Pharmaceutical Manufacturing Handbook: Production and

More documents

Recommendations

Info

282 SEMISOLID DOSAGES: OINTMENTS, CREAMS, AND GELS TABLE 5 USP Specifi cations for Some Offi cial Creams Cream Quality Control Tests Packaging and Storage Requirements Alclometasone Microbial limits, minimum Collapsible tubes or tight containers; store dipropionate fi ll, and assay at controlled room temperature Amphotericin B Minimum fi ll and assay Collapsible tubes or other well - closed containers Benzocaine Microbial limits, minimum Tight containers, protected from light, fi ll, and assay and avoid prolonged exposure to temperatures exceeding 30 ° C Betamethasone Minimum fi ll and assay Collapsible tubes or tight containers; store dipropionate at 25 ° C; excursions permitted between 15 and 30; protect from freezing Ciclopirox Minimum fi ll, pH, content Collapsible tubes at controlled room olamine of benzyl alcohol, and assay temperature Clobetasol Microbial limits, minimum Collapsible tubes or tight containers; store propionate fi ll, pH, and assay at controlled room temperature; do not refrigerate Clotrimazole Assay Collapsible tubes or tight containers at a temperature between 2 and 30 ° C Desoximetasone Minimum fi ll, pH, and Collapsible tubes at controlled room assay temperature Dibucaine Microbial limits, minimum Collapsible tubes or in tight, light - resistant fi ll, and assay containers Dienestrol Minimum fi ll and assay Collapsible tubes or in tight containers Difl orasone Microbial limits, minimum Collapsible tubes, preferably at controlled diacetate fi ll, and assay room temperature Fluocinolone Microbial limits, minimum Collapsible tubes or in tight containers acetonide fi ll, and assay Fluorouracil Microbial limits, minimum Tight containers and stored at controlled fi ll, and assay room temperature Gentamycin Minimum fi ll and assay Collapsible tubes or in other tight sulfate containers; avoid exposure to excessive heat Hydrocortisone Microbial limits, minimum Well - closed containers butyrate fi ll, pH, and assay Hydroquinone Minimum fi ll and assay Well - closed, light - resistant containers Lindane pH and assay Tight containers Meclocycline sulfosalicylate Minimum fi ll and assay Tight containers, protected from light Miconazole Minimum fi ll and assay Collapsible tubes or tight containers; store nitrate at controlled room temperature Monobenzone Assay Tight containers; avoid exposure to temperatures higher than 30 ° C Nystatin Minimum fi ll and assay Collapsible tubes or in other tight containers; avoid exposure to excessive heat Prednisolone Minimum fi ll and assay Collapsible tubes or in tight containers Tetracaine Microbial limits, minimum Collapsible, lined metal tubes hydrochloride fi ll, pH between 3.2 and 3.8, and assay Triamcinolone Microbial limits, minimum Tight containers acetonide fi ll, and assay
OINTMENTS AND CREAMS 283 Packaging and Storage The USP recommends packaging and storage requirements for each offi cial ointment and cream. Generally collapsible tubes, tight containers, or other well - closed containers are recommended for packing. They are stored in either a cool place or at controlled room temperatures. In some cases, special storage conditions are recommended: for example, protect from light, avoid exposure to excessive heat, avoid exposure to direct sunlight, avoid strong fl uorescent lighting, do not refrigerate, and avoid prolonged exposure to temperatures exceeding 30 ° C. Minimum Fill This test is performed to compare the weight or volume of product fi lled into each container with their labeled weight or volume. It helps in assessing the content uniformity of product. A minimum - fi ll test is applied only to those containers that contain not more than 150 g or mL of preparation. It is performed in two steps. Initially, labels from the product containers are removed. After washing and drying the surface, their weights are recorded ( W 1 ). In the second step, the entire product from each container is removed. After cleaning and drying, the weight of empty containers is recorded ( W 2 ). The difference between total weight ( W 1 ) and empty - container weight ( W 2 ) gives the weight of product. The USP recommends that the average net content of 10 containers should not be less than the labeled amount. If the product weight is less than 60 g or mL, the net content of any single container should not be less than 90% of the labeled amount. If the product weight is between 60 and 150 g or mL, the net content of any single container should not be less than 95% of the labeled amount. If these limits are not met, the test is repeated with an additional 20 containers. All semisolid topical preparations should meet these specifi cations [15] . Water Content The presence of minor quantities of water may alter the microbial, physical, and chemical stability of ointments and creams. Titrimetric methods (method I) are usually performed for determining the water content in these preparations. These methods are based on the quantitative reaction between water and anhydrous solution of sulfur and iodine in the presence of a buffer that can react with hydrogen ions. Special titration setups and reagents (Karl Fischer, KF) are used in these determinations. In the direct method (method Ia), about 35 mL of methanol is titrated with suffi cient quantity of KF reagent to the electrometric or visual endpoint (color change from canary yellow to amber). This blank titration helps to consume any moisture that may be present in the reaction medium. A known quantity of test material (ointment or cream) is added to the reaction medium, mixed, and again titrated with KF reagent to the reaction endpoint. The water content is determined by considering the volume of KF reagent consumed and its water equivalence factor. In the residual titration method (method Ib), a known excess quantity of KF reagent is added to the titration vessel, which is then back titrated with standardized water to the electrometric or visual endpoint. In the coulometric titration method (method Ic), the sample is dissolved in anhydrous methanol and injected into the reaction vessel that contains the anolyte, and the coulometric reaction is performed until the reaction endpoint. In some cases, methanol is replaced with other solvents. The maximum allowable limit of water in ointment preparations varies between 0.5 and 1.0%. The limit of water in bacitracin, chlortetracycline hydrochloride, and nystatin ointments is not more than 0.5%, whereas amphotericin
Page 1:
PHARMACEUTICAL MANUFACTURING HANDBO
Page 5 and 6:
PHARMACEUTICAL MANUFACTURING HANDBO
Page 7 and 8:
CONTRIBUTORS Susanna Abrahms é n -
Page 9 and 10:
CONTRIBUTORS vii Eddy Castellanos G
Page 11 and 12:
CONTENTS PREFACE xiii SECTION 1 MAN
Page 13:
CONTENTS xi 5.11 Transdermal Drug D
Page 17:
SECTION 1 MANUFACTURING SPECIALTIES
Page 20 and 21:
4 BIOTECHNOLOGY-DERIVED DRUG PRODUC
Page 22 and 23:
Page 24 and 25:
Page 26 and 27:
10 BIOTECHNOLOGY-DERIVED DRUG PRODU
Page 28 and 29:
Page 30 and 31:
Page 32 and 33:
Page 34 and 35:
Page 36 and 37:
Page 38 and 39:
Page 40 and 41:
Page 42 and 43:
Page 44 and 45:
Page 46 and 47:
Page 48 and 49:
Page 50 and 51:
34 REGULATORY CONSIDERATIONS IN APP
Page 52 and 53:
Page 54 and 55:
Page 56 and 57:
Page 58 and 59:
Page 60 and 61:
Page 62 and 63:
Page 64 and 65:
Page 66 and 67:
Page 68 and 69:
Page 70 and 71:
Page 72 and 73:
Page 75 and 76:
1.3 RADIOPHARMACEUTICAL MANUFACTURI
Page 77 and 78:
The terms tracer, radiotracer , and
Page 79 and 80:
number of atoms that disintegrate d
Page 81 and 82:
images that can also give quantitat
Page 83 and 84:
PRODUCT DEVELOPMENT 67 Product Stab
Page 85 and 86:
MANUFACTURING ASPECTS 69 stations s
Page 87 and 88:
In general, the manufacturing of mo
Page 89 and 90:
MANUFACTURING ASPECTS 73 Production
Page 91 and 92:
PRODUCT MANUFACTURING 75 tainer. Th
Page 93 and 94:
PRODUCT MANUFACTURING 77 practical
Page 95 and 96:
PRODUCT MANUFACTURING 79 these radi
Page 97 and 98:
PRODUCT MANUFACTURING 81 Most of th
Page 99 and 100:
PRODUCT MANUFACTURING 83 PET Radiop
Page 101 and 102:
PRODUCT MANUFACTURING 85 FIGURE 5 S
Page 103 and 104:
PRODUCT MANUFACTURING 87 tions in t
Page 105 and 106:
QUALITY CONSIDERATIONS 89 regulatio
Page 107 and 108:
L1 L2 TC-MDP + Hydr. Tc TC-MDP + Tc
Page 109 and 110:
EXTEMPORANEOUS PREPARATION OF RADIO
Page 111 and 112:
Independent of which regulation app
Page 113:
SECTION 2 ASEPTIC PROCESSING
Page 116 and 117:
100 STERILE PRODUCT MANUFACTURING 2
Page 118 and 119:
102 STERILE PRODUCT MANUFACTURING A
Page 120 and 121:
104 STERILE PRODUCT MANUFACTURING T
Page 122 and 123:
106 STERILE PRODUCT MANUFACTURING E
Page 124 and 125:
108 STERILE PRODUCT MANUFACTURING I
Page 126 and 127:
Page 128 and 129:
112 STERILE PRODUCT MANUFACTURING c
Page 130 and 131:
Page 132 and 133:
Page 134 and 135:
118 STERILE PRODUCT MANUFACTURING i
Page 136 and 137:
120 STERILE PRODUCT MANUFACTURING o
Page 138 and 139:
122 STERILE PRODUCT MANUFACTURING a
Page 140 and 141:
124 STERILE PRODUCT MANUFACTURING a
Page 142 and 143:
126 STERILE PRODUCT MANUFACTURING e
Page 144 and 145:
128 STERILE PRODUCT MANUFACTURING A
Page 146 and 147:
Page 148 and 149:
132 STERILE PRODUCT MANUFACTURING p
Page 150 and 151:
Page 153:
SECTION 3 FACILITY
Page 156 and 157:
140 EFFECT OF SCALE-UP ON OPERATION
Page 158 and 159:
Page 160 and 161:
Page 162 and 163:
Page 164 and 165:
Page 166 and 167:
Page 168 and 169:
Page 170 and 171:
Page 172 and 173:
Page 174 and 175:
Page 176 and 177:
160 PACKAGING AND LABELING 3.2.1 3.
Page 178 and 179:
162 PACKAGING AND LABELING signifi
Page 180 and 181:
164 PACKAGING AND LABELING Although
Page 182 and 183:
166 PACKAGING AND LABELING componen
Page 184 and 185:
168 PACKAGING AND LABELING sions. T
Page 186 and 187:
170 PACKAGING AND LABELING TABLE 1
Page 188 and 189:
172 PACKAGING AND LABELING the stab
Page 190 and 191:
174 PACKAGING AND LABELING and accu
Page 192 and 193:
176 PACKAGING AND LABELING The safe
Page 194 and 195:
178 PACKAGING AND LABELING If the p
Page 196 and 197:
180 PACKAGING AND LABELING exposure
Page 198 and 199:
182 PACKAGING AND LABELING In many
Page 200 and 201:
184 PACKAGING AND LABELING Nonpharm
Page 202 and 203:
186 PACKAGING AND LABELING In 1906,
Page 204 and 205:
188 PACKAGING AND LABELING A medica
Page 206 and 207:
190 PACKAGING AND LABELING The inst
Page 208 and 209:
192 PACKAGING AND LABELING the poun
Page 210 and 211:
194 PACKAGING AND LABELING • (4)
Page 212 and 213:
196 PACKAGING AND LABELING In the c
Page 214 and 215:
198 PACKAGING AND LABELING • Inte
Page 216 and 217:
200 PACKAGING AND LABELING 27. U.S.
Page 218 and 219:
202 CLEAN-FACILITY DESIGN, CONSTRUC
Page 220 and 221:
Page 222 and 223:
Page 224 and 225:
Page 226 and 227:
Page 228 and 229:
Page 230 and 231:
Page 232 and 233:
Page 234 and 235:
Page 236 and 237:
Page 238 and 239:
Page 240 and 241:
Page 242 and 243:
Page 244 and 245:
Page 246 and 247:
Page 248 and 249: 232 CLEAN-FACILITY DESIGN, CONSTRUC
Page 251 and 252: 4.1 SOLID DOSAGE FORMS Barbara R. C
Page 253 and 254: TABLE 2 Types of Solid Dosage Form
Page 255 and 256: (GI) tract or for systemic effects.
Page 257 and 258: EXCIPIENTS IN SOLID DOSE FORMULATIO
Page 259 and 260: EXCIPIENTS IN SOLID DOSE FORMULATIO
Page 261 and 262: HARD AND SOFT GELATIN CAPSULES 245
Page 267 and 268: participants from the FDA, industry
Page 269 and 270: in the mouth. Compressed lozenges (
Page 271 and 272: ittle fi lm, have no unpleasant tas
Page 273 and 274: CHEWING GUMS 257 4.1.10.2 Manufactu
Page 275 and 276: already dissolved in the saliva pri
Page 277 and 278: ORALLY DISINTEGRATING TABLETS 261 a
Page 279 and 280: tions. Some buccal formulations hav
Page 281: REFERENCES 265 32. Habib , W. , Kha
Page 284 and 285: 268 SEMISOLID DOSAGES: OINTMENTS, C
Page 330 and 331: 314 LIQUID DOSAGE FORMS 4.3.1 INTRO
Page 332 and 333: 316 LIQUID DOSAGE FORMS 4.3.2 GENER
Page 334 and 335: 318 LIQUID DOSAGE FORMS design, bui
Page 336 and 337: 320 LIQUID DOSAGE FORMS tions with
Page 338 and 339: 322 LIQUID DOSAGE FORMS Dosing Pump
Page 340 and 341: 324 LIQUID DOSAGE FORMS However, th
Page 342 and 343: 326 LIQUID DOSAGE FORMS Location of
Page 344 and 345: 328 LIQUID DOSAGE FORMS Solid drugs
Page 346 and 347: 330 LIQUID DOSAGE FORMS TABLE 3 Emu
Page 348 and 349:
332 LIQUID DOSAGE FORMS Temperature
Page 350 and 351:
334 LIQUID DOSAGE FORMS for viscosi
Page 352 and 353:
336 LIQUID DOSAGE FORMS spectrum, s
Page 354 and 355:
338 LIQUID DOSAGE FORMS Product Spe
Page 356 and 357:
340 LIQUID DOSAGE FORMS Liquid, Ext
Page 358 and 359:
342 LIQUID DOSAGE FORMS 7. Kourouna
Page 360 and 361:
344 LIQUID DOSAGE FORMS 46. Miller
Page 363 and 364:
5.1 CONTROLLED - RELEASE DOSAGE FOR
Page 365 and 366:
CONTROLLED-RELEASE DRUG DELIVERY SY
Page 367 and 368:
CONTROLLED-RELEASE FORMULATIONS 351
Page 369 and 370:
dosage forms [12] . For example, or
Page 371 and 372:
Degradation Liver Hydrolytic Enzyma
Page 373 and 374:
CONTROLLED-RELEASE ORAL DOSAGE FORM
Page 375 and 376:
DESIGN AND FABRICATION OF CONTROLLE
Page 377 and 378:
Page 379 and 380:
Page 381 and 382:
Page 383 and 384:
TECHNOLOGIES FOR DEVELOPING TRANSDE
Page 385 and 386:
TECHNOLOGIES FOR DEVELOPING TRANSDE
Page 387 and 388:
RELEASE OF DRUGS FROM CONTROLLED-RE
Page 389 and 390:
Page 391 and 392:
Page 393 and 394:
Page 395 and 396:
Page 397 and 398:
Page 399 and 400:
Page 401 and 402:
Page 403 and 404:
REFERENCES 387 16. Anal , A. K. ( 2
Page 405 and 406:
REFERENCES 389 57. M ü ller , R. H
Page 407 and 408:
REFERENCES 391 96. Sungthongjeen ,
Page 409 and 410:
5.2 PROGRESS IN DESIGN OF BIODEGRAD
Page 411 and 412:
INTRODUCTION 395 sequences. In addi
Page 413 and 414:
TABLE 2 Injectable Peptide/Proteins
Page 415 and 416:
PEPTIDE/PROTEIN-LOADED MICROSPHERE
Page 417 and 418:
Page 419 and 420:
Page 421 and 422:
ANALYTICAL CHARACTERIZATION 405 imm
Page 423 and 424:
IMMUNE SYSTEM INTERACTION WITH INJE
Page 425 and 426:
INJECTABLE PEPTIDE/PROTEIN-LOADED M
Page 427 and 428:
Page 429 and 430:
Page 431 and 432:
Page 433 and 434:
Page 435 and 436:
PEPTIDE/PROTEIN ENCAPSULATED INTO B
Page 437 and 438:
Page 439 and 440:
Page 441 and 442:
Page 443 and 444:
REFERENCES 427 novel ways to reduce
Page 445 and 446:
REFERENCES 429 31. Morlock , M. , K
Page 447 and 448:
REFERENCES 431 63. Lam , X. M. , Du
Page 449 and 450:
REFERENCES 433 95. van de Weert , M
Page 451 and 452:
REFERENCES 435 130. Bilati , U. , A
Page 453 and 454:
REFERENCES 437 166. Means , G. E. ,
Page 455 and 456:
REFERENCES 439 bic poly(lactide -co
Page 457:
REFERENCES 441 237. Singh , M. , Li
Page 460 and 461:
444 LIPOSOMES AND DRUG DELIVERY (sm
Page 462 and 463:
446 LIPOSOMES AND DRUG DELIVERY Con
Page 464 and 465:
448 LIPOSOMES AND DRUG DELIVERY and
Page 466 and 467:
450 LIPOSOMES AND DRUG DELIVERY tec
Page 468 and 469:
452 LIPOSOMES AND DRUG DELIVERY 250
Page 470 and 471:
454 LIPOSOMES AND DRUG DELIVERY a s
Page 472 and 473:
456 LIPOSOMES AND DRUG DELIVERY For
Page 474 and 475:
458 LIPOSOMES AND DRUG DELIVERY con
Page 476 and 477:
460 LIPOSOMES AND DRUG DELIVERY The
Page 478 and 479:
462 LIPOSOMES AND DRUG DELIVERY in
Page 480 and 481:
464 LIPOSOMES AND DRUG DELIVERY c a
Page 482 and 483:
466 LIPOSOMES AND DRUG DELIVERY Eve
Page 484 and 485:
468 LIPOSOMES AND DRUG DELIVERY inc
Page 486 and 487:
470 LIPOSOMES AND DRUG DELIVERY wit
Page 488 and 489:
472 LIPOSOMES AND DRUG DELIVERY i.v
Page 490 and 491:
474 LIPOSOMES AND DRUG DELIVERY for
Page 492 and 493:
476 LIPOSOMES AND DRUG DELIVERY bet
Page 494 and 495:
478 LIPOSOMES AND DRUG DELIVERY cli
Page 496 and 497:
480 LIPOSOMES AND DRUG DELIVERY lea
Page 498 and 499:
482 LIPOSOMES AND DRUG DELIVERY Vag
Page 500 and 501:
484 LIPOSOMES AND DRUG DELIVERY TAB
Page 502 and 503:
486 LIPOSOMES AND DRUG DELIVERY thr
Page 504 and 505:
488 LIPOSOMES AND DRUG DELIVERY TAB
Page 506 and 507:
490 LIPOSOMES AND DRUG DELIVERY tar
Page 508 and 509:
492 LIPOSOMES AND DRUG DELIVERY tha
Page 510 and 511:
494 LIPOSOMES AND DRUG DELIVERY wit
Page 512 and 513:
496 LIPOSOMES AND DRUG DELIVERY Pul
Page 514 and 515:
498 LIPOSOMES AND DRUG DELIVERY whi
Page 516 and 517:
500 LIPOSOMES AND DRUG DELIVERY Inc
Page 518 and 519:
502 LIPOSOMES AND DRUG DELIVERY Per
Page 520 and 521:
504 LIPOSOMES AND DRUG DELIVERY can
Page 522 and 523:
506 LIPOSOMES AND DRUG DELIVERY Tum
Page 524 and 525:
508 LIPOSOMES AND DRUG DELIVERY 25.
Page 526 and 527:
Page 528 and 529:
Page 530 and 531:
Page 532 and 533:
Page 534 and 535:
Page 536 and 537:
Page 538 and 539:
Page 540 and 541:
Page 542 and 543:
Page 544 and 545:
Page 546 and 547:
Page 548 and 549:
Page 551 and 552:
5.4 BIODEGRADABLE NANOPARTICLES Sud
Page 553 and 554:
NATURAL BIODEGRADABLE POLYMERIC NAN
Page 555 and 556:
Page 557 and 558:
Page 559 and 560:
and drug loading of gliadin nanopar
Page 561 and 562:
SYNTHETIC BIODEGRADABLE POLYMERIC N
Page 563 and 564:
APPLICATIONS OF BIODEGRADABLE NANOP
Page 565 and 566:
PHYSICOCHEMICAL CHARACTERIZATION OF
Page 567 and 568:
TARGETING NANOPARTICLES BY SURFACE
Page 569 and 570:
5.4.9 CONCLUSIONS Biodegradable nan
Page 571 and 572:
REFERENCES 555 of a model protein (
Page 573 and 574:
REFERENCES 557 65. Kaul , G. , and
Page 575 and 576:
REFERENCES 559 99. Carino , G. P. ,
Page 577 and 578:
REFERENCES 561 133. Na , K. , Lee ,
Page 579 and 580:
REFERENCES 563 168. Freitas , C. ,
Page 581 and 582:
5.5 RECOMBINANT SACCHAROMYCES CEREV
Page 583 and 584:
Potential Medical Applications of B
Page 585 and 586:
BIODRUG CONCEPT USING YEAST AS VECT
Page 587 and 588:
BIODRUG CONCEPT USING YEAST AS VECT
Page 589 and 590:
Cumulative ileal delivery of viable
Page 591 and 592:
tine [30] . No signal was detectabl
Page 593 and 594:
ORAL FORMULATION OF RECOMBINANT YEA
Page 595 and 596:
Cumulative ileal delivery of viable
Page 597 and 598:
ORAL FORMULATION OF RECOMBINANT YEA
Page 599 and 600:
Viable yeasts released (% of initia
Page 601 and 602:
Steidler et al. [47] have already d
Page 603 and 604:
REFERENCES 587 23. Steidler , L. (
Page 605 and 606:
REFERENCES 589 nant yeasts as novel
Page 607 and 608:
5.6 NASAL DELIVERY OF PEPTIDE AND N
Page 609 and 610:
fi rst - pass metabolism and gut -
Page 611 and 612:
[6] . The nasal blood vessels can b
Page 613 and 614:
FACTORS INFLUENCING NASAL DRUG ABSO
Page 615 and 616:
5.6.3.6 Type of Delivery Device FAC
Page 617 and 618:
FACTORS INFLUENCING NASAL DRUG ABSO
Page 619 and 620:
FIGURE 4 ( a ) Optinose multidose l
Page 621 and 622:
Dogs, sheep, and monkeys can be kep
Page 623 and 624:
NASAL DELIVERY OF PEPTIDE AND HIGH-
Page 625 and 626:
Page 627 and 628:
Page 629 and 630:
Page 631 and 632:
Page 633 and 634:
in solutions containing different c
Page 635 and 636:
Page 637 and 638:
Page 639 and 640:
Morphine plasma concentration (nmol
Page 641 and 642:
Concentration (μg/L) 1000 100 10 1
Page 643 and 644:
NASAL DELIVERY OF NONPEPTIDE MOLECU
Page 645 and 646:
NASAL DELIVERY OF NONPEPTIDE MOLECU
Page 647 and 648:
OPTION FOR DELIVERY OF DRUGS TO CEN
Page 649 and 650:
pseudostratifi ed epithelium compri
Page 651 and 652:
NASAL DELIVERY OF VACCINES 635 Howe
Page 653 and 654:
TABLE 5 Continued Delivery System/A
Page 655 and 656:
REFERENCES 639 23. Hardy , J. G. ,
Page 657 and 658:
REFERENCES 641 60. Collens , W. S.
Page 659 and 660:
REFERENCES 643 97. Eden , S. ( 1979
Page 661 and 662:
REFERENCES 645 comparison with oral
Page 663 and 664:
REFERENCES 647 172. Sakane , T. , A
Page 665 and 666:
REFERENCES 649 213. McCluskie , M.
Page 667 and 668:
5.7 NASAL POWDER DRUG DELIVERY Jele
Page 669 and 670:
NASAL DRY POWDER FORMULATIONS 653 t
Page 671 and 672:
POLYMERS IN NASAL POWDER DELIVERY S
Page 673 and 674:
POLYMERS IN NASAL POWDER DELIVERY S
Page 675 and 676:
MICROSPHERES AS NASAL DRUG DELIVERY
Page 677 and 678:
Page 679 and 680:
Page 681 and 682:
Page 683 and 684:
TOXICOLOGICAL CONSIDERATIONS 667 et
Page 685 and 686:
Summary of Research Work on Nasal D
Page 687 and 688:
Powder Formulation Preparation Meth
Page 689 and 690:
Powder Formulation Preparation Meth
Page 691 and 692:
REFERENCES 675 19. Van der Lubben ,
Page 693 and 694:
REFERENCES 677 54. Witschi , C. , a
Page 695 and 696:
REFERENCES 679 91. Varshosaz , J. ,
Page 697:
REFERENCES 681 126. Jorissen , M. ,
Page 700 and 701:
684 AEROSOL DRUG DELIVERY 5.8.8 5.8
Page 702 and 703:
686 AEROSOL DRUG DELIVERY other sig
Page 704 and 705:
688 AEROSOL DRUG DELIVERY are a num
Page 706 and 707:
690 AEROSOL DRUG DELIVERY 5.8.5 MET
Page 708 and 709:
692 AEROSOL DRUG DELIVERY TABLE 1 S
Page 710 and 711:
694 AEROSOL DRUG DELIVERY valve siz
Page 712 and 713:
696 AEROSOL DRUG DELIVERY Ferrule U
Page 714 and 715:
698 AEROSOL DRUG DELIVERY 5.8.5.6 A
Page 716 and 717:
700 AEROSOL DRUG DELIVERY 5.8.5.10
Page 718 and 719:
702 AEROSOL DRUG DELIVERY low inter
Page 720 and 721:
704 AEROSOL DRUG DELIVERY Transpare
Page 722 and 723:
706 AEROSOL DRUG DELIVERY of the cl
Page 724 and 725:
708 AEROSOL DRUG DELIVERY is achiev
Page 726 and 727:
710 AEROSOL DRUG DELIVERY Aerosol g
Page 728 and 729:
712 AEROSOL DRUG DELIVERY REFERENCE
Page 730 and 731:
714 AEROSOL DRUG DELIVERY 42. Witek
Page 732 and 733:
716 AEROSOL DRUG DELIVERY 81. Ohmor
Page 734 and 735:
718 AEROSOL DRUG DELIVERY 119. Lewi
Page 736 and 737:
720 AEROSOL DRUG DELIVERY 153. Terz
Page 738 and 739:
722 AEROSOL DRUG DELIVERY 189. Sham
Page 740 and 741:
724 AEROSOL DRUG DELIVERY 225. Newh
Page 742 and 743:
726 AEROSOL DRUG DELIVERY 263. Dolo
Page 745 and 746:
5.9 OCULAR DRUG DELIVERY Ilva D. Ru
Page 747 and 748:
CHALLENGES IN OCULAR DRUG DELIVERY
Page 749 and 750:
Page 751 and 752:
Page 753 and 754:
FORMULATION APPROACHES TO IMPROVE O
Page 755 and 756:
Page 757 and 758:
Drug Fluorescein FORMULATION APPROA
Page 759 and 760:
Page 761 and 762:
Page 763 and 764:
Page 765 and 766:
Page 767 and 768:
Page 769 and 770:
is characterized by a transient ove
Page 771 and 772:
REFERENCES 755 11. Klyce , S. D. ,
Page 773 and 774:
REFERENCES 757 53. Saettone , M. F.
Page 775 and 776:
REFERENCES 759 87. Lin , H. R. , an
Page 777 and 778:
REFERENCES 761 122. Durrani , A. M.
Page 779 and 780:
REFERENCES 763 158. Weyenberg , W.
Page 781 and 782:
REFERENCES 765 of various ophthalmi
Page 783:
REFERENCES 767 233. Grass , G. M. ,
Page 786 and 787:
770 MICROEMULSIONS AS DRUG DELIVERY
Page 788 and 789:
Page 790 and 791:
Page 792 and 793:
Page 794 and 795:
Page 796 and 797:
Page 798 and 799:
Page 800 and 801:
Page 802 and 803:
Page 804 and 805:
Page 806 and 807:
Page 808 and 809:
Page 810 and 811:
794 TRANSDERMAL DRUG DELIVERY 5.11.
Page 812 and 813:
796 TRANSDERMAL DRUG DELIVERY conta
Page 814 and 815:
798 TRANSDERMAL DRUG DELIVERY 5.11.
Page 816 and 817:
800 TRANSDERMAL DRUG DELIVERY FIGUR
Page 818 and 819:
802 TRANSDERMAL DRUG DELIVERY a rat
Page 820 and 821:
804 TRANSDERMAL DRUG DELIVERY passi
Page 822 and 823:
806 TRANSDERMAL DRUG DELIVERY 19. E
Page 825 and 826:
5.12 VAGINAL DRUG DELIVERY Jos é d
Page 827 and 828:
Therefore, this chapter discusses t
Page 829 and 830:
THE HUMAN VAGINA 813 thetic innerva
Page 831 and 832:
THE HUMAN VAGINA 815 the upper repr
Page 833 and 834:
THE HUMAN VAGINA 817 tant in the re
Page 835 and 836:
GENERAL FEATURES OF VAGINAL DRUG DE
Page 837 and 838:
Although this strategy may enhance
Page 839 and 840:
VAGINAL DRUG DELIVERY SYSTEMS 823 a
Page 841 and 842:
VAGINAL DRUG DELIVERY SYSTEMS 825 f
Page 843 and 844:
VAGINAL DRUG DELIVERY SYSTEMS 827 f
Page 845 and 846:
Amount released, μg/day 800 700 60
Page 847 and 848:
VAGINAL DRUG DELIVERY SYSTEMS 831 5
Page 849 and 850:
TABLE 4 Examples of Mucoadhesive Po
Page 851 and 852:
VAGINAL DRUG DELIVERY SYSTEMS 835 i
Page 853 and 854:
PHARMACEUTICAL EVALUATION OF VAGINA
Page 855 and 856:
Page 857 and 858:
Page 859 and 860:
CLINICAL USAGE AND POTENTIAL OF VAG
Page 861 and 862:
Page 863 and 864:
Page 865 and 866:
Page 867 and 868:
Page 869 and 870:
TABLE 6 Selected Drugs Administered
Page 871 and 872:
Selected Veterinary Vaginal Drug De
Page 873 and 874:
REFERENCES 857 Much work remains to
Page 875 and 876:
REFERENCES 859 33. Hocini , H. , Ba
Page 877 and 878:
REFERENCES 861 70. Kristmundsdottir
Page 879 and 880:
REFERENCES 863 105. McClelland , R.
Page 881 and 882:
REFERENCES 865 141. Kuyoh , M. A. ,
Page 883 and 884:
REFERENCES 867 178. Ondracek , J. ,
Page 885 and 886:
REFERENCES 869 212. Bagga , R. , Ra
Page 887 and 888:
REFERENCES 871 244. International W
Page 889 and 890:
REFERENCES 873 276. Mor , E. , Saad
Page 891 and 892:
REFERENCES 875 310. Saltzman , W. M
Page 893 and 894:
REFERENCES 877 vaginal microbicides
Page 895:
SECTION 6 TABLET PRODUCTION
Page 898 and 899:
882 PHARMACEUTICAL PREFORMULATION 6
Page 900 and 901:
884 PHARMACEUTICAL PREFORMULATION E
Page 902 and 903:
886 PHARMACEUTICAL PREFORMULATION T
Page 904 and 905:
Page 906 and 907:
Page 908 and 909:
892 PHARMACEUTICAL PREFORMULATION p
Page 910 and 911:
Page 912 and 913:
Page 914 and 915:
898 PHARMACEUTICAL PREFORMULATION l
Page 916 and 917:
Page 918 and 919:
902 PHARMACEUTICAL PREFORMULATION s
Page 920 and 921:
904 PHARMACEUTICAL PREFORMULATION C
Page 922 and 923:
906 PHARMACEUTICAL PREFORMULATION p
Page 924 and 925:
Page 926 and 927:
Page 928 and 929:
912 PHARMACEUTICAL PREFORMULATION D
Page 930 and 931:
Page 932 and 933:
916 PHARMACEUTICAL PREFORMULATION u
Page 934 and 935:
918 PHARMACEUTICAL PREFORMULATION d
Page 936 and 937:
920 PHARMACEUTICAL PREFORMULATION q
Page 938 and 939:
922 PHARMACEUTICAL PREFORMULATION w
Page 940 and 941:
Page 942 and 943:
Page 944 and 945:
928 PHARMACEUTICAL PREFORMULATION a
Page 946 and 947:
930 PHARMACEUTICAL PREFORMULATION a
Page 949 and 950:
6.2 ROLE OF PREFORMULATION IN DEVEL
Page 951 and 952:
maceutics ” documentation forms a
Page 953 and 954:
e altered without any change in the
Page 955 and 956:
Solubility Heat flow II I T m,II Ts
Page 957 and 958:
TABLE 2 Techniques to Characterize
Page 959 and 960:
Percent weight loss Heat flow (a) (
Page 961 and 962:
Heat flow Intensity 100 50 Endother
Page 963 and 964:
Change in mass (%) PHYSICAL/BULK CH
Page 965 and 966:
6.2.2.6 Powder Flow and Compressibi
Page 967 and 968:
Solvent required for 1 gm of solid
Page 969 and 970:
⎧ 100 ⎪ Ka 1+10 Percent ionized
Page 971 and 972:
Percent Ionization Percent Ionizati
Page 973 and 974:
SOLUBILITY CHARACTERISTICS 957 para
Page 975 and 976:
SOLUBILITY CHARACTERISTICS 959 of p
Page 977 and 978:
Dissolution studies pH solubility p
Page 979 and 980:
High Permeability Low SOLUBILITY CH
Page 981 and 982:
is evident form the fact [51] that
Page 983 and 984:
independent of initial drug concent
Page 985 and 986:
STABILITY CHARACTERISTICS 969 drug
Page 987 and 988:
6.2.5 CONCLUSIONS Preformulation te
Page 989 and 990:
REFERENCES 973 16. Huang , L. , and
Page 991:
54. 55. 56. REFERENCES 975 IFAMA (
Page 994 and 995:
978 TABLET DESIGN 6.3.9.3 Case Stud
Page 996 and 997:
980 TABLET DESIGN Another reason, t
Page 998 and 999:
982 TABLET DESIGN E: This ensures t
Page 1000 and 1001:
984 TABLET DESIGN substance would b
Page 1002 and 1003:
986 TABLET DESIGN Plasticity 1.0 0.
Page 1004 and 1005:
988 TABLET DESIGN Drug release (%)
Page 1006 and 1007:
990 TABLET DESIGN FIGURE 9 Dissolut
Page 1008 and 1009:
992 TABLET DESIGN TABLE 2 Number 1
Page 1010 and 1011:
994 TABLET DESIGN Formulation Table
Page 1012 and 1013:
996 TABLET DESIGN TABLE 4 Theophyll
Page 1014 and 1015:
998 TABLET DESIGN often very fi ne,
Page 1016 and 1017:
1000 TABLE 6 Formulations by Wet Gr
Page 1018 and 1019:
1002 TABLET DESIGN 6.3.6.2 FIGURE 1
Page 1020 and 1021:
1004 TABLET DESIGN TABLE 9 Papaveri
Page 1022 and 1023:
1006 TABLET DESIGN TABLE 12 Weight
Page 1024 and 1025:
1008 TABLET DESIGN (3.179 and 4.500
Page 1026 and 1027:
1010 TABLET DESIGN TABLE 14 Run Ord
Page 1028 and 1029:
1012 TABLET DESIGN Regression coeff
Page 1030 and 1031:
1014 TABLET DESIGN to being the out
Page 1032 and 1033:
1016 TABLET DESIGN Mechanical Prope
Page 1034 and 1035:
1018 TABLET DESIGN drawbacks (unsaf
Page 1036 and 1037:
1020 TABLET DESIGN TABLE 16 Basic F
Page 1038 and 1039:
1022 TABLET DESIGN PEG (e.g., Macro
Page 1040 and 1041:
1024 TABLET DESIGN 0.45% 0.40% 0.35
Page 1042 and 1043:
1026 TABLET DESIGN FIGURE 34 Granul
Page 1044 and 1045:
1028 TABLET DESIGN TABLE 19 SEPIFIL
Page 1046 and 1047:
1030 TABLET DESIGN (c) Blistering D
Page 1048 and 1049:
1032 TABLET DESIGN % Dextromethorph
Page 1050 and 1051:
1034 TABLET DESIGN (a) (b) 500 μm
Page 1052 and 1053:
1036 TABLET DESIGN threshold p c1 a
Page 1054 and 1055:
1038 TABLET DESIGN TABLE 24 Composi
Page 1056 and 1057:
1040 TABLET DESIGN Korsmeyer - Pepp
Page 1058 and 1059:
1042 TABLET DESIGN % Water uptake/d
Page 1060 and 1061:
1044 TABLET DESIGN FIGURE 47 Temper
Page 1062 and 1063:
1046 TABLET DESIGN REFERENCES 1. Un
Page 1064 and 1065:
1048 TABLET DESIGN 34. Congreve , M
Page 1066 and 1067:
1050 TABLET DESIGN 73. Miranda , A.
Page 1069 and 1070:
6.4 TABLET PRODUCTION SYSTEMS Katha
Page 1071 and 1072:
PHYSICS OF TABLET FORMATION 1055 en
Page 1073 and 1074:
Tablet production systems can be op
Page 1075 and 1076:
TABLETING MACHINES 1059 Eccentric T
Page 1077 and 1078:
TABLETING MACHINES 1061 In Figure 4
Page 1079 and 1080:
TABLETING MACHINE SIMULATORS (COMPA
Page 1081 and 1082:
TABLETING MACHINE SIMULATORS (COMPA
Page 1083 and 1084:
However, for mechanical compaction
Page 1085 and 1086:
INSTRUMENTATION OF TABLETING MACHIN
Page 1087 and 1088:
Force (kN) FIGURE 13 ANALYSIS OF TA
Page 1089 and 1090:
TABLE 4 Source Emschermann [91] (Fi
Page 1091 and 1092:
TABLE 6 Parameters Directly Deduced
Page 1093 and 1094:
TABLE 7 Parameters Calculated from
Page 1095 and 1096:
ANALYSIS OF TABLETING PROCESS 1079
Page 1097 and 1098:
TABLE 8 Source 3D model [143, 144,
Page 1099 and 1100:
6.4.11 SPECIAL ACCESSORIES OF TABLE
Page 1101 and 1102:
usually tends to vary. However, the
Page 1103 and 1104:
ing at punches and dies. Low produc
Page 1105 and 1106:
REFERENCES 1089 24. Elamin , A. , S
Page 1107 and 1108:
REFERENCES 1091 64. Yeh , C. , Alta
Page 1109 and 1110:
REFERENCES 1093 100. Armstrong , N.
Page 1111 and 1112:
REFERENCES 1095 140. Kuentz , M. ,
Page 1113 and 1114:
REFERENCES 1097 178. Hauschild , K.
Page 1115 and 1116:
6.5 CONTROLLED RELEASE OF DRUGS FRO
Page 1117 and 1118:
INTRODUCTION 1101 ings, and their e
Page 1119 and 1120:
needed to circulate them [57] . Typ
Page 1121 and 1122:
APPLICATIONS 1105 stream. During dr
Page 1123 and 1124:
APPLICATIONS 1107 TABLE 1 Theophyll
Page 1125 and 1126:
APPLICATIONS 1109 FIGURE 1 Release
Page 1127 and 1128:
(a) (b) APPLICATIONS 1111 FIGURE 3
Page 1129 and 1130:
APPLICATIONS 1113 FIGURE 5 Ternary
Page 1131 and 1132:
APPLICATIONS 1115 of the drug, dC/d
Page 1133 and 1134:
APPLICATIONS 1117 FIGURE 9 Ternary
Page 1135 and 1136:
Release rate (mg/min) 0.40 0.30 0.2
Page 1137 and 1138:
REFERENCES REFERENCES 1121 1. Lange
Page 1139 and 1140:
REFERENCES 1123 37. Lin , Y - K. ,
Page 1141 and 1142:
REFERENCES 1125 73. St - Onge , L.
Page 1143 and 1144:
REFERENCES 1127 107. Lai , J. - Y.
Page 1145 and 1146:
APPENDIX 1129 FIGURE A3 Release of
Page 1147 and 1148:
APPENDIX 1131 FIGURE A7 Release of
Page 1149 and 1150:
6.6 TABLET COMPRESSION Helton M. M.
Page 1151 and 1152:
during compression, which will also
Page 1153 and 1154:
of powder mixtures is usually chara
Page 1155 and 1156:
lose in combination with either tal
Page 1157 and 1158:
Due to the signifi cant nonlinearit
Page 1159 and 1160:
EQUIPMENT FOR TABLET COMPRESSION 11
Page 1161 and 1162:
Product Fill cam (mm) column height
Page 1163 and 1164:
TABLET PRESS TOOLING 1147 TABLE 1 T
Page 1165 and 1166:
TABLET PRESS TOOLING 1149 7. Tungst
Page 1167 and 1168:
FIGURE 6 Tooling standards confi gu
Page 1169 and 1170:
6.6.7 TABLE ENGRAVING Engraving is
Page 1171 and 1172:
Shallow and standard concave tablet
Page 1173 and 1174:
is the most popular bisect confi gu
Page 1175 and 1176:
PROBLEMS DURING TABLET MANUFACTURIN
Page 1177 and 1178:
thus reducing a potential variation
Page 1179:
REFERENCES 1163 27. Train , D. ( 19
Page 1182 and 1183:
1166 EFFECTS OF GRINDING IN PHARMAC
Page 1184 and 1185:
Page 1186 and 1187:
Page 1188 and 1189:
Page 1190 and 1191:
Page 1192 and 1193:
Page 1194 and 1195:
Page 1196 and 1197:
Page 1198 and 1199:
Page 1200 and 1201:
Page 1202 and 1203:
Page 1204 and 1205:
Page 1206 and 1207:
Page 1208 and 1209:
1192 ORAL EXTENDED-RELEASE FORMULAT
Page 1210 and 1211:
Page 1212 and 1213:
Page 1214 and 1215:
Page 1216 and 1217:
Page 1218 and 1219:
Page 1220 and 1221:
Page 1222 and 1223:
Page 1224 and 1225:
Page 1226 and 1227:
Page 1228 and 1229:
Page 1230 and 1231:
Page 1232 and 1233:
Page 1234 and 1235:
Page 1236 and 1237:
Page 1238 and 1239:
Page 1241 and 1242:
7.1 CYCLODEXTRIN - BASED NANOMATERI
Page 1243 and 1244:
OH (3) OH (2) HOCH 2 HOCH 2 O O OH
Page 1245 and 1246:
APPLICATIONS OF CYCLODEXTRINS IN NA
Page 1247 and 1248:
Percentage of release 100 90 80 70
Page 1249 and 1250:
Page 1251 and 1252:
Page 1253 and 1254:
Page 1255 and 1256:
O APPLICATIONS OF CYCLODEXTRINS IN
Page 1257 and 1258:
β - CDC6 loaded with the model dru
Page 1259 and 1260:
REFERENCES 1243 13. Stella , V. J.
Page 1261 and 1262:
REFERENCES 1245 49. Dodziuk , H. ,
Page 1263:
REFERENCES 1247 81. Memi şo ğlu -
Page 1266 and 1267:
1250 NANOTECHNOLOGY IN PHARMACEUTIC
Page 1268 and 1269:
Page 1270 and 1271:
Page 1272 and 1273:
Page 1274 and 1275:
Page 1276 and 1277:
Page 1278 and 1279:
Page 1280 and 1281:
Page 1282 and 1283:
Page 1284 and 1285:
Page 1286 and 1287:
Page 1288 and 1289:
Page 1290 and 1291:
Page 1292 and 1293:
Page 1294 and 1295:
Page 1296 and 1297:
Page 1298 and 1299:
Page 1300 and 1301:
Page 1302 and 1303:
Page 1304 and 1305:
Page 1306 and 1307:
1290 PHARMACEUTICAL NANOSYSTEMS 7.3
Page 1308 and 1309:
1292 PHARMACEUTICAL NANOSYSTEMS TAB
Page 1310 and 1311:
Page 1312 and 1313:
1296 PHARMACEUTICAL NANOSYSTEMS Lam
Page 1314 and 1315:
1298 PHARMACEUTICAL NANOSYSTEMS 7.3
Page 1316 and 1317:
1300 PHARMACEUTICAL NANOSYSTEMS sta
Page 1318 and 1319:
Page 1320 and 1321:
1304 PHARMACEUTICAL NANOSYSTEMS har
Page 1322 and 1323:
Page 1324 and 1325:
1308 PHARMACEUTICAL NANOSYSTEMS Sur
Page 1326 and 1327:
1310 PHARMACEUTICAL NANOSYSTEMS Aut
Page 1328 and 1329:
1312 PHARMACEUTICAL NANOSYSTEMS ®
Page 1330 and 1331:
1314 PHARMACEUTICAL NANOSYSTEMS 55.
Page 1332 and 1333:
1316 PHARMACEUTICAL NANOSYSTEMS 100
Page 1334 and 1335:
Page 1336 and 1337:
Page 1338 and 1339:
Page 1340 and 1341:
1324 PHARMACEUTICAL NANOSYSTEMS Nan
Page 1343 and 1344:
7.4 OIL - IN - WATER NANOSIZED EMUL
Page 1345 and 1346:
GENERATIONS OF OIL-IN-WATER NANOSIZ
Page 1347 and 1348:
Page 1349 and 1350:
Page 1351 and 1352:
Page 1353 and 1354:
Page 1355 and 1356:
Page 1357 and 1358:
DRUG-FREE/LOADED OIL-IN-WATER NANOS
Page 1359 and 1360:
EXCIPIENT INCLUSION: OIL-IN-WATER N
Page 1361 and 1362:
EXCIPIENT INCLUSION: OIL-IN-WATER N
Page 1363 and 1364:
MEDICAL APPLICATIONS OF OIL-IN-WATE
Page 1365 and 1366:
Page 1367 and 1368:
Page 1369 and 1370:
Page 1371 and 1372:
evaluation of the lipid hydroperoxi
Page 1373 and 1374:
REFERENCES 1357 21. Ott , G. , Sing
Page 1375 and 1376:
REFERENCES 1359 57. Harris , J. M.
Page 1377 and 1378:
REFERENCES 1361 94. Kim , Y. J. , K
Page 1379 and 1380:
REFERENCES 1363 131. Swietlikowska
Page 1381 and 1382:
REFERENCES 1365 167. Acheampong , A
Page 1383 and 1384:
INDEX Abortifacients, 850 Acyclovir
Page 1385 and 1386:
Lung cancer, 497-502 Lung toxicity,
show all

Pharmaceutical Manufacturing Handbook: Production and

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?