second pharmaceutically active compound having particles of inhalable size.
12 . 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.
13 . The inhaler of claim 1 , wherein the pharmaceutically active component does not comprise salbutamol sulfate, salmeterol xinafoate, or beclomethasone dipropionate.