High-quality continuous production: differentiated process checks thanks to inline particle measurement

 To ensure con­sis­tent, high-qual­i­ty pro­duc­tion results, con­stant mea­sure­ments and checks dur­ing pro­cess­ing are indis­pens­able. Since tak­ing sam­ples and eval­u­at­ing them in the lab­o­ra­to­ry is labo­ri­ous, time-con­sum­ing and pro­vides only spot checks with a time delay, inline mea­sure­ment is par­tic­u­lar­ly impor­tant pre­cise­ly in these pro­duc­tion areas: the process­es can be checked at any time and adjust­ed if nec­es­sary. This is why IPC Process-Cen­ter GmbH & Co. KG, a Glatt-group com­pa­ny man­u­fac­tur­ing inno­v­a­tive gran­ules and pel­lets for the phar­ma­ceu­ti­cal and food indus­tries, uses Par­sum GmbH inline par­ti­cle probes for con­tin­u­ous­ly mon­i­tor­ing their sen­si­tive process­es. The mea­sur­ing accu­ra­cy of the IPP 70‑S and IPP 70-Se probes means that the par­ti­cle-size dis­tri­b­u­tions of inter­me­di­ate and end prod­ucts are con­stant­ly mon­i­tored, so that flex­i­bly adjust­ed and opti­mised process­es can be con­trolled pre­cise­ly and repro­ducible qual­i­ty can be guar­an­teed. Opti­mal process man­age­ment and the avoid­ance of pro­duc­tion errors and entire off-spec batch­es mean that con­sid­er­able finan­cial sav­ings can be achieved. 

“The instal­la­tion of the two new inline probes gives us the advan­tage that the man­u­fac­tur­ing process can be mon­i­tored con­tin­u­ous­ly and thus process safe­ty is great­ly improved,” explains Jan Demi­an, the pro­duc­tion-plan­ning engi­neer respon­si­ble for mea­sure­ment tech­nol­o­gy and data eval­u­a­tion at IPC Process-Cen­ter GmbH & Co. KG. “Fur­ther­more, the work­load for sam­pling and analy­sis is much low­er than with pre­vi­ous process mon­i­tor­ing using screen analy­sis, and the unin­ter­rupt­ed data can be eval­u­at­ed and assessed right up to the end of the cam­paign.” How­ev­er, pre­cise mea­sure­ment val­ues are also essen­tial dur­ing the dif­fi­cult pre-pro­duc­tion phase in order to car­ry out fine adjust­ment of all the para­me­ters and to start the process correctly.

Par­sum mea­sure­ment tech­nol­o­gy was installed in a Glatt 250 (GFG 250) flu­idised-bed gran­u­la­tor, which can be con­vert­ed into a Pro­Cell spout­ed bed by adding a fur­ther pro­cess­ing unit. 

The process cham­ber of the GFG 250 is approx­i­mate­ly 3.5 m long, 0.8 m wide and 0.7 m high. The hold-up is between 200 and 700 kg, depend­ing on the prod­uct and method. 

The process cham­ber of the GFG 250 is approx­i­mate­ly 3.5 m long, 0.8 m wide and 0.7 m high. “The desired charge quan­ti­ty, what we call the ‘hold-up’, depends on the prod­uct and the process and is between 200 and 700 kg,” says Demi­an. IPC uses this com­plete­ly con­tin­u­ous­ly oper­at­ing sys­tem main­ly for the spray gran­u­la­tion of liq­uids and the agglom­er­a­tion of pow­ders. For the lat­ter case, the start­ing mate­r­i­al is fed con­tin­u­ous­ly into the process cham­ber and a binder solu­tion is sprayed through dual-flu­id noz­zles sit­u­at­ed in the floor. “The aim is to bring togeth­er indi­vid­ual par­ti­cles of start­ing mate­r­i­al using the adhe­sive prop­er­ties of the binder to form larg­er agglom­er­a­tions until the desired par­ti­cle-size dis­tri­b­u­tion is reached,” explains Demi­an. 

Instal­la­tion of the IPP 70-Se and IPP 70‑S probes 

The probes can be used to mon­i­tor the growth in par­ti­cle size in real time. The ATEX-cer­ti­fied IPP 70-Se probe has been installed direct­ly in the process cham­ber for in-process checks and tracks the course of the process by con­stant­ly mon­i­tor­ing the gran­u­la­tion. 

Flu­idised-bed and oth­er process­es can be devel­oped and improved more quick­ly using process-ana­lyt­i­cal tech­nol­o­gy (PAT). For instance, direct mea­sure­ment in the flu­idised bed makes it pos­si­ble to adjust the appro­pri­ate para­me­ters where need­ed to opti­mise the process and ful­ly exploit the potential

of the pro­duc­tion plant. In this way, the amount of mate­r­i­al cir­cu­lat­ing in the adjoin­ing screen­ing and grind­ing cir­cuit can also be con­sid­er­ably reduced. 

The IPP 70‑S is used to mon­i­tor the tar­get frac­tion down­stream of the clas­si­fy­ing screen and is sit­u­at­ed direct­ly behind the clas­si­fi­er at the out­let. The ATEX-cer­ti­fied IPP 70-Se has been installed direct­ly in the process cham­ber for in-process checks and tracks the course of the process by con­stant­ly mea­sur­ing the par­ti­cle-size dis­tri­b­u­tion. 

Source: Par­sum Gesellschaft für Partikel‑, Strö­mungs- und Umweltmesstech­nik mbH 

The sec­ond probe, of the IPP 70‑S type, is used to mon­i­tor the tar­get frac­tion down­stream of the clas­si­fy­ing screen and is sit­u­at­ed direct­ly behind the clas­si­fi­er at the prod­uct out­let. At this mea­sure­ment point, the par­ti­cle-size dis­tri­b­u­tion of the spec­i­fied prod­uct is checked and imme­di­ate­ly approved if all require­ments are met. Mal­func­tions of the clas­si­fi­er or a bro­ken screen can be detect­ed here straight away, so the per­son­nel respon­si­ble can take suit­able steps quick­ly and accu­rate­ly. “If the probe is used inline, the mea­sure­ment results are avail­able imme­di­ate­ly and the con­tin­u­ous dis­play of the par­ti­cle-size curve shows how the process is cur­rent­ly run­ning,” says Ste­fan Diet­rich, Parsum’s man­ag­ing direc­tor. “For the oper­a­tor, the mea­sure­ment forms a sort of win­dow allow­ing a direct insight into the process.” Nor­mal­ly, the batch is checked by means of mul­ti­ple spot checks dur­ing the process. Mea­sure­ment at the out­let, and the asso­ci­at­ed para­met­ric approval in par­tic­u­lar, con­sti­tutes a com­plete­ly new approach for the phar­ma­ceu­ti­cal indus­try. 

Upgrad­ing to the new D24 dis­pers­er 

In addi­tion to the probes, IPC also uses a new­ly devel­oped 

D24 dis­pers­er, with which the ser­vice time between the nec­es­sary clean­ing oper­a­tions was rad­i­cal­ly improved. The inline dis­pers­er ensures that the

par­ti­cles are iso­lat­ed for mea­sure­ment even under the dif­fi­cult con­di­tions in the flu­idised bed. Even moist or sticky mate­ri­als and sub­stances with high pro­por­tions of fines can be mea­sured reli­ably, which would not be pos­si­ble with­out dis­per­sion. “With the pre­vi­ous mod­el, the D23, prod­uct con­stituents would accu­mu­late on the dis­pers­er after a while when mea­sur­ing direct­ly in the flu­idised bed. Since the probe is not acces­si­ble for clean­ing dur­ing oper­a­tion, it was not pos­si­ble to con­tin­ue mea­sur­ing the par­ti­cle size with­out inter­rupt­ing the process,” explains Demi­an. Chang­ing to the new D24 rec­ti­fied these prob­lems, and process times of up to two weeks with­out clean­ing and with con­tin­u­ous data record­ing by the IPP 70-Se probe could be achieved. 

Spe­cial tech­nol­o­gy from Par­sum was installed in a Glatt 250 (GFG 250) flu­idised-bed gran­u­la­tor, which can be con­vert­ed into a Pro­Cell spout­ed bed by adding a fur­ther pro­cess­ing unit. IPC uses this com­plete­ly con­tin­u­ous­ly oper­at­ing sys­tem main­ly for the spray gran­u­la­tion of liq­uids and the agglom­er­a­tion of pow­ders. 

Source: IPC Process-Cen­ter GmbH & Co. KG 

IPC is very hap­py with the use of the Par­sum probes: “The con­tin­u­ous check­ing and mon­i­tor­ing of par­ti­cle size dur­ing the process allows us to adjust the process para­me­ters accord­ing to the desired tar­get spec­i­fi­ca­tion so as to achieve an opti­mal result,” says Demi­an. “By mon­i­tor­ing the tar­get frac­tion, we can detect devi­a­tions from the desired result ear­ly and react quick­ly to pro­tect the process.”

Cur­rent project: Imple­men­ta­tion of Par­sum View 3.0 soft­ware 

A cur­rent project aim to put GMP’s Par­sum View 3.0 soft­ware, which makes mea­sure­ment data cen­tral­ly acces­si­ble, into oper­a­tion at the Dres­den com­pa­ny. This soft­ware pro­vides very user-friend­ly man­age­ment of for­mu­la­tions, batch­es and users, and an audit trail that records all oper­a­tor inter­ac­tions. In the process, the pro­gram stores data direct­ly in an SQL data­base. The data is there­fore tam­per­proof and sat­is­fies the guide­lines of the Amer­i­can Food and Drug Admin­is­tra­tion (FDA). “Although we use the sys­tem local­ly, it can be accessed from any autho­rised work­sta­tion via a net­work,” says Demi­an con­fi­dent­ly. The Par­sum-View add-on has been devel­oped specif­i­cal­ly for the phar­ma­ceu­ti­cal sec­tor, meets the high­est secu­ri­ty demands and com­plies with the require­ments of 21 CFR 11. 

IPC has signed a main­te­nance con­tract with Par­sum, which means that the com­pa­ny can also ben­e­fit from an inspec­tion of the mea­sure­ment probes with the annu­al Oper­a­tional Qual­i­fi­ca­tion, ensur­ing high sys­tem avail­abil­i­ty.