title: Physicochemical stability of crystalline sugars and their spray-dried forms: dependence upon relative humidity and suitability for use in powder inhalers.
abstract: Lactose, trehalose, sucrose, and mannitol were purchased in crystalline form and fractionated by sieving. Coarse (125-212 microns) and fine (44-74 microns) free-flowing fractions were selected as typical of drug carriers in dry-powder inhalers. In addition, one batch of each sugar was spray-dried to form a respirable powder (> 50% [w/w], < 5 microns). Both fractions and the spray-dried powders were characterized before and after storage for 30 days at < 23%, 23%, 52%, 75% and 93% relative humidity (RH) at 25 degrees C. Moisture uptake was determined by thermogravimetric analysis (TGA) validated by Karl Fischer titration. Sieve fractions (before storage at different RHs) and spray-dried materials (before and after storage) were further characterized by differential scanning calorimetry (DSC) and x-ray powder diffraction (XRPD). All crystalline sieve fractions (except sucrose at 93% RH) were stable at 25 degrees C and showed insignificant moisture uptake when exposed to each relative humidity for 30 days. Sucrose dissolved in sorbed moisture at 93% RH. Spray-dried lactose, sucrose, and trehalose, which were collected in the amorphous form, showed moisture uptake, without recrystallization, when held for 30 days at 23% RH. These sugars recrystallized as sintered masses and became undispersible at > or = 52% RH. Spray-dried mannitol was apparently 100% crystalline when collected directly from the spray-dryer; it did not show humidity-induced changes. The physicochemical behavior of each sugar form is discussed as it relates to the sugar's suitability as a powder-inhaler excipient, with both conventional and protein drugs.
authors.affiliation: Barr Laboratories, Inc. Pomona, New York 10970, USA.
authors.forename: V
authors.initials: V
authors.lastname: Naini
authors.forename: P R
authors.initials: PR
authors.lastname: Byron
authors.forename: E M
authors.initials: EM
authors.lastname: Phillips
mesh_terms: D002152:Calorimetry, Differential Scanning; D002241:Carbohydrates / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D006813:Humidity; D007785:Lactose / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D009330:Nebulizers and Vaporizers; D011312:Pressure; D013395:Sucrose / Q000737:chemistry; D013696:Temperature; D014199:Trehalose / Q000737:chemistry
chemical_list: D002241:Carbohydrates; D005079:Excipients; D008353:Mannitol; D013395:Sucrose; D014199:Trehalose; D007785:Lactose