Pharmaceutical Manufacturing Handbook: Production and

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632 NASAL DELIVERY OF PEPTIDE AND NONPEPTIDE DRUGS TABLE 4 Nose - to - Brain Delivery of Agents in Different Species Drug/Molecule Path Followed Humans Arginine - vasopressin — a Adrenocorticotrophin — a Cholecystokinin — a Diazepam — a Insulin — a technetium - 99m - diethylenetriaminepentacetic acid Direct from nose to brain Apomorphine Nasal cavity → CSF Melatonin/hydroxycobalamin Nasal cavity → CSF Melanocortin, vasopressin, and insulin Nasal cavity → CSF Rats Zidovudine Nasal cavity → CSF, nasal cavity → systemic circulation Dextromethorphan HCl Direct from nose to brain Cephalexin Nasal cavity → CSF, nasal cavity → systemic circulation Sulfonamides Nasal cavity → CSF, nasal cavity → systemic circulation Dextran Nasal cavity → olfactory mucosa → CNS and also nasal cavity → systemic circulation Dopamine Direct from nose to brain Cocaine Direct from nose to brain Dihydroergotamine Direct from nose to brain Insulin Direct from nose to brain Dopamine Nasal cavity → CSF Methotrexate Nasal cavity → CSF Nerve growth factor Direct from nose to brain via olfactory pathway WGA – HRP (wheat germ Direct from nose to brain via olfactory nerve agglutinin – horseradish peroxidase) and bulb Zolmitriptan Direct from nose to brain Leptin Direct from nose to brain Morphine Direct nose to brain via olfactory pathway Nimodipine Direct nose to brain via olfactory bulb and nasal cavity → CSF Meptazinol hydrochloride Nasal cavity → CSF Estradiol Nasal cavity → CSF via olfactory neurons a Facilitated transport to brain based on functional evidence in humans. Reference 158 159 160 161 158 , 162 163 164 165 166 167 168 169 170 , 171 neuronal components comprising the odorant detectors. The olfactory region is mainly located on the nasal septum and partly on the superior and middle turbinates. It occupies only a small region in humans of about 10 cm 2 in the roof of the nasal cavity, as compared to around 150 cm 2 in dogs. The olfactory epithelium is a 172 173 141 174 175 173 176 177 178 179 180 181 182 183 184
pseudostratifi ed epithelium comprising three types of cells: olfactory receptor cells, supporting cells, and basal cells. The receptor cells are elongated bipolar neurons located in the middle stratum of the epithelium, interspersed among the sustentacular cells; the microvilli cover the supporting cells, which extend from the mucosal surface to the basal membrane; while the basal cells are located in the basal surface of the neuroepithelium. These basal cells go on to differentiate, becoming new receptor cells [140, 185, 186] . The surface of the nasal cavity measures about 180 cm 2 in humans as compared to about 10 cm 2 in rats, and the olfactory region is reported to constitute about 3% of the nasal cavity in humans and 50% in rats. Some other differences include the fact that in adult humans the volume of CSF is about 160 mL while it is only about 150 μ L in rats; also, the CSF is replaced about three times daily in humans, whereas in rats it is replaced hourly. Hence, though there is suffi cient evidence regarding nose - to - brain delivery, especially in rats and in some cases in humans, the impact of these factors on the interpretation of the results between the two species could be signifi cant [155, 187] . 5.6.9 NASAL DELIVERY OF VACCINES NASAL DELIVERY OF VACCINES 633 The discovery of vaccines for smallpox, cholera, and typhoid and the variety of vaccines now available have led to a signifi cant reduction in the mortality and morbidity due to many diseases, with smallpox being the fi rst to have been completely eradicated and poliomyelitis targeted to be the next. At present, the World Health Organization is working toward the complete elimination of poliomyelitis throughout the world [188, 189] . However, since Jenner discovered the vaccine for smallpox more than two centuries ago [190] , only some 50 vaccines have been approved for use, and few additional vaccines have been discovered. Most of those in current use are administered parenterally; they can induce only a systemic immune response, not mucosal immunity. Obviously the latter is very important in the prevention and treatment of infectious diseases, be they due to viral, bacterial, or parasitic pathogens that attack via the mucosal surfaces [190] . The criteria to be met in designing a vaccine formulation include the following: The vaccine should have the capacity to produce lifelong immunity, be able to act against the different strains and variants or the subtypes of the organisms, be effective in all age groups, be able to act quickly and also to induce immunity in the fetus when the mother is treated, be able to act effectively after a single treatment, and ideally be administered noninvasively. Finally, such a vaccine must be relatively inexpensive and remain active under a variety of conditions, especially not requiring the cold chain [191] . The following section addresses the need for needle - free vaccines with formulations based on safer adjuvant and delivery systems. 5.6.9.1 Nasal Vaccines: Ideal Noninvasive Route When we talk about targeting the pathogens entering through the mucosal surfaces, the route that usually comes to mind is the oral route. However, this route has its drawbacks for several reasons, such as the fact that the antigen used is degraded along with the gastric contents; furthermore, there is also the diffi culty of reaching the antigen - presenting cells [192] . In comparison to the oral route, nasal vaccination
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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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Page 605 and 606: REFERENCES 589 nant yeasts as novel
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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
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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 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
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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. ,
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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
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TABLE 4 Examples of Mucoadhesive Po
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VAGINAL DRUG DELIVERY SYSTEMS 835 i
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PHARMACEUTICAL EVALUATION OF VAGINA
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CLINICAL USAGE AND POTENTIAL OF VAG
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TABLE 6 Selected Drugs Administered
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Selected Veterinary Vaginal Drug De
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REFERENCES 857 Much work remains to
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REFERENCES 859 33. Hocini , H. , Ba
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REFERENCES 861 70. Kristmundsdottir
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REFERENCES 863 105. McClelland , R.
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REFERENCES 865 141. Kuyoh , M. A. ,
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REFERENCES 867 178. Ondracek , J. ,
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REFERENCES 869 212. Bagga , R. , Ra
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REFERENCES 871 244. International W
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REFERENCES 873 276. Mor , E. , Saad
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REFERENCES 875 310. Saltzman , W. M
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REFERENCES 877 vaginal microbicides
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SECTION 6 TABLET PRODUCTION
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882 PHARMACEUTICAL PREFORMULATION 6
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884 PHARMACEUTICAL PREFORMULATION E
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886 PHARMACEUTICAL PREFORMULATION T
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892 PHARMACEUTICAL PREFORMULATION p
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898 PHARMACEUTICAL PREFORMULATION l
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902 PHARMACEUTICAL PREFORMULATION s
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904 PHARMACEUTICAL PREFORMULATION C
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906 PHARMACEUTICAL PREFORMULATION p
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912 PHARMACEUTICAL PREFORMULATION D
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916 PHARMACEUTICAL PREFORMULATION u
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918 PHARMACEUTICAL PREFORMULATION d
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920 PHARMACEUTICAL PREFORMULATION q
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922 PHARMACEUTICAL PREFORMULATION w
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928 PHARMACEUTICAL PREFORMULATION a
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930 PHARMACEUTICAL PREFORMULATION a
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6.2 ROLE OF PREFORMULATION IN DEVEL
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maceutics ” documentation forms a
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e altered without any change in the
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Solubility Heat flow II I T m,II Ts
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TABLE 2 Techniques to Characterize
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Percent weight loss Heat flow (a) (
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Heat flow Intensity 100 50 Endother
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Change in mass (%) PHYSICAL/BULK CH
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6.2.2.6 Powder Flow and Compressibi
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Solvent required for 1 gm of solid
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⎧ 100 ⎪ Ka 1+10 Percent ionized
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Percent Ionization Percent Ionizati
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SOLUBILITY CHARACTERISTICS 957 para
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SOLUBILITY CHARACTERISTICS 959 of p
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Dissolution studies pH solubility p
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High Permeability Low SOLUBILITY CH
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is evident form the fact [51] that
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independent of initial drug concent
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STABILITY CHARACTERISTICS 969 drug
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6.2.5 CONCLUSIONS Preformulation te
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REFERENCES 973 16. Huang , L. , and
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54. 55. 56. REFERENCES 975 IFAMA (
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978 TABLET DESIGN 6.3.9.3 Case Stud
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980 TABLET DESIGN Another reason, t
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982 TABLET DESIGN E: This ensures t
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984 TABLET DESIGN substance would b
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986 TABLET DESIGN Plasticity 1.0 0.
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988 TABLET DESIGN Drug release (%)
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990 TABLET DESIGN FIGURE 9 Dissolut
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992 TABLET DESIGN TABLE 2 Number 1
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994 TABLET DESIGN Formulation Table
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996 TABLET DESIGN TABLE 4 Theophyll
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998 TABLET DESIGN often very fi ne,
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1000 TABLE 6 Formulations by Wet Gr
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1002 TABLET DESIGN 6.3.6.2 FIGURE 1
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1004 TABLET DESIGN TABLE 9 Papaveri
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1006 TABLET DESIGN TABLE 12 Weight
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1008 TABLET DESIGN (3.179 and 4.500
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1010 TABLET DESIGN TABLE 14 Run Ord
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1012 TABLET DESIGN Regression coeff
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1014 TABLET DESIGN to being the out
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1016 TABLET DESIGN Mechanical Prope
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1018 TABLET DESIGN drawbacks (unsaf
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1020 TABLET DESIGN TABLE 16 Basic F
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1022 TABLET DESIGN PEG (e.g., Macro
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1024 TABLET DESIGN 0.45% 0.40% 0.35
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1026 TABLET DESIGN FIGURE 34 Granul
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1028 TABLET DESIGN TABLE 19 SEPIFIL
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1030 TABLET DESIGN (c) Blistering D
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1032 TABLET DESIGN % Dextromethorph
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1034 TABLET DESIGN (a) (b) 500 μm
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1036 TABLET DESIGN threshold p c1 a
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1038 TABLET DESIGN TABLE 24 Composi
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1040 TABLET DESIGN Korsmeyer - Pepp
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1042 TABLET DESIGN % Water uptake/d
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1044 TABLET DESIGN FIGURE 47 Temper
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1046 TABLET DESIGN REFERENCES 1. Un
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1048 TABLET DESIGN 34. Congreve , M
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1050 TABLET DESIGN 73. Miranda , A.
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6.4 TABLET PRODUCTION SYSTEMS Katha
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PHYSICS OF TABLET FORMATION 1055 en
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Tablet production systems can be op
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TABLETING MACHINES 1059 Eccentric T
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TABLETING MACHINES 1061 In Figure 4
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TABLETING MACHINE SIMULATORS (COMPA
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TABLETING MACHINE SIMULATORS (COMPA
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However, for mechanical compaction
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INSTRUMENTATION OF TABLETING MACHIN
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Force (kN) FIGURE 13 ANALYSIS OF TA
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TABLE 4 Source Emschermann [91] (Fi
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TABLE 6 Parameters Directly Deduced
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TABLE 7 Parameters Calculated from
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ANALYSIS OF TABLETING PROCESS 1079
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TABLE 8 Source 3D model [143, 144,
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6.4.11 SPECIAL ACCESSORIES OF TABLE
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usually tends to vary. However, the
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ing at punches and dies. Low produc
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REFERENCES 1089 24. Elamin , A. , S
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REFERENCES 1091 64. Yeh , C. , Alta
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REFERENCES 1093 100. Armstrong , N.
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REFERENCES 1095 140. Kuentz , M. ,
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REFERENCES 1097 178. Hauschild , K.
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6.5 CONTROLLED RELEASE OF DRUGS FRO
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INTRODUCTION 1101 ings, and their e
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needed to circulate them [57] . Typ
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APPLICATIONS 1105 stream. During dr
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APPLICATIONS 1107 TABLE 1 Theophyll
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APPLICATIONS 1109 FIGURE 1 Release
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(a) (b) APPLICATIONS 1111 FIGURE 3
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APPLICATIONS 1113 FIGURE 5 Ternary
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APPLICATIONS 1115 of the drug, dC/d
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APPLICATIONS 1117 FIGURE 9 Ternary
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Release rate (mg/min) 0.40 0.30 0.2
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REFERENCES REFERENCES 1121 1. Lange
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REFERENCES 1123 37. Lin , Y - K. ,
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REFERENCES 1125 73. St - Onge , L.
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REFERENCES 1127 107. Lai , J. - Y.
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APPENDIX 1129 FIGURE A3 Release of
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APPENDIX 1131 FIGURE A7 Release of
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6.6 TABLET COMPRESSION Helton M. M.
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during compression, which will also
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of powder mixtures is usually chara
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lose in combination with either tal
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Due to the signifi cant nonlinearit
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EQUIPMENT FOR TABLET COMPRESSION 11
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Product Fill cam (mm) column height
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TABLET PRESS TOOLING 1147 TABLE 1 T
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TABLET PRESS TOOLING 1149 7. Tungst
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FIGURE 6 Tooling standards confi gu
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6.6.7 TABLE ENGRAVING Engraving is
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Shallow and standard concave tablet
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is the most popular bisect confi gu
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PROBLEMS DURING TABLET MANUFACTURIN
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thus reducing a potential variation
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REFERENCES 1163 27. Train , D. ( 19
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1166 EFFECTS OF GRINDING IN PHARMAC
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1192 ORAL EXTENDED-RELEASE FORMULAT
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7.1 CYCLODEXTRIN - BASED NANOMATERI
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OH (3) OH (2) HOCH 2 HOCH 2 O O OH
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APPLICATIONS OF CYCLODEXTRINS IN NA
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Percentage of release 100 90 80 70
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O APPLICATIONS OF CYCLODEXTRINS IN
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β - CDC6 loaded with the model dru
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REFERENCES 1243 13. Stella , V. J.
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REFERENCES 1245 49. Dodziuk , H. ,
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REFERENCES 1247 81. Memi şo ğlu -
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1250 NANOTECHNOLOGY IN PHARMACEUTIC
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1290 PHARMACEUTICAL NANOSYSTEMS 7.3
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1292 PHARMACEUTICAL NANOSYSTEMS TAB
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1296 PHARMACEUTICAL NANOSYSTEMS Lam
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1298 PHARMACEUTICAL NANOSYSTEMS 7.3
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1300 PHARMACEUTICAL NANOSYSTEMS sta
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1304 PHARMACEUTICAL NANOSYSTEMS har
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1308 PHARMACEUTICAL NANOSYSTEMS Sur
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1310 PHARMACEUTICAL NANOSYSTEMS Aut
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1312 PHARMACEUTICAL NANOSYSTEMS ®
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1314 PHARMACEUTICAL NANOSYSTEMS 55.
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1316 PHARMACEUTICAL NANOSYSTEMS 100
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1324 PHARMACEUTICAL NANOSYSTEMS Nan
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7.4 OIL - IN - WATER NANOSIZED EMUL
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GENERATIONS OF OIL-IN-WATER NANOSIZ
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DRUG-FREE/LOADED OIL-IN-WATER NANOS
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EXCIPIENT INCLUSION: OIL-IN-WATER N
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EXCIPIENT INCLUSION: OIL-IN-WATER N
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MEDICAL APPLICATIONS OF OIL-IN-WATE
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evaluation of the lipid hydroperoxi
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REFERENCES 1357 21. Ott , G. , Sing
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REFERENCES 1359 57. Harris , J. M.
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REFERENCES 1361 94. Kim , Y. J. , K
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REFERENCES 1363 131. Swietlikowska
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REFERENCES 1365 167. Acheampong , A
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INDEX Abortifacients, 850 Acyclovir
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Lung cancer, 497-502 Lung toxicity,
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