Complete systems for recipe development

With its tai­lor-made turnkey tech­no­log­i­cal solu­tions based around the ZSK twin screw extrud­er, Cope­ri­on is respond­ing to the grow­ing demand from the phar­ma­ceu­ti­cal indus­try for sys­tems for con­tin­u­ous pro­duc­tion process­es that offer high­er effi­cien­cy and uni­for­mi­ty than batch process­es. One exam­ple of this is a com­plete phar­ma­ceu­ti­cal sys­tem with a ZSK 18 MEGA­l­ab twin screw extrud­er with an 18 mm screw diam­e­ter that was recent­ly deliv­ered to an inter­na­tion­al phar­ma­ceu­ti­cal com­pa­ny. This ful­ly inte­grat­ed sys­tem includes two Cope­ri­on K‑Tron gravi­met­ric loss-in-weight feed­ers with supe­ri­or accu­ra­cy in API and liq­uid feed­ing, a cool­ing belt, and a Cope­ri­on Pel­letiz­ing Tech­nol­o­gy strand pel­letiz­er. With a max­i­mum through­put rate of 10 kg/h, it is suit­able for both wet extru­sion and con­tin­u­ous hot-melt extru­sion (HME) on a lab­o­ra­to­ry scale. In the imple­men­ta­tion of this sys­tem, Cope­ri­on lever­aged its expe­ri­ence that spans over 30 years in spe­cial­ty appli­ca­tions for recipe devel­op­ment as well as large pro­duc­tion sys­tems for this demand­ing indus­try. April 17–19, 2018 Cope­ri­on presents its tech­no­log­i­cal solu­tions at Inter­phex 2018 (New York, NY, USA, Booth 2261).

Precise, reproducible product quality

One rea­son for the con­tin­u­al­ly increas­ing impor­tance of HME pro­cess­ing in the phar­ma­ceu­ti­cal indus­try is its inten­sive mix­ing effect, as offered by Coperion’s co-rotat­ing ZSK twin screw extrud­ers. As a result, active sub­stances and excip­i­ents can be dis­persed very fine­ly and homo­ge­neous­ly in phar­ma­ceu­ti­cal poly­mers with­out the use of sol­vents, which pro­motes a high degree of bioavail­abil­i­ty of the APIs (also BCS class­es 2 & 4). In addi­tion, the self-wip­ing screw pro­file of these sys­tems elim­i­nates dead spaces. Due to the spe­cif­ic torque of 11.3 Nm/cm3 which allows low ratios of through­put to screw speed, the ther­mal stress on the APIs and poly­mers in the ZSK process sec­tion is low. Com­bined with the cus­tomized periph­er­al equip­ment, these sys­tems make it pos­si­ble to pre­cise­ly adhere to the recipe and to cre­ate a repro­ducibly high prod­uct qual­i­ty. In addi­tion, process steps, such as encap­su­la­tion or taste mask­ing, can be inte­grat­ed into the process.

Highly accurate and customized feeding of the ingredients

The inte­gra­tion of the Cope­ri­on K‑Tron feed­ers for com­plete sys­tems ensures opti­mal dis­pens­ing of the for­mu­la­tion ingre­di­ents. Cope­ri­on K‑Tron is known for its high­ly accu­rate feed­ing solu­tions for phar­ma­ceu­ti­cal appli­ca­tions. The feed­ers, which are avail­able as vol­u­met­ric or gravi­met­ric mod­els, demon­strate a high lev­el of reli­a­bil­i­ty, espe­cial­ly in con­tin­u­ous process­es. The wide range of feed­er designs makes it pos­si­ble to feed a very wide range of mate­ri­als – from the finest pow­ders and pel­lets to liq­uids and pastes – to a phar­ma­ceu­ti­cal process very pre­cise­ly. Suit­able feed sys­tems are even avail­able for ingre­di­ents with demand­ing prop­er­ties, such as poor­ly flow­ing or sticky mate­ri­als, flood­ing pow­ders, tem­per­a­ture-sen­si­tive liq­uids, or sub­stances with a high haz­ard poten­tial. For com­plex recipes, sev­er­al feed­ers can be grouped around an extrud­er inlet.
At this year’s Inter­phex, Cope­ri­on K‑Tron is pleased to dis­play the newest inno­va­tion in phar­ma­ceu­ti­cal feed­er design. The new feed­er and scale com­bi­na­tion includes mod­u­lar­i­ty for quick feed­er exchange, eas­i­er access and clean­abil­i­ty, as well as a small­er foot­print, ide­al for mul­ti feed­er clus­ter­ing around con­tin­u­ous processes.
All Cope­ri­on K‑Tron feed­ers have always been specif­i­cal­ly designed to meet the strin­gent require­ments of this indus­try, includ­ing com­pli­ance with GMP guide­lines and the use of FDA-approved con­struc­tion materials.

Modular system provides maximum flexibility

All ZSK phar­ma­ceu­ti­cal extrud­ers have a com­pact design, are easy to oper­ate, and offer opti­mal acces­si­bil­i­ty for clean­ing and main­te­nance. For max­i­mum flex­i­bil­i­ty when feed­ing liq­uids and devolatiliz­ing the melt, Cope­ri­on uses a mod­u­lar design for the process sec­tion, which includes sev­er­al bar­rels in which the co-rotat­ing screws oper­ate. The size-inde­pen­dent Do/Di ratio (out­er screw diam­e­ter to inner screw diam­e­ter) of 1.55 allows reli­able scale-up. The sys­tems are designed to com­ply with GMP guide­lines. Cus­tomers receive com­plete doc­u­men­ta­tion for all process para­me­ters (V‑Lifecycle) based on a URS (User Require­ment Specification).

Precise pelletizing solutions

Cope­ri­on Pel­letiz­ing Tech­nol­o­gy offers suit­able pel­letiz­ers that are specif­i­cal­ly designed for phar­ma­ceu­ti­cal appli­ca­tions. The sys­tems are char­ac­ter­ized by their high lev­el of reli­a­bil­i­ty and prod­uct qual­i­ty and have proven them­selves many times in prac­tice. Appro­pri­ate mate­ri­als and sur­faces are used in order to meet the high require­ments of the phar­ma­ceu­ti­cal indus­try. Spe­cial atten­tion is paid to mak­ing the sys­tems easy to access and to clean. Oth­er fea­tures, such as pel­let length adjust­ment, can also be realized.
Ste­fan Geb­hardt, Gen­er­al Man­ag­er of Busi­ness Unit Food & Phar­ma at Cope­ri­on, says: “Like all indus­tries, the phar­ma­ceu­ti­cal indus­try is con­stant­ly striv­ing to increase process effi­cien­cy. Our con­tin­u­ous­ly oper­at­ing ZSK extru­sion sys­tems offer inter­est­ing poten­tial, as they increase pro­duc­tiv­i­ty in com­par­i­son to con­ven­tion­al batch process­es with­out com­pro­mis­ing on qual­i­ty, and they require less space. The FDA also sup­ports the trend towards con­tin­u­ous process­es because they can accel­er­ate prod­uct devel­op­ment and reduce pro­duc­tion time. And, as the last link in the chain, patients also ben­e­fit from the use of our extrud­ers because the inten­sive dis­pers­ing effect can increase the bioavail­abil­i­ty of the incor­po­rat­ed phar­ma­ceu­ti­cals, and there­fore opti­mize the effect.”