Pearlitol 160 c

Pearlitol^® 200SD and Pearlitol^® 160C were obtained from Roquette, Lestrem, France. Micronized salbutamol sulphate (SS) and budesonide (BUD) were supplied from Fagron, Bologna, Italy and by Chiesi Farmaceutici, Parma, Italy respectively. Lacto-Sphere^® MM50 (sieved α-lactose monohydrate, d_V50 = 53.1 μm) was provided by Micro-Sphere SA (Monteggio, Switzerland). The excipients for the recrystallization phase of mannitol were PVP K30 (Kollidon^® 30, BASF, Ludwigshaufen, Germany), PVA 22K (Fluka, Buchs, Switzerland) and CaCl₂ (Merck, Darmstad, Germany). The analytical method was conducted using acetonitrile (VWR, Milan, Italy) and methanol (VWR, Milan, Italy). The mobile phase and buffer solutions were prepared using K₂HPO₄ and KH₂PO₄ (both from ACEF, Fiorenzuola, Italy). A 0.45 µm PTFE filter membrane was used (ALBET^®, Madrid, Spain).

β mannitol (Pearlitol^® 160C) was acquired from Roquette Frères (Lestrem, France), and δ mannitol (Parteck^® Delta M) and spray granulated β mannitol (Parteck^® M200) were supplied by Merck KGaA (Darmstadt, Germany). Magnesium stearate was purchased from Peter Greven (Bad Münstereifel, Germany). All powders were sieved through a 1 mm sieve using a Turbosieve BTS 100 (L.B. Bohle, Ennigerloh, Germany) with a speed of 355 rpm. The influence of initial powder particle size on granules and tablet properties was investigated by comparison of two different particle size distributions of β mannitol powder: the initial 1 mm turbosieved powder and a fraction smaller than 180 µm of the β mannitol (180 β mannitol) powder. Therefore, after sieving with the turbosieve, a fraction of Pearlitol^® 160C powder was again manually sieved through a sieve with a mesh size of 180 µm (Retsch GmbH, Haan, Germany) before further processing.

PEO [PolyOx® WSR N-10 (PEO N-10), MW: 100 000 Da; PubChem CID: 5327147] and Duolite^TM AP 143/1083 (Cholestyramine Resin USP; PubChem CID: 70695641) were kindly donated by Dow Chemical Company (Midland, MI). DFS (PubChem CID: 5018304) was purchased from Sigma Aldrich (St. Louis, MO). Pearlitol® 160 C was obtained from Roquette Pharma as gift sample. DFS 0.1% w/v ophthalmic solution (Akorn Pharmaceuticals, Lake Forest, IL) was purchased from the pharmacy. All other chemicals were purchased from Fisher Scientific (St. Louis, MO).