Pharmaceutical Manufacturing Handbook: Production and

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1226 CYCLODEXTRIN-BASED NANOMATERIALS IN PHARMACEUTICAL FIELD achieved by two approaches: (1) complexation of active ingredient with an appropriate CD and entrapment into polymeric nanoparticles to solve problems arising from the drug ’ s physicochemical properties or (2) modifi cation of CDs to render an amphiphilic character to these molecules, which allows CDs to self - align into nanoparticles in the form of nanospheres, nanocapsules, solid lipid nanoparticles, nanosize liposomes, and nanosize vesicles with or without the presence of surface - active agents. In light of current research, this chapter will deal with the following issues concerning the use of CDs and derivatives as nanomaterials for drug delivery: use of CDs (natural and synthetic) derivatives in the pharmaceutical fi eld and application of CDs in nanoparticulate drug delivery systems. A major part of the chapter will be focused on new CD derivatives, amphiphilic CDs, and the characterization, effi cacy, and safety of nanoparticles prepared from amphiphilic CDs. 7.1.1.1 Cyclodextrins in Pharmaceutical Field Natural Cyclodextrins Cyclodextrins are cyclic oligosaccharides obtained by the enzymatic degradation of starch. Major natural CDs are crystalline, homogeneous, nonhygroscopic substances which have a toruslike macroring shape built up from glucopyranose units, as seen in Figure 1 [1 – 3] . Cyclodextrins are named depending on the number of glucopyranose units. Major industrially produced CDs are named as follows; α - CD, possessing six units, β - CD, possessing seven units; and γ - CD, possessing eight units. Natural CDs have been demonstrated to have a special structure; that is, glucose residues in the CD ring possess the thermodynamically favored 4 C 1 chair conformation because all substituent groups are in equatorial position. Cyclodextrins behave like rigid compounds with two degrees of freedom: rotation at the glucosidic links C(4) – O(4) and C(1) – O(4) and rotations at the O(6) primary hydroxyl groups at the C(5) – C(6) band. As a consequence of this chair conformation, all secondary hydroxyl groups at C(2) and C(3) are located at the broader side of the CD torus in the equatorial position. Hydroxyl groups on C(2) point toward the cavity and hydroxyl groups on C(3) point outward. The primary hydroxyl groups at the C6 position are located at the narrower side of the torus. These hydroxyl groups ensure good water solubility for the natural CDs. The cavity of the torus is lined with a ring of C − H groups (C3), a ring of glucosidic oxygen atoms, and another ring of C − H groups (C5). Thus, the cavity of CDs exhibits an apolar character. This is accompanied by a high electron density and Lewis base property. The physicochemical characteristics and inclusion behavior of CDs are a direct consequence of these special binding conditions [4, 5] . Certain physicochemical characteristics of natural CDs are given in Table 1 . Cyclodextrin Derivatives Natural CDs were reported to form total or partial inclusion complexes with several drugs to improve the aqueous solubility and stability under physiological or ambient conditions, reduce or mask completely the side effects associated with the included drug, and increase compatibility of the drug with other drugs in the formulation or excipients while improving patient compliance by masking the taste or odor of the active ingredient [6 – 8] .
OH (3) OH (2) HOCH 2 HOCH 2 O O OH O OH O Primary face Apolar cavity Secondary face O O OH OH OH OH HO OH (6 ) CH2OH O O HO CH2OH CH2OH O CH 2OH CH 2OH FIGURE 1 Schematic representation of natural CD structure and modifi cation sites. HO HO 3 O HO 2 HO OH O Modification sites TABLE 1 Some Physicochemical Characteristics of Natural Cyclodextrins Characteristics α - CD β - CD Number of glucose units 6 7 Molecular weight, g/mol 972 1135 Internal diameter, Å 4.7 – 5.2 6.0 – 6.4 External diameter, Å 14.2 – 15.0 15.0 – 15.8 Depth, Å 7.9 – 8.0 7.9 – 8.0 Solubility in water (25 ° C), g/L 145 18.5 Crystal water, w % 10.2 13.2 – 14.5 Approximative cavity volume in 1 mol CD, Å 3 174 262 Melting point, ° C 250 – 260 255 – 265 Half - life in 1 M HCl at 60 ° C, h 6.2 5.4 Crystal forms (from water) Hexagonal Monoclinic plate parallelogram Partial molar volumes in solution, mL/mol 611.4 703.8 HO O O O INTRODUCTION 1227 6 γ - CD 8 1297 7.5 – 8.3 17.1 – 17.9 7.9 – 8.0 232 8.13 – 17.7 472 240 – 245 3.0 Quadratic prism 801.2
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PHARMACEUTICAL MANUFACTURING HANDBO
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PHARMACEUTICAL MANUFACTURING HANDBO
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CONTRIBUTORS Susanna Abrahms é n -
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CONTRIBUTORS vii Eddy Castellanos G
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CONTENTS PREFACE xiii SECTION 1 MAN
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CONTENTS xi 5.11 Transdermal Drug D
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SECTION 1 MANUFACTURING SPECIALTIES
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4 BIOTECHNOLOGY-DERIVED DRUG PRODUC
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10 BIOTECHNOLOGY-DERIVED DRUG PRODU
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34 REGULATORY CONSIDERATIONS IN APP
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1.3 RADIOPHARMACEUTICAL MANUFACTURI
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The terms tracer, radiotracer , and
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number of atoms that disintegrate d
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images that can also give quantitat
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PRODUCT DEVELOPMENT 67 Product Stab
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MANUFACTURING ASPECTS 69 stations s
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In general, the manufacturing of mo
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MANUFACTURING ASPECTS 73 Production
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PRODUCT MANUFACTURING 75 tainer. Th
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PRODUCT MANUFACTURING 77 practical
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PRODUCT MANUFACTURING 79 these radi
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PRODUCT MANUFACTURING 81 Most of th
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PRODUCT MANUFACTURING 83 PET Radiop
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PRODUCT MANUFACTURING 85 FIGURE 5 S
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PRODUCT MANUFACTURING 87 tions in t
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QUALITY CONSIDERATIONS 89 regulatio
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L1 L2 TC-MDP + Hydr. Tc TC-MDP + Tc
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EXTEMPORANEOUS PREPARATION OF RADIO
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Independent of which regulation app
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SECTION 2 ASEPTIC PROCESSING
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100 STERILE PRODUCT MANUFACTURING 2
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102 STERILE PRODUCT MANUFACTURING A
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104 STERILE PRODUCT MANUFACTURING T
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106 STERILE PRODUCT MANUFACTURING E
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108 STERILE PRODUCT MANUFACTURING I
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112 STERILE PRODUCT MANUFACTURING c
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118 STERILE PRODUCT MANUFACTURING i
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120 STERILE PRODUCT MANUFACTURING o
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122 STERILE PRODUCT MANUFACTURING a
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124 STERILE PRODUCT MANUFACTURING a
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126 STERILE PRODUCT MANUFACTURING e
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128 STERILE PRODUCT MANUFACTURING A
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132 STERILE PRODUCT MANUFACTURING p
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SECTION 3 FACILITY
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140 EFFECT OF SCALE-UP ON OPERATION
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160 PACKAGING AND LABELING 3.2.1 3.
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162 PACKAGING AND LABELING signifi
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164 PACKAGING AND LABELING Although
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166 PACKAGING AND LABELING componen
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168 PACKAGING AND LABELING sions. T
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170 PACKAGING AND LABELING TABLE 1
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172 PACKAGING AND LABELING the stab
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174 PACKAGING AND LABELING and accu
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176 PACKAGING AND LABELING The safe
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178 PACKAGING AND LABELING If the p
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180 PACKAGING AND LABELING exposure
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182 PACKAGING AND LABELING In many
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184 PACKAGING AND LABELING Nonpharm
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186 PACKAGING AND LABELING In 1906,
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188 PACKAGING AND LABELING A medica
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190 PACKAGING AND LABELING The inst
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192 PACKAGING AND LABELING the poun
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194 PACKAGING AND LABELING • (4)
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196 PACKAGING AND LABELING In the c
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198 PACKAGING AND LABELING • Inte
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200 PACKAGING AND LABELING 27. U.S.
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202 CLEAN-FACILITY DESIGN, CONSTRUC
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4.1 SOLID DOSAGE FORMS Barbara R. C
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TABLE 2 Types of Solid Dosage Form
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(GI) tract or for systemic effects.
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EXCIPIENTS IN SOLID DOSE FORMULATIO
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EXCIPIENTS IN SOLID DOSE FORMULATIO
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HARD AND SOFT GELATIN CAPSULES 245
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participants from the FDA, industry
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in the mouth. Compressed lozenges (
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ittle fi lm, have no unpleasant tas
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CHEWING GUMS 257 4.1.10.2 Manufactu
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already dissolved in the saliva pri
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ORALLY DISINTEGRATING TABLETS 261 a
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tions. Some buccal formulations hav
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REFERENCES 265 32. Habib , W. , Kha
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268 SEMISOLID DOSAGES: OINTMENTS, C
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314 LIQUID DOSAGE FORMS 4.3.1 INTRO
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316 LIQUID DOSAGE FORMS 4.3.2 GENER
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318 LIQUID DOSAGE FORMS design, bui
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320 LIQUID DOSAGE FORMS tions with
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322 LIQUID DOSAGE FORMS Dosing Pump
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324 LIQUID DOSAGE FORMS However, th
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326 LIQUID DOSAGE FORMS Location of
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328 LIQUID DOSAGE FORMS Solid drugs
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330 LIQUID DOSAGE FORMS TABLE 3 Emu
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332 LIQUID DOSAGE FORMS Temperature
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334 LIQUID DOSAGE FORMS for viscosi
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336 LIQUID DOSAGE FORMS spectrum, s
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338 LIQUID DOSAGE FORMS Product Spe
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340 LIQUID DOSAGE FORMS Liquid, Ext
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342 LIQUID DOSAGE FORMS 7. Kourouna
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344 LIQUID DOSAGE FORMS 46. Miller
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5.1 CONTROLLED - RELEASE DOSAGE FOR
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CONTROLLED-RELEASE DRUG DELIVERY SY
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CONTROLLED-RELEASE FORMULATIONS 351
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dosage forms [12] . For example, or
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Degradation Liver Hydrolytic Enzyma
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CONTROLLED-RELEASE ORAL DOSAGE FORM
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DESIGN AND FABRICATION OF CONTROLLE
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TECHNOLOGIES FOR DEVELOPING TRANSDE
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TECHNOLOGIES FOR DEVELOPING TRANSDE
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RELEASE OF DRUGS FROM CONTROLLED-RE
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REFERENCES 387 16. Anal , A. K. ( 2
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REFERENCES 389 57. M ü ller , R. H
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REFERENCES 391 96. Sungthongjeen ,
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5.2 PROGRESS IN DESIGN OF BIODEGRAD
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INTRODUCTION 395 sequences. In addi
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TABLE 2 Injectable Peptide/Proteins
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PEPTIDE/PROTEIN-LOADED MICROSPHERE
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ANALYTICAL CHARACTERIZATION 405 imm
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IMMUNE SYSTEM INTERACTION WITH INJE
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INJECTABLE PEPTIDE/PROTEIN-LOADED M
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PEPTIDE/PROTEIN ENCAPSULATED INTO B
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REFERENCES 427 novel ways to reduce
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REFERENCES 429 31. Morlock , M. , K
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REFERENCES 431 63. Lam , X. M. , Du
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REFERENCES 433 95. van de Weert , M
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REFERENCES 435 130. Bilati , U. , A
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REFERENCES 437 166. Means , G. E. ,
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REFERENCES 439 bic poly(lactide -co
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REFERENCES 441 237. Singh , M. , Li
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444 LIPOSOMES AND DRUG DELIVERY (sm
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446 LIPOSOMES AND DRUG DELIVERY Con
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448 LIPOSOMES AND DRUG DELIVERY and
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450 LIPOSOMES AND DRUG DELIVERY tec
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452 LIPOSOMES AND DRUG DELIVERY 250
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454 LIPOSOMES AND DRUG DELIVERY a s
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456 LIPOSOMES AND DRUG DELIVERY For
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458 LIPOSOMES AND DRUG DELIVERY con
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460 LIPOSOMES AND DRUG DELIVERY The
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462 LIPOSOMES AND DRUG DELIVERY in
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464 LIPOSOMES AND DRUG DELIVERY c a
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466 LIPOSOMES AND DRUG DELIVERY Eve
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468 LIPOSOMES AND DRUG DELIVERY inc
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470 LIPOSOMES AND DRUG DELIVERY wit
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472 LIPOSOMES AND DRUG DELIVERY i.v
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474 LIPOSOMES AND DRUG DELIVERY for
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476 LIPOSOMES AND DRUG DELIVERY bet
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478 LIPOSOMES AND DRUG DELIVERY cli
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480 LIPOSOMES AND DRUG DELIVERY lea
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482 LIPOSOMES AND DRUG DELIVERY Vag
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484 LIPOSOMES AND DRUG DELIVERY TAB
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486 LIPOSOMES AND DRUG DELIVERY thr
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488 LIPOSOMES AND DRUG DELIVERY TAB
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490 LIPOSOMES AND DRUG DELIVERY tar
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492 LIPOSOMES AND DRUG DELIVERY tha
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494 LIPOSOMES AND DRUG DELIVERY wit
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496 LIPOSOMES AND DRUG DELIVERY Pul
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498 LIPOSOMES AND DRUG DELIVERY whi
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500 LIPOSOMES AND DRUG DELIVERY Inc
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502 LIPOSOMES AND DRUG DELIVERY Per
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504 LIPOSOMES AND DRUG DELIVERY can
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506 LIPOSOMES AND DRUG DELIVERY Tum
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508 LIPOSOMES AND DRUG DELIVERY 25.
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5.4 BIODEGRADABLE NANOPARTICLES Sud
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NATURAL BIODEGRADABLE POLYMERIC NAN
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and drug loading of gliadin nanopar
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SYNTHETIC BIODEGRADABLE POLYMERIC N
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APPLICATIONS OF BIODEGRADABLE NANOP
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PHYSICOCHEMICAL CHARACTERIZATION OF
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TARGETING NANOPARTICLES BY SURFACE
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5.4.9 CONCLUSIONS Biodegradable nan
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REFERENCES 555 of a model protein (
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REFERENCES 557 65. Kaul , G. , and
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REFERENCES 559 99. Carino , G. P. ,
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REFERENCES 561 133. Na , K. , Lee ,
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REFERENCES 563 168. Freitas , C. ,
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5.5 RECOMBINANT SACCHAROMYCES CEREV
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Potential Medical Applications of B
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BIODRUG CONCEPT USING YEAST AS VECT
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BIODRUG CONCEPT USING YEAST AS VECT
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Cumulative ileal delivery of viable
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tine [30] . No signal was detectabl
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ORAL FORMULATION OF RECOMBINANT YEA
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Cumulative ileal delivery of viable
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ORAL FORMULATION OF RECOMBINANT YEA
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Viable yeasts released (% of initia
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Steidler et al. [47] have already d
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REFERENCES 587 23. Steidler , L. (
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REFERENCES 589 nant yeasts as novel
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5.6 NASAL DELIVERY OF PEPTIDE AND N
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fi rst - pass metabolism and gut -
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[6] . The nasal blood vessels can b
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FACTORS INFLUENCING NASAL DRUG ABSO
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5.6.3.6 Type of Delivery Device FAC
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FACTORS INFLUENCING NASAL DRUG ABSO
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FIGURE 4 ( a ) Optinose multidose l
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Dogs, sheep, and monkeys can be kep
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NASAL DELIVERY OF PEPTIDE AND HIGH-
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in solutions containing different c
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Morphine plasma concentration (nmol
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Concentration (μg/L) 1000 100 10 1
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NASAL DELIVERY OF NONPEPTIDE MOLECU
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NASAL DELIVERY OF NONPEPTIDE MOLECU
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OPTION FOR DELIVERY OF DRUGS TO CEN
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pseudostratifi ed epithelium compri
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NASAL DELIVERY OF VACCINES 635 Howe
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TABLE 5 Continued Delivery System/A
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REFERENCES 639 23. Hardy , J. G. ,
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REFERENCES 641 60. Collens , W. S.
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REFERENCES 643 97. Eden , S. ( 1979
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REFERENCES 645 comparison with oral
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REFERENCES 647 172. Sakane , T. , A
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REFERENCES 649 213. McCluskie , M.
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5.7 NASAL POWDER DRUG DELIVERY Jele
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NASAL DRY POWDER FORMULATIONS 653 t
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POLYMERS IN NASAL POWDER DELIVERY S
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POLYMERS IN NASAL POWDER DELIVERY S
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MICROSPHERES AS NASAL DRUG DELIVERY
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TOXICOLOGICAL CONSIDERATIONS 667 et
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Summary of Research Work on Nasal D
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Powder Formulation Preparation Meth
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Powder Formulation Preparation Meth
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REFERENCES 675 19. Van der Lubben ,
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REFERENCES 677 54. Witschi , C. , a
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REFERENCES 679 91. Varshosaz , J. ,
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REFERENCES 681 126. Jorissen , M. ,
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684 AEROSOL DRUG DELIVERY 5.8.8 5.8
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686 AEROSOL DRUG DELIVERY other sig
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688 AEROSOL DRUG DELIVERY are a num
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690 AEROSOL DRUG DELIVERY 5.8.5 MET
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692 AEROSOL DRUG DELIVERY TABLE 1 S
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694 AEROSOL DRUG DELIVERY valve siz
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696 AEROSOL DRUG DELIVERY Ferrule U
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698 AEROSOL DRUG DELIVERY 5.8.5.6 A
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700 AEROSOL DRUG DELIVERY 5.8.5.10
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702 AEROSOL DRUG DELIVERY low inter
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704 AEROSOL DRUG DELIVERY Transpare
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706 AEROSOL DRUG DELIVERY of the cl
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708 AEROSOL DRUG DELIVERY is achiev
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710 AEROSOL DRUG DELIVERY Aerosol g
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712 AEROSOL DRUG DELIVERY REFERENCE
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714 AEROSOL DRUG DELIVERY 42. Witek
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716 AEROSOL DRUG DELIVERY 81. Ohmor
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718 AEROSOL DRUG DELIVERY 119. Lewi
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720 AEROSOL DRUG DELIVERY 153. Terz
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722 AEROSOL DRUG DELIVERY 189. Sham
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724 AEROSOL DRUG DELIVERY 225. Newh
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726 AEROSOL DRUG DELIVERY 263. Dolo
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5.9 OCULAR DRUG DELIVERY Ilva D. Ru
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CHALLENGES IN OCULAR DRUG DELIVERY
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FORMULATION APPROACHES TO IMPROVE O
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Drug Fluorescein FORMULATION APPROA
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is characterized by a transient ove
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REFERENCES 755 11. Klyce , S. D. ,
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REFERENCES 757 53. Saettone , M. F.
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REFERENCES 759 87. Lin , H. R. , an
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REFERENCES 761 122. Durrani , A. M.
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REFERENCES 763 158. Weyenberg , W.
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REFERENCES 765 of various ophthalmi
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REFERENCES 767 233. Grass , G. M. ,
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770 MICROEMULSIONS AS DRUG DELIVERY
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794 TRANSDERMAL DRUG DELIVERY 5.11.
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796 TRANSDERMAL DRUG DELIVERY conta
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798 TRANSDERMAL DRUG DELIVERY 5.11.
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800 TRANSDERMAL DRUG DELIVERY FIGUR
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802 TRANSDERMAL DRUG DELIVERY a rat
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804 TRANSDERMAL DRUG DELIVERY passi
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806 TRANSDERMAL DRUG DELIVERY 19. E
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5.12 VAGINAL DRUG DELIVERY Jos é d
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Therefore, this chapter discusses t
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THE HUMAN VAGINA 813 thetic innerva
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THE HUMAN VAGINA 815 the upper repr
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THE HUMAN VAGINA 817 tant in the re
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GENERAL FEATURES OF VAGINAL DRUG DE
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Although this strategy may enhance
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VAGINAL DRUG DELIVERY SYSTEMS 823 a
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VAGINAL DRUG DELIVERY SYSTEMS 825 f
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VAGINAL DRUG DELIVERY SYSTEMS 827 f
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Amount released, μg/day 800 700 60
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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: 1176 EFFECTS OF GRINDING IN PHARMAC
Page 1208 and 1209: 1192 ORAL EXTENDED-RELEASE FORMULAT
Page 1241: 7.1 CYCLODEXTRIN - BASED NANOMATERI
Page 1245 and 1246: APPLICATIONS OF CYCLODEXTRINS IN NA
Page 1247 and 1248: Percentage of release 100 90 80 70
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 1292 and 1293:
1276 NANOTECHNOLOGY IN PHARMACEUTIC
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,
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