Opportunities in Analytical Approaches to Spray Drying of Solid Dosage Forms

Transcription

1 Opportuntes n Analytal Approahes to Spray Dryng of Sold Dosage Forms Dr. Renhard Vehrng Assoate Professor and George Ford Char n Materals Engneerng Unversty of Alberta, Department of Mehanal Engneerng 5-1G Mehanal Engneerng Buldng, Edmonton, AB, Canada T6G 2G8 Tel: , renhard.vehrng@ualberta.a MECHANICAL ENGINEERING Spray Dryng Proess Development by Tral and Error? There must be a better way. Outlne Atomzaton droplet formaton Expermental determnaton of droplet sze dstrbuton Theoretal desrptons Droplet sze Dstrbuton of suspended materal Droplet Evaporaton Numeral model Smplfed analytal desrpton Partle Formaton Predtng Sze Predtng Morphology Colleton and Outlet Condtons Cylone utoff Global mass and energy balane

2 Introduton: The Spray Dryng Proess Dryng Gas Gas Dryng Chamber Moleule Flter Exhaust Lqud Feed Atomzer Cylone Hammer / Jet Mllng Colletor Two-Flud Atomzers: Examples Laboratory sale (<0.6 kg/hr) ~6 n. Level 1 produton sale (< 6 kg/hr) Level 2 produton sale (< 60 kg/hr) How an the droplet sze dstrbuton be predted? Pneumat Atomzaton, Theory Mean dameter: d 2 ( v ) g A α m g + B m l β Depends on relatve veloty at nozzle head and the rato of the gas and lqud mass flows. A, B, α, β are funtons of the nozzle desgn and lqud propertes. Droplet sze dstrbutons for a spef nozzle need to be determned expermentally Masters, K.: Spray Dryng. CRC Press, Cleveland, 1972

3 Atomzer Testng Wth Phase Doppler Methods Atomzer Test Falty Provdes droplet sze dstrbutons for varous proess ondtons: 1 Normalzed Number Freq Droplet Dameter, mrons Snyder, et al., 12 th Annual Conf. on Lqud Atomzaton and Spray Systems. Indanapols, 1999 Spray Dryng of Suspensons Feedstok Atomzed Droplets (Blak box) How do partle sze dstrbuton and onentraton of suspended partles and atomzed droplet sze affet the omposton and partle sze dstrbuton of the fnal powder? Aerosol Stohast Model of Suspenson Atomzaton Ivey, J. W., Vehrng, R. AAPS Workshop on Utlzaton of Proess Modelng and Advaned Proess Control, Baltmore, 2009.

4 Example: Dstrbuton of Partles n Droplets Droplets: VMD: 9 µm, GSD 1.8 Suspended Partles: VMD: 4.6 µm, GSD 1.6 Conentraton: 2.45 g/l Probablty E-3 1E Partles per Droplet Example: Predton of Powder Propertes Fraton of Partles Propellant: VMD: 9 µm, GSD 1.8 Suspended Partles: VMD: 4.6 µm, GSD 1.6 Conentraton: 2.45 g/l Aerosol: VMD: 5.2 µm, GSD Partles per Aggregate Applaton Example: Porous Partles Wth Suspended Crystals Ivey, J. W., Vehrng, R. AAPS Workshop on Utlzaton of Proess Modelng and Advaned Proess Control, Baltmore, 2009.

5 Outlne Atomzaton droplet formaton Expermental determnaton of droplet sze dstrbuton Theoretal desrptons Droplet sze Dstrbuton of suspended materal Droplet Evaporaton Numeral model Smplfed analytal desrpton Partle Formaton Predtng Sze Predtng Morphology Colleton and Outlet Condtons Cylone utoff Global mass and energy balane Full Numeral Model Foss, W. R., Vehrng, R., 23rd Annual AAAR Conferene, Atlanta, GA, USA, Applaton Example: Surfae Enrhment of Proten ms PROTEIN WEIGHT FRACTION ms ms 0.6 SURFACE ms CONCENTRATION ms ms 0.2 INITIAL CONCENTRATION 45.1 ms ms RADIUS, mrons

6 More Pratal: Constant Rate Assumpton : Experment : Numeral Model : Constant Rate d 2 ( t) d κ t 2 0 Vehrng, R.: Partle Desgn usng Spray Dryng. The Fne Partle Soety, Int. Conf. on Bo and Pharm. Sene and Tehn., San Dego, Dmensonless Numbers: Pelet Number and Surfae Enrhment Pelet Number: κ Pe 8D Desrbes balane between veloty of surfae reesson and dffuson Surfae Enrhment: E s, m, Rato of surfae onentraton to average onentraton E 2 3 Pe Pe Pe Vehrng, R. Expert Revew: Pharmaeutal Partle Engneerng va Spray Dryng. Pharm. Res. 25: 999, How to Estmate Evaporaton Rate g Approxmaton: κ 8D ( Y ( T ) Y ) B Vapor Pressure: log P sat A T + C g l s e A B C T n K, P n Pa Wet bulb temperature: T wb 0.68 Tb 137 log( TG )

7 Even Smpler: Use Publshed Results Evaporaton Rate n µm 2 /ms Model Experment Gas Temperature n C (Dry) Droplet Temperature n C Droplet Temperature, 0 C 70 15% RH 60 10% RH 50 5% RH 40 2% RH 0% RH Gas Temperature, 0 C Vehrng, R., Foss, W. R., Lehuga-Ballesteros, D.: Partle Formaton n Spray Dryng. J. Aerosol Sene 38: 728, Charaterst Tmes: Droplet Dryng Tme Droplet dryng tme: 2 d0 τ D κ Can be used to estmate neessary resdene tme n dryer. Examples: a) Pulmonary drug delvery, atve not lable, d 0 5 µm, κ 5 µm 2 /ms: τ D 5 ms b) Nasal drug delvery, atve lable, d 0 30 µm, κ 2 µm 2 /ms: τ D 0.45 s Mass Balane Allows Predton of Sze 0,d 0 d p, p Geometr Dameter Aerodynam Dameter d p 3 d 6 a 0 d p 0 p 0 3 d * * 0

8 Predtng Partle Morphology: Sequene of Preptaton Dmensonless Number: S 0, 0, pre, Intal onentraton / Preptaton onentraton 2 Tme to preptaton: ( ) τ τ 3 D S0, E pre, 1 A B τ pre,a < τ pre,b τ pre,b < τ pre,a Predtng Partle Densty: Low Pelet Number Densty n g/m Trehalose Inlet Gas Temperature n C Low Pelet Number (<2) and hgh solublty lead to sold partles Predtng Partle Densty: Hgh Pelet Number Pe 2.7 Pe 5.6 Pe 12.5 Nanopartle Composte Partles Peptde Partles Vehrng, R., Foss, W. R., Lehuga-Ballesteros, D.: Partle Formaton n Spray Dryng. J. Aerosol Sene 38: 728, F. Iskandar et al. Journal of Collod and Interfae Sene 265, 296, J. S. Patton US Patent 6,685,967, 2004.

9 Cylone Separaton Cylone utoff (Leth / Lht model): d a,50 k 18µ d V 3 μ: Gas vsosty d : Cylone dameter V : Gas flow k: Confguraton fator d Cutoff needs to be verfed expermentally Global Mass and Energy Balane Dryng Gas Atomzng Gas Lqud Feed ATOMIZER CV DRYING CHAMBER Partles, Vapor, Gas CYCLONE Heat Loss PRODUCT COLLECTION Predton of Outlet Temperature (Graph removed) Measured and predted outlet temperatures agree wthn ± 2 C.

10 Predton of Powder Mosture Content Combnng outlet RH wth mosture sorpton data allows aurate estmate of powder mosture ontent (Graph removed) Conlusons The ndvdual steps of the spray dryng proess are farly well understood and an be desrbed theoretally. The spray dryng proess should be treated as a seres of subproesses. Expermental work should fous on the unknown aspets of the proess. Many proess and powder attrbutes an be predted and don t need to be determned emprally Usng analytal approahes to spray dryng saves tme and ost and allows theoretal dentfaton of key proess and formulaton varables leadng to prudent nvestment n proess ontrol measures. Dfferenes between observed and predted behavor pont to areas of future development and provde IP opportuntes. Outlook