The pharmaceutical industry has invested large amount

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1 Proceedngs of the Internatonal MultConference of Engneers and Computer Scentsts 0 Vol II, IMECS 0, March -, 0, Hong Kong Improvng Performance of Tabletng Process Usng DMAIC and Grey Relaton Analyss Abbas Al-Refae, Mng-Hsen L, Issam Jalham, Nour Bata, and Kawther Al-Hmadeen Abstract Ths research mplements the well-known sx sgma approach defne-measure-analyze-mprove-control (DMAIC) to mprove the performance of drect compresson process wth two qualty responses; tablet s weght and hardness. At current factor settngs, the x and s charts are judged n-control for both responses. However, the process was found capable for hardness but ncapable for weght. Three process factors are nvestgated, ncludng machne speed (S), compresson force (F), and fllng depth (D). The Taguch s L array s adopted to nvestgate the effects of the three process factors concurrently. Then, the grey relatonal analyss based rankng s mplemented to determne the combnaton of optmal factor levels, whch s found as SFD. Intally, the process capablty values for hardness and weght are. and are 0.8, respectvely. The multvarate capablty ndex, MC pk, s calculated and found 0.8. After process mprovement, the process capablty values are found equals to. and The MC pk s enhanced to.68. In concluson, the DMAIC approach s found effectve for mprovng the performance of drect compresson process wth tablet s weght and hardness. Index Terms Drect compresson, Grey analyss, Process capablty, Taguch method The Taguch method s wdely appled because of ts proven success n mprovng the qualty of manufactured products n many busness applcatons. Nevertheless, t has been only found effcent for optmzng a sngle qualty response Nevertheless, t has been only found effcent for optmzng a sngle qualty response [4-6]. In contrast, the grey relatonal analyss based on the grey system theory [] can be utlzed for solvng complcated nterrelatonshps among multple qualty responses [8, ]. Therefore, ths research utlzes DMAIC methodology to enhance the performance of the tablets drect compresson process utlzng grey relaton analyss. Ths paper s organzed as follows. Secton two presents the DMAIC approach. Secton three summarzes research results. Fnally, secton four summarzes conclusons. II. IMPLEMENTING DMAIC APPROACH The DMAIC approach s mplemented as presented n the followng subsectons. A. Defne the mportance qualty responses The drect compresson of tablets s llustrated n Fg.. I. INTRODUCTION The pharmaceutcal ndustry has nvested large amount of resources n mprovng the performance of drect compresson process []. Tablet defects result n huge busness losses due to ther nfluence on human health. Among the key qualty responses are tablet hardness and weght. Varaton n these two responses leads to rejecton of tremendous tablet quanttes. Among the proven approaches for mprovng qualty and productvty s the defne-measure-analyze-mprove control (DMAIC) approach, whch has been mplemented wdely to mprove performance n many ndustral applcatons [,]. Manuscrpt receved Nov., 0; revsed Jan., 0. Ths work was supported by the Unversty of Jordan, Amman. A. Al-Refae s wth the Department of Industral Engneerng, Unversty of Jordan, Amman, 4, Jordan (e-mal: abbas.alrefa@ju.edu.jo). M. H. L s wth the Department of Industral Engneerng and Systems Management, Feng Cha Unversty, Tachung, Tawan (e-mal: mhl@fcu.edu.tw). Issam Jalham s wth the Department of Industral Engneerng, Unversty of Jordan, Amman, Jordan. E-mal: jalham@ju.edu.jo N. Bata s wth the Department of Industral Engneerng, Unversty of Jordan, Amman, 4, Jordan. K. Al-Hmadeen s wth the Department of Industral Engneerng, Unversty of Jordan, Amman, 4, Jordan. ISBN: ISSN: (Prnt); ISSN: (Onlne) Fg.. Process mappng. The Tablet qualty depends on two man qualty responses ncludng hardness and weght. The hardness lower and upper specfcatons lmts of the AM-tablets are 0 and 60 measured by Newton (N), respectvely. It s requred that tablet hardness to be the larger the better wthn these specfcatons. The second mportant qualty response s the tablet weght. The upper and lower specfcaton lmts of the tablet average weght are.0 ± 4. mg. The tablet hardness and weght are consdered the larger-the-better (LTB) and nomnal-the-best (NTB) qualty types, respectvely. B. Measurng the performance of tablet s producton lne A control chart s one of the prmary technques of statstcal process control. The chart has a centre lne (CL) and the upper and lower control lmts represented by UCL and LCL, respectvely. The CL represents where ths process characterstc should fall. A wdely mplemented control charts for montorng response mean and varablty are the x and s charts. Twenty fve samples, each sample IMECS 0

2 Proceedngs of the Internatonal MultConference of Engneers and Computer Scentsts 0 Vol II, IMECS 0, March -, 0, Hong Kong wth sample sze of ten tablets, are taken after the process s stable. The x and s control charts for hardness are constructed then depcted n Fg.. The LCL, CL, and UCL for x chart are calculated.44, 4.4, and.60, respectvely. Whle, the LCL, CL, and UCL for the s chart are estmated 0.8,.40, and.0, respectvely. Smlarly, the x and s control charts for the unt average weght are establshed as shown n Fg.. The LCL, CL, and UCL for x chart are found equal to 4.84, 6.46, and 8., respectvely. Whle, the LCL, CL, and UCL for the s chart are of values 0.46,.66, and.8, respectvely. Observng Fgs. and, nor ponts fall outsde the control lmts nether sgnfcant pattern s found. Consequently, the process s concluded operatng n a statstcal control state for the two measured values. A vtal part of an overall qualty-mprovement program s process capablty analyss by whch the capablty of a manufacturng process can be measured and assessed. In practce, the process standard devaton,, s unknown and frequently estmated by: s () c 4 where c 4 s a constant related to sample sze, whle s s the CL value n s chart. The estmator of C pk, C ˆ, s pk expressed mathematcally by: ˆ USL ˆ ˆ LSL Cpk mn, () For larger-the-better response, the C ˆ pk s calculated as: ˆ ˆ LSL Cpk () where ˆ s the estmated mean, whch s the equals to x ; the CL value of x chart. In ths research, the recommended mnmum value of the process capablty rato s.4, due to safety, strength, or crtcal parameter for an exstng process [0]. In ths research, the mnmal requred process capablty values for hardness and weght are.4 and.00, respectvely. From Fg., the s value for average hardness s calculated.40 and the c value for a sample sze of 0 s 0.. Substtutng s and c4 values n Eq. (), the ˆ s equal to.8. Introducng x of 4.4 n Eq. (), the Cˆ pk s calculated and found equals.. Compared wth the recommended mnmum value (=.4), t s concluded that process s almost capable for average tablet s hardness. Smlarly, the process capablty s estmated for average unt weght. From Fg., the s value s calculated.66. Then, ˆ s calculated and found equals.. Usng Eq. (), the Cˆ pk s 0.8, whch s much less than the mnmum value (=.00) and hence ndcates that the process s ncapable. A crteron for selectng an optmal desgn s developed and called MCpk to be used as a capablty measure for a process havng multple performance measures []. In ths research, the MCpk s calculated as: 8 UC L=.60 Mean 6 4 X=4.4 LC L=.44 UC L=.0 StDev 4 S=.40 LC L=0.8 Fg.. The x - s control charts for hardness. 8 UC L=8. Mean 6 X=6.46 LC L=4.84 UC L=.8 StDev S=.66 LC L=0.46 Fg.. The x - s control charts for weght. ISBN: ISSN: (Prnt); ISSN: (Onlne) IMECS 0

3 Proceedngs of the Internatonal MultConference of Engneers and Computer Scentsts 0 Vol II, IMECS 0, March -, 0, Hong Kong C pk MCpk (4) Utlzng the obtaned process capabltes for averages of hardness and weght ( C ˆ pk =.46; C ˆ pk = 0.8), the MCpk s calculated and found 0.8. Typcally, the MCpk value larger than one ndcates capable process wth multple responses. Accordngly, the tablet compresson process s concluded ncapable. C. Analyzng and mprovng the performance of tablet s producton process C.. Analyzng process performance Based on prevous studes [-4] and process knowledge, the most mportant controllable factors are: compresson force (N), fllng depth (mm), and machne speed (stroke/hr). Process experts recommend that each factor s assgned three-physcal value levels as shown n Table I. In ths method, an orthogonal array (OA) s utlzed to nvestgate several process factors concurrently at permssble relablty and at low cost. For compresson process under study, the approprate Taguch s OA for nvestgatng three factors wth ther correspondng twoway nteractons s the L array. Table I Control factors settngs. Control factor Level Machne speed (S,0 Tab/hr) Compresson Force (N) Fllng Depth (mm) The desgned experments were carred out on a hgh capacty rotary press machne of the type Manesty wth the known propertes of the tablet s formulaton powder mxture. Two repettons were performed for each experment. Each repetton conssts of 0 tablets. The hardness and weght tests were carred out usng Unt Tester PTB Pharma Test nstrument and Mettler Toledo balance Model PR 0DR, respectvely. The expermental results of the tablet hardness and weght of the two replcates, R and R, respectvely, are dsplayed n Table II. C.. Improvng process performance The grey relatonal analyss s adopted for mprovng the performance of tablet s drect compresson process wth two qualty response; the averages of tablet hardness and weght, as descrbed n the followng steps: Step : The Taguch method employs a sgnal-to-nose rato (SNR) to measure the present varaton. The defnton of SNR dffers accordng to the qualty response type. Typcally, larger SNR ndcates better performance. The SNR for the averages of hardness and weght, and, respectvely, are estmated as follows k 0log( ), =,,..., () yr 0 log, =,,..., (6) k r y s where k represents the number of replcates. To avod the effect of adoptng dfferent unts of the two qualty responses, the and are normalzed. Let and denote the normalzed and, respectvely. Calculated respectvely as: mn,,,..., () mn mn mn,,,..., where mn{ } and { } are the smallest and the largest value of, respectvely. Smlarly, the mn { } and { } are the smallest and the largest value and, respectvely, from all experments for each response. Step : Calculate the grey relatonal coeffcent, (, ) and (, ), respectvely as follows: o o (, ), =,,..., mn o o() Smlarly: (, ), =,,..., (0) mn o o() where ξ s the dstngushng coeffcent, whch defned n the range of zero and one and t s commonly set 0.. The () o and () o are the absolute devatons of the and from the reference sequences 0and 0 of the averages of tablet hardness and weght, calculated respectvely usng: ( ), =,,..., () o o (8) () and ( ), =,,..., () o o The and mn represent the smallest oj () and the largest oj () for all the experments from both qualty responses, respectvely. Step : Generate the average grey relatonal grade,, usng j, =,,..., () j Step 4: Let lf denotes the average of values at level l of factor f. Calculate the lf values for all factor levels. Then, ISBN: ISSN: (Prnt); ISSN: (Onlne) IMECS 0

4 Proceedngs of the Internatonal MultConference of Engneers and Computer Scentsts 0 Vol II, IMECS 0, March -, 0, Hong Kong decde the optmal level for each factor f as the level that mzes lf for ths factor. In some cases, the optmal factor levels are close to each that makes level selecton not be easly determned based on lf. In ths case, the ordnal value s to rank the values n an ascendng order, where the lowest receves a rank of one. Identfy the combnaton of optmal factor levels utlzng the ordnal values. Let SOV fl be the sum of the ordnal values for level l of factor f. The hgher the SOV fl mples better process performance. Then the optmal factor level, l, of factor f s the level that mzes the value of SOV, that s, fl l l SOV, f (4) l fl Applyng the above procedure, the results of grey relatonal coeffcents and grades are dsplayed n Table III. The values are calculated then summarzed n Table IV. lf Observng the lf values of the fllng depth factor, t s noted that the D and D values are almost equal. Hence, the SOV fl values are calculated then also shown n Table III. The SOV fl values are fnally adopted to dentfy optmal factor levels. In Table IV, t s found that the combnaton of the optmal factor levels s S P D. Gven the c 4 value for a sample sze of 0 s 0.. The ˆ values for hardness and weght are calculated.0 and., respectvely. The correspondng Cˆ pk values are found equals to. and The correspondng MCpk equals.68, whch ndcates great savngs n manufacturng and qualty costs. D. Control process performance Confrmaton experments are conducted at S P D to check the acheved mprovement. Fgs. 4 and depct the confrmaton x -s charts for the average hardness and weght, respectvely. The two control charts are n statstcal control and thus can be used for montorng and controllng the future producton batches. Fg. 4 also depcts the x and s control charts for average hardness from confrmaton experments. It s noted that the UCL, CL, and LCL for x chart are calculated.4, 48.8, and , respectvely. Whle, the UCL, CL, and LCL for the s chart are estmated 4.844,.8, and 0.80, respectvely. On the other hand, the x and s control charts for the weght are establshed as shown n Fg.. The UCL, CL, and LCL for x chart are found equal to.6, 4.04, and., respectvely. Whle, the UCL, CL, and LCL for the s chart are of values.4,.4, and 0.84, respectvely. III. CONCLUSIONS Ths research ams at mprovng the performance of tabletng process wth these two qualty responses usng sx-sgma and grey relatonal analyss. Intally, the x and s charts are found n-control for both responses. But, the process was found capable for hardness but ncapable for weght. To mprove the performance of ths process, ths research ams at mprovng the performance of drect compresson process by adoptng DMAIC methodology. The man factors studed are machne speed (S), compresson force (F), and fllng depth (D) usng the L array. Then, the grey relatonal analyss based rankng s employed to dentfy the combnaton of optmal factor levels, whch s found as S F D. Intally, the Cˆ pk value for hardness s mproved from. to.. Whle, the Cˆ pk value for weght s enhance from 0.8 to Further, the MCpk ndex s mproved from 0.8 to.68. In concluson, DMAIC approach ncludng grey relatonal analyss s found effectve for mprovng the performance of drect compresson wth tablet s weght and hardness. REFERENCES [] Banker S., and Rhodes T., Modern Pharmaceutcs, (4th ed.) New York: Marcel Dekker, Inc., 00. [] L M.H., Al-Refae A., and Cheng.Y., DMAIC approach to mprove the capablty of SMT solders prntng process, IEEE Transactons on electroncs packagng Manufacturng, Vol., No., pp: 6-, 008. [] L M.H. and Al-Refae A., Improvng wooden parts qualty by adoptng DMAIC procedure, Qualty and Relablty Engneerng Internatonal, Vol. 4, pp: -60, 008. [4] Al-Refae, A., Optmzng SMT performance usng comparsons of Effcency between dfferent systems technque n DEA, IEEE Transactons on Electroncs Packagng Manufacturng, Vol., No. 4, pp: 6-64, 00. [] Al-Refae, A., Wu, T.H., and L, M.H.C., DEA approaches for solvng the mult-response problem n Taguch method, Artfcal Intellgence for Engneerng Desgn, Analyss and Manufacturng, Vol., pp: -, 00. [6] Al-Refae A. and L M.H., Optmzng the performance of plastc njecton moldng usng weghted addtve model n goal programmng, Internatonal Journal of Fuzzy System Applcatons, Vol., No. ), pp: 4-, 0. [] Deng L., Introducton to grey system theory. Journal of Grey Systems, Vol., No., pp:, 8. [8] Al-Refae, A., Optmzng correlated QCHs usng prncpal components analyss and DEA technques, Producton Plannng and Control, pp: -4, 00. [] Al-Refae A., L M.H., and T. K-C., Optmzng SUS 04 wre drawng process by grey relatonal analyss utlzng Taguch method, Journal of Unversty of Scence and Technology Bejng, Vol., pp: 4-, 008. [0] Montgomery C., Introducton to Statstcal Qualty Control, (6th ed.), USA: John Wley, 00. [] Plante D., Process capablty: a crteron for optmzng multple response product and process desgn, IIE Transactons,, 4-0, 00. [] Snka C., Motazedan F., and Cocks F., Ptt G., The effect of processng parameters on pharmaceutcal tablet propertes, Powder Technology, 8, pp: 6 84, 00. [] Mendez R., Muzzo F., and Velazquez C., Study of the effects of feed frames on powder blend propertes durng the fllng of tablet press des, Powder Technology, Vol. 00, pp:0 6, 00. [4] Belc A., Skrjanc I., Zupancc B., and Vrecer F. Tabletng process optmzaton wth the applcaton of fuzzy models, Internatonal Journal of Pharmaceutcs, Vol. 8, pp: 86-, 00. ISBN: ISSN: (Prnt); ISSN: (Onlne) IMECS 0

5 Proceedngs of the Internatonal MultConference of Engneers and Computer Scentsts 0 Vol II, IMECS 0, March -, 0, Hong Kong UC L=.4 Mean 0 48 X= LC L= UC L=4.844 StDev 4 S=.8 LC L=0.80 Fg. 4. The x -s charts for hardness mprovement. UC L=.6 Mean 4 X=4.04 LC L=.. UC L=.4 StDev.0..0 S=.4 0. LC L=0.84 Fg.. The x -s chart for weght mprovement. Table II EXPERIMENTAL RESULTS. number Hardness R R S/N Rato Average Weght R R S/N Rato Average ISBN: ISSN: (Prnt); ISSN: (Onlne) IMECS 0

6 Proceedngs of the Internatonal MultConference of Engneers and Computer Scentsts 0 Vol II, IMECS 0, March -, 0, Hong Kong TABLE III RESULTS OF GREY ANALYSIS Exp. Normalzed SNRs Absolute devatons Grey relatonal coeffcents () o () o (, ) o (, ) o Grey grade Ordnal value TOV TABLE IV OPTIMAL FACTOR LEVELS. Control factor Level Machne speed (S,0 Tab/hr) 0.60 (6) 0. () (0) Compresson Force (N) 0.8 (4) 0.0 () 0.6 (8) Fllng Depth (mm) 0.66 (40) 0.48 (0) 0.6 (6) The sum of ordnal values for each factor level n parenthess. ISBN: ISSN: (Prnt); ISSN: (Onlne) IMECS 0