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06 Route of administration and dosage forms.pdf
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Ibrahim Abdullah
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06 Route of administration and dosage forms.pdf
1.
WŚĂƌŵĂĐLJWƌĂĐƚŝĐĞ/ ZKhd^K D/E/^dZd/KE Θ K^' KZD^ ,WdZ Ϭϲ ĞůŝǀĞƌĞĚďLJ/ďƌĂŚŝŵďŝŶďĚƵůůĂŚ͕^W,͕D^h /($51Ζ1*28720(6 ŽƌƌĞůĂƚĞ ƚŚĞ ĚŽƐĂŐĞĨŽƌŵƐ ǁŝƚŚƚŚĞ ĂƉƉƌŽƉƌŝĂƚĞ ƌŽƵƚĞŽĨ ĂĚŵŝŶŝƐƚƌĂƚŝŽŶ ĞƐĐƌŝďĞ ǀĂƌŝŽƵƐĚŽƐĂŐĞ ĨŽƌŵƐĂǀĂŝůĂďůĞ ĨŽƌŵĞĚŝĐĂƚŝŽŶƐ ĂŶĚĞdžƉůĂŝŶ ƌŽƵƚĞƐŽĨ ĂĚŵŝŶŝƐƚƌĂƚŝŽŶ WĂƚŚ
ďLJǁŚŝĐŚĂĚƌƵŐ͕ĨůƵŝĚ͕ƉŽŝƐŽŶŽƌ ŽƚŚĞƌƐƵďƐƚĂŶĐĞŝƐďƌŽƵŐŚƚŝŶƚŽĐŽŶƚĂĐƚ ǁŝƚŚƚŚĞďŽĚLJ ƐƵďƐƚĂŶĐĞŵƵƐƚďĞƚƌĂŶƐƉŽƌƚĞĚĨƌŽŵ ƚŚĞƐŝƚĞŽĨĞŶƚƌLJƚŽƚŚĞƉĂƌƚŽĨƚŚĞďŽĚLJ ǁŚĞƌĞŝƚƐĂĐƚŝŽŶŝƐĚĞƐŝƌĞĚ dŚĞƉŚĂƌŵĂĐŽŬŝŶĞƚŝĐƉƌŽƉĞƌƚŝĞƐŽĨĂ ĚƌƵŐ͕D;ĂďƐŽƌƉƚŝŽŶ͕ĚŝƐƚƌŝďƵƚŝŽŶ͕ ŵĞƚĂďŽůŝƐŵĂŶĚĞůŝŵŝŶĂƚŝŽŶͿĂƌĞ ŝŶĨůƵĞŶĐĞĚďLJƚŚĞƌŽƵƚĞŽĨĂĚŵŝŶŝƐƚƌĂƚŝŽŶ 5287(6ŽĨ $'0,1,675$7,21 ŝŶƚƌŽĚƵĐƚŝŽŶ D/d/KEWZKWZd/^ oŽŶĐĞŶƚƌĂƚŝŽŶŝŶďůŽŽĚ oDĂŐŶŝƚƵĚĞŽĨĞĨĨĞĐƚ oŵŽƵŶƚƚŽďĞĚĞůŝǀĞƌĞĚ d/D oZĂƉŝĚŝƚLJŽĨŽŶƐĞƚ oƵƌĂƚŝŽŶŽĨĞĨĨĞĐƚƐ Wd/Ed͛^,ZdZ/^d/^ oŐĞ oWŚLJƐŝĐĂůΘŵĞŶƚĂůƐƚĂƚƵƐ 5287(6ŽĨ $'0,1,675$7,21 ƐĞůĞĐƚŝŽŶĐƌŝƚĞƌŝĂ
2.
5287(6ŽĨ$'0,1,675$7,21 ƚŚƌĞĞŵĂŝŶŐƌŽƵƉƐ ydZE ůŽĐĂů ĞĨĨĞĐƚ͕ƐƵďƐƚĂŶĐĞŝƐ ĂƉƉůŝĞĚĚŝƌĞĐƚůLJǁŚĞƌĞ ŝƚƐĂĐƚŝŽŶŝƐĚĞƐŝƌĞĚ EdZ ĚĞƐŝƌĞĚĞĨĨĞĐƚŝƐ ƐLJƐƚĞŵŝĐ;ŶŽŶͲůŽĐĂůͿ͕ ƐƵďƐƚĂŶĐĞŝƐŐŝǀĞŶǀŝĂ ƚŚĞĚŝŐĞƐƚŝǀĞƚƌĂĐƚ WZEdZ ĚĞƐŝƌĞĚĞĨĨĞĐƚŝƐ ƐLJƐƚĞŵŝĐ͕ƐƵďƐƚĂŶĐĞŝƐ ŐŝǀĞŶďLJŽƚŚĞƌƌŽƵƚĞƐ ƚŚĂŶƚŚĞĚŝŐĞƐƚŝǀĞƚƌĂĐƚ dŽƉŝĐĂůͲ ƉŝĐƵƚĂŶĞŽƵƐ ƌĞĂŵƐ͕ŽŝŶƚŵĞŶƚƐ /ŶŚĂůĂƚŝŽŶĂů ƐƚŚŵĂŵĞĚŝĐĂƚŝŽŶƐ LJĞĚƌŽƉƐ ŽƌĐŽŶũƵŶĐƚŝǀŝƚŝƐ ĂƌĚƌŽƉƐ ŶƚŝďŝŽƚŝĐƐ͕ĐŽƌƚŝĐŽƐƚĞƌŽŝĚƐ /ŶƚƌĂŶĂƐĂůƌŽƵƚĞ ĞĐŽŶŐĞƐƚĂŶƚ sĂŐŝŶĂů ƐƚƌŽŐĞŶƐ͕ĂŶƚŝĨƵŶŐĂůƐ NxpNl_A] dŽƉŝĐĂůͲ
ƉŝĐƵƚĂŶĞŽƵƐ ƌĞĂŵƐ͕ŽŝŶƚŵĞŶƚƐ /ŶŚĂůĂƚŝŽŶĂů ƐƚŚŵĂŵĞĚŝĐĂƚŝŽŶƐ LJĞĚƌŽƉƐ ŽƌĐŽŶũƵŶĐƚŝǀŝƚŝƐ ĂƌĚƌŽƉƐ ŶƚŝďŝŽƚŝĐƐ͕ĐŽƌƚŝĐŽƐƚĞƌŽŝĚƐ /ŶƚƌĂŶĂƐĂůƌŽƵƚĞ ĞĐŽŶŐĞƐƚĂŶƚ sĂŐŝŶĂů ƐƚƌŽŐĞŶƐ͕ĂŶƚŝĨƵŶŐĂůƐ NxpNl_A] dŽƉŝĐĂůͲ ƉŝĐƵƚĂŶĞŽƵƐ ƌĞĂŵƐ͕ŽŝŶƚŵĞŶƚƐ /ŶŚĂůĂƚŝŽŶĂů ƐƚŚŵĂŵĞĚŝĐĂƚŝŽŶƐ LJĞĚƌŽƉƐ ŽƌĐŽŶũƵŶĐƚŝǀŝƚŝƐ ĂƌĚƌŽƉƐ ŶƚŝďŝŽƚŝĐƐ͕ĐŽƌƚŝĐŽƐƚĞƌŽŝĚƐ /ŶƚƌĂŶĂƐĂůƌŽƵƚĞ ĞĐŽŶŐĞƐƚĂŶƚ sĂŐŝŶĂů ƐƚƌŽŐĞŶƐ͕ĂŶƚŝĨƵŶŐĂůƐ NxpNl_A]
3.
dŽƉŝĐĂůͲ ƉŝĐƵƚĂŶĞŽƵƐ ƌĞĂŵƐ͕ŽŝŶƚŵĞŶƚƐ /ŶŚĂůĂƚŝŽŶĂů ƐƚŚŵĂŵĞĚŝĐĂƚŝŽŶƐ LJĞĚƌŽƉƐ ŽƌĐŽŶũƵŶĐƚŝǀŝƚŝƐ ĂƌĚƌŽƉƐ ŶƚŝďŝŽƚŝĐƐ͕ĐŽƌƚŝĐŽƐƚĞƌŽŝĚƐ /ŶƚƌĂŶĂƐĂůƌŽƵƚĞ ĞĐŽŶŐĞƐƚĂŶƚ sĂŐŝŶĂů ƐƚƌŽŐĞŶƐ͕ĂŶƚŝĨƵŶŐĂůƐ NxpNl_A] dŽƉŝĐĂůͲ ƉŝĐƵƚĂŶĞŽƵƐ ƌĞĂŵƐ͕ŽŝŶƚŵĞŶƚƐ /ŶŚĂůĂƚŝŽŶĂů ƐƚŚŵĂŵĞĚŝĐĂƚŝŽŶƐ LJĞĚƌŽƉƐ ŽƌĐŽŶũƵŶĐƚŝǀŝƚŝƐ ĂƌĚƌŽƉƐ ŶƚŝďŝŽƚŝĐƐ͕ĐŽƌƚŝĐŽƐƚĞƌŽŝĚƐ /ŶƚƌĂŶĂƐĂůƌŽƵƚĞ ĞĐŽŶŐĞƐƚĂŶƚ sĂŐŝŶĂů ƐƚƌŽŐĞŶƐ͕ĂŶƚŝĨƵŶŐĂůƐ NxpNl_A] dŽƉŝĐĂůͲ
ƉŝĐƵƚĂŶĞŽƵƐ ƌĞĂŵƐ͕ŽŝŶƚŵĞŶƚƐ /ŶŚĂůĂƚŝŽŶĂů ƐƚŚŵĂŵĞĚŝĐĂƚŝŽŶƐ LJĞĚƌŽƉƐ ŽƌĐŽŶũƵŶĐƚŝǀŝƚŝƐ ĂƌĚƌŽƉƐ ŶƚŝďŝŽƚŝĐƐ͕ĐŽƌƚŝĐŽƐƚĞƌŽŝĚƐ /ŶƚƌĂŶĂƐĂůƌŽƵƚĞ ĞĐŽŶŐĞƐƚĂŶƚ sĂŐŝŶĂů ƐƚƌŽŐĞŶƐ͕ĂŶƚŝĨƵŶŐĂůƐ NxpNl_A] EdZ
4.
EdZ zDKhd, Ͳ ƉŽƉƵůĂƌ Ͳ ƚĂďůĞƚƐ͕ĐĂƉƐƵůĞƐŽƌĚƌŽƉƐ s/'^dZ//E'dh Ͳ
ĚƌƵŐƐĂŶĚĞŶƚĞƌĂůŶƵƚƌŝƚŝŽŶ Zdz Ͳ ǀĂƌŝŽƵƐĚƌƵŐƐŝŶƐƵƉƉŽƐŝƚŽƌLJŽƌĞŶĞŵĂ EdZ zDKhd, Ͳ ƉŽƉƵůĂƌ Ͳ ƚĂďůĞƚƐ͕ĐĂƉƐƵůĞƐŽƌĚƌŽƉƐ s/'^dZ//E'dh Ͳ ĚƌƵŐƐĂŶĚĞŶƚĞƌĂůŶƵƚƌŝƚŝŽŶ Zdz Ͳ ǀĂƌŝŽƵƐĚƌƵŐƐŝŶƐƵƉƉŽƐŝƚŽƌLJŽƌĞŶĞŵĂ EdZ zDKhd, Ͳ ƉŽƉƵůĂƌ Ͳ ƚĂďůĞƚƐ͕ĐĂƉƐƵůĞƐŽƌĚƌŽƉƐ s/'^dZ//E'dh Ͳ ĚƌƵŐƐĂŶĚĞŶƚĞƌĂůŶƵƚƌŝƚŝŽŶ Zdz Ͳ ǀĂƌŝŽƵƐĚƌƵŐƐŝŶƐƵƉƉŽƐŝƚŽƌLJŽƌĞŶĞŵĂ WZEdZ
5.
WZEdZ WZEdZ ^ƵďĐƵƚĂŶĞŽƵƐ ƵŶĚĞƌƚŚĞƐŬŝŶʹ ŝŶƐƵůŝŶ /ŶƚƌĂĚĞƌŵĂů ŝŶƚŽƚŚĞƐŬŝŶŝƚƐĞůĨʹ ƐŬŝŶ ƚĞƐƚŝŶŐƐŽŵĞĂůůĞƌŐĞŶƐ͕ ĂŶĚĂůƐŽĨŽƌƚĂƚƚŽŽƐ /ŶƚƌĂǀĞŶŽƵƐ ŝŶƚŽĂǀĞŝŶʹ
ĚƌƵŐƐ͕ ƉĂƌĞŶƚĞƌĂůŶƵƚƌŝƚŝŽŶ /ŶƚƌĂĂƌƚĞƌŝĂů ŝŶƚŽĂŶĂƌƚĞƌLJʹ ǀĂƐŽĚŝůĂƚŽƌĚƌƵŐƐ;ĨŽƌ ǀĂƐŽƐƉĂƐŵͿ͕ƚŚƌŽŵďŽůLJƚŝĐ ĚƌƵŐƐ;ĨŽƌĞŵďŽůŝƐŵͿ /ŶƚƌĂŵƵƐĐƵůĂƌ ŝŶƚŽĂŵƵƐĐůĞʹ ǀĂĐĐŝŶĞƐ͕ ĂŶƚŝďŝŽƚŝĐƐ͕ĂŶĚůŽŶŐͲƚĞƌŵ ƉƐLJĐŚŽĂĐƚŝǀĞĂŐĞŶƚƐ WZEdZ ƉŝĚƵƌĂůͬƉĞƌŝĚƵƌĂů ŝŶũĞĐƚŝŽŶŽƌŝŶĨƵƐŝŽŶŝŶƚŽ ƚŚĞĞƉŝĚƵƌĂůƐƉĂĐĞʹ ĞƉŝĚƵƌĂůĂŶĞƐƚŚĞƐŝĂ /ŶƚƌĂƉĞƌŝƚŽŶĞĂů ŝŶĨƵƐŝŽŶŽƌŝŶũĞĐƚŝŽŶŝŶƚŽ ƚŚĞƉĞƌŝƚŽŶĞƵŵʹ ƉĞƌŝƚŽŶĞĂůĚŝĂůLJƐŝƐ /ŶƚƌĂƚŚĞĐĂů ŝŶƚŽƚŚĞƐƉŝŶĂůĐĂŶĂůʹ ĐŽŵŵŽŶůLJƵƐĞĚĨŽƌ ƐƉŝŶĂůĂŶĞƐƚŚĞƐŝĂĂŶĚ ĐŚĞŵŽƚŚĞƌĂƉLJ /ŶƚƌĂĐĂƌĚŝĂĐ ŝŶƚŽƚŚĞŚĞĂƌƚʹ ĂĚƌĞŶĂůŝŶĞĚƵƌŝŶŐ ĐĂƌĚŝŽƉƵůŵŽŶĂƌLJ ƌĞƐƵƐĐŝƚĂƚŝŽŶ;ŶŽƚ ĐŽŵŵŽŶͿ /ŶƚƌĂŽƐƐĞŽƵƐ /ŶĨƵƐŝŽŶŝŶƚŽƚŚĞďŽŶĞŵĂƌƌŽǁʹ ĂŶŝŶĚŝƌĞĐƚ ŝŶƚƌĂǀĞŶŽƵƐĂĐĐĞƐƐďĞĐĂƵƐĞƚŚĞďŽŶĞ ŵĂƌƌŽǁĚƌĂŝŶƐĚŝƌĞĐƚůLJŝŶƚŽƚŚĞǀĞŶŽƵƐ ƐLJƐƚĞŵ͖ŽĐĐĂƐŝŽŶĂůůLJƵƐĞĚĨŽƌĚƌƵŐƐĂŶĚ ĨůƵŝĚƐŝŶĞŵĞƌŐĞŶĐLJŵĞĚŝĐŝŶĞĂŶĚƉĂĞĚŝĂƚƌŝĐƐ ǁŚĞŶŝŶƚƌĂǀĞŶŽƵƐĂĐĐĞƐƐŝƐĚŝĨĨŝĐƵůƚ ĂĐŚƌŽƵƚĞŚĂƐŝƚƐ sEd'^ ĂŶĚ /^sEd'^
6.
dKW/ ĚǀĂŶƚĂŐĞƐ WƌŽǀŝĚĞƐůŽĐĂůĞĨĨĞĐƚ ^ŽŵĞĚƌƵŐĐĂŶƉƌŽǀŝĚĞ ƐLJƐƚĞŵŝĐĞĨĨĞĐƚ ĞǁƐŝĚĞĞĨĨĞĐƚ ;ĞdžĐĞƉƚ ĐŽƌƚŝĐŽƐƚĞƌŽŝĚƐͿ ŝƐĂĚǀĂŶƚĂŐĞƐ DĞƐƐLJ;ŽŝŶƚŵĞŶƚͿ ĐĐŝĚĞŶƚĂůůLJŐŝǀĞƐLJƐƚĞŵŝĐ ĞĨĨĞĐƚǁŚĞŶĂƉƉůLJƚŽŽƉĞŶ ǁŽƵŶĚͬĂďƌĂƐŝŽŶ €dƌĂŶƐĚĞƌŵĂů ĂĚŵŝŶŝƐƚƌĂƚŝŽŶŝƐĂĐŽŵĨŽƌƚĂďůĞ ĂůƚĞƌŶĂƚŝǀĞ͖ƚŚĞƌĞĂƌĞ͕ŚŽǁĞǀĞƌ͕ŽŶůLJĂĨĞǁĚƌƵŐ ƉƌĞƉĂƌĂƚŝŽŶƐƐƵŝƚĂďůĞĨŽƌƚƌĂŶƐĚĞƌŵĂůĂĚŵŝŶŝƐƚƌĂƚŝŽŶ /E,d/KE ĚǀĂŶƚĂŐĞƐ ͺƐƚͺͺƚŵĞƚŚŽĚ͕ϳͲϭϬ ƐĞĐŽŶĚƐĨŽƌƚŚĞĚƌƵŐƚŽƌĞĂĐŚ ƚŚĞďƌĂŝŶ ͺĐͺůĞĨĨĞĐƚ;ĨĞǁĞƌƐŝĚĞ ĞĨĨĞĐƚƐͿ͘sĞŶƚŽůŝŶϭϬϬŵĐŐǀƐ ƚĂďůĞƚϰ͕ϬϬϬŵĐŐ;ϰŵŐͿ EŽĨŝƌƐƚƉͺƐƐĞĨĨĞĐƚ ŝƐĂĚǀĂŶƚĂŐĞƐ DŽƐƚĂĚĚŝĐƚŝǀĞ
ƌŽƵƚĞŽĨ ĂĚŵŝŶŝƐƚƌĂƚŝŽŶďĞĐĂƵƐĞŝƚŚŝƚƐ ƚŚĞďͺĂͺŶ ƐŽƋƵŝĐŬůLJ ŝĨĨŝĐƵůƚŝĞƐŝŶƌĞŐƵůĂƚŝŶŐƚŚĞ ĞdžĂĐƚĂŵŽƵŶƚŽĨĚŽƐĂŐĞ͘ ͞DĞƚĞƌĞĚ͟ĚĞǀŝĐĞƐŽǀĞƌĐŽŵĞ ƚŚŝƐ WĂƚŝĞŶƚŚĂǀŝŶŐĚŝĨĨŝĐƵůƚŝĞƐŝŶ ŐŝǀŝŶŐƚŚĞŵƐĞůǀĞƐĂĚƌƵŐďLJ ŝŶŚĂůĞƌ͘ŽŽƌĚŝŶĂƚŝŽŶ ŝƐƐƵĞ͘ KZ ĚǀĂŶƚĂŐĞƐ DŽƐƚĐͺͺǀͺŶͺͺͺƚ͕ƉŽƉƵůĂƌĂƐŶŽ ƉƵŶĐƚƵƌĞƐŽƌƐƚĞƌŝůĞƉƌŽĐĞĚƵƌĞƐĂƌĞ ŶĞĐĞƐƐĂƌLJ ^ĂĨĞ͕ĚŽĞƐŶŽƚďƌĞĂŬƐŬŝŶďĂͺͺŝͺƌ ĂƐLJƚŽĂĚŵŝŶŝƐƚĞƌ ŝƐĂĚǀĂŶƚĂŐĞƐ /ŶĂƉƉƌŽƉƌŝĂƚĞĨŽƌŶͺƵƐͺĂ ƉĂƚŝĞŶƚ hŶƉůĞĂƐĂŶƚƚĂƐƚĞ /ŶĂƉƉƌŽƉƌŝĂƚĞǁŚĞŶ'/dŚĂƐƌĞĚƵĐĞĚ ŵŽƚͺůͺƚLJ /ŶĂƉƉƌŽƉƌŝĂƚĞǁŚĞŶĐĂŶŶŽƚƐǁͺůͺͺǁ DĂLJŝƌƌŝƚĂƚĞ'/d;E^/ƐͿ ^h/E'h ĚǀĂŶƚĂŐĞƐ ^ĂŵĞĂƐŽƌĂů ŽĐĂůĞĨĨĞĐƚ;ůŽnjĞŶŐĞƐͿ ZĂƉŝĚůLJĂďƐŽƌďĞĚ 'ƌĞĂƚĞƌƉŽƚĞŶĐLJ ŝƐĂĚǀĂŶƚĂŐĞƐ /ĨĂĐĐŝĚĞŶƚĂůůLJƐǁĂůůŽǁ͕ĚƌƵŐ ŶŽƚĂĐƚŝǀĞ DƵƐƚƌĞŵĂŝŶƵŶĚĞƌƚŽŶŐƵĞ ƵŶƚŝůĚͺƐƐŽͺǀĞ
7.
ZdͬW^^Zz ĚǀĂŶƚĂŐĞƐ ĂŶďĞƵƐĞĚǁŚĞŶĐĂŶŶŽƚƐǁĂůůŽǁ͕ ďĂĚůLJƚĂƐƚĞ ƌƵŐƌĞůĞĂƐĞĚĂƚƐůŽǁƐƚĞĂĚLJƐƚĂƚĞ ŽĐĂůĞĨĨĞĐƚͬ^LJƐƚĞŵŝĐĞĨĨĞĐƚ ŝƐĂĚǀĂŶƚĂŐĞƐ ŽƐĞĂďƐŽƌƉƚŝŽŶƵͺƉͺ ͺĚŝͺƚĂͺͺĞ DĞƐƐLJ /E:d/KE ĚǀĂŶƚĂŐĞƐ ĂƐƚ͗ϭϱͲϯϬƐĞĐŽŶĚƐĨŽƌ/s͕ϯͲϱŵŝŶƵƚĞƐ ĨŽƌ/DĂŶĚƐƵďĐƵƚĂŶĞŽƵƐʹ /sƵƐĞĚŝŶ ĂĐƵƚĞ͕ĞŵĞƌŐĞŶĐLJĂŶĚŝŶƚĞŶƐŝǀĞĐĂƌĞ KŶĞŝŶũĞĐƚŝŽŶĐĂŶďĞĨŽƌŵƵůĂƚĞĚƚŽůĂƐƚ ĚĂLJƐŽƌĞǀĞŶŵŽŶƚŚƐ͕Ğ͘Ő͘ĞƉŽͲWƌŽǀĞƌĂ ŝƐĂďŝƌƚŚĐŽŶƚƌŽůƐŚŽƚƚŚĂƚǁŽƌŬƐĨŽƌ ƚŚƌĞĞŵŽŶƚŚƐ /sĐĂŶĚĞůŝǀĞƌĐŽŶƚŝŶƵŽƵƐŵĞĚŝĐĂƚŝŽŶ͕ Ğdž͘DŽƌƉŚŝŶĞĨŽƌƉĂƚŝĞŶƚƐŝŶĐŽŶƚŝŶƵŽƵƐ ƉĂŝŶ͕ŽƌƐĂůŝŶĞĚƌŝƉĨŽƌƉĞŽƉůĞŶĞĞĚŝŶŐ ĨůƵŝĚƐ EŽĨŝƌƐƚƉĂƐƐĞĨĨĞĐƚ ŝƐĂĚǀĂŶƚĂŐĞƐ ĞĐĂƵƐĞŝƚΖƐĨĂƐƚ͕ƚŚĞƌĞŝƐŵŽƌĞƌŝƐŬŽĨ ĂĚĚŝĐƚŝŽŶ ǁŚĞŶŝƚĐŽŵĞƐƚŽŝŶũĞĐƚŝŶŐ ĚƌƵŐƐŽĨĂďƵƐĞ /ĨŶĞĞĚůĞƐĂƌĞƐŚĂƌĞĚ͕ƚŚĞƌĞŝƐƌŝƐŬŽĨ,/s ĂŶĚŽƚŚĞƌŝŶĨĞĐƚŝŽƵƐĚŝƐĞĂƐĞƐ DŽƐƚĚĂŶŐĞƌŽƵƐZKďĞĐĂƵƐĞŝƚďLJƉĂƐƐĞƐŵŽƐƚŽĨƚŚĞ ďŽĚLJΖƐŶĂƚƵƌĂůĚĞĨĞŶĐĞƐ͕ĞdžƉŽƐŝŶŐƚŚĞƵƐĞƌƚŽŚĞĂůƚŚ ƉƌŽďůĞŵƐƐƵĐŚĂƐŚĞƉĂƚŝƚŝƐ͕ĂďƐĐĞƐƐĞƐ͕ŝŶĨĞĐƚŝŽŶƐ͕ĂŶĚ ƵŶĚŝƐƐŽůǀĞĚƉĂƌƚŝĐůĞƐŽƌĂĚĚŝƚŝǀĞƐ /ĨŶŽƚĚŽŶĞƉƌŽƉĞƌůLJ͕ĂŝƌďŽůƵƐĞƐ;ďƵďďůĞƐͿ ĐĂŶŽĐĐƵƌĂŶĚĐĂŶďĞĨĂƚĂů EĞĞĚŽĨƐƚƌŝĐƚĂƐĞƉƐŝƐ /E:d/KE;ƐĐͿ ĚǀĂŶƚĂŐĞƐ
ŝƐĂĚǀĂŶƚĂŐĞƐ ^ƚͺƌͺͺĞ ƚĞĐŚŶŝƋƵĞŶĞĞĚĞĚ džƉĞŶƐŝǀĞ WĂŝŶ DĂLJĐĂƵƐĞ ĂŶdžŝĞƚLJ KŶƐĞƚĨĂƐƚĞƌ ĂŶĂĚŵŝŶŝƐƚĞƌďLJ ƉĂƚŝĞŶƚŚŝŵƐĞůĨ
8.
€^ŽŵĞƌŽƵƚĞƐĐĂŶďĞƵƐĞĚĨŽƌƚŽƉŝĐĂůĂƐǁĞůůĂƐƐLJƐƚĞŵŝĐ ƉƵƌƉŽƐĞƐ͕ĚĞƉĞŶĚŝŶŐŽŶƚŚĞĐŝƌĐƵŵƐƚĂŶĐĞƐ ŽƌĞdžĂŵƉůĞ͕ŝŶŚĂůĂƚŝŽŶŽĨĂƐƚŚŵĂĚƌƵŐƐŝƐƚĂƌŐĞƚĞĚĂƚƚŚĞĂŝƌǁĂLJƐ ;ƚŽƉŝĐĂůĞĨĨĞĐƚͿ͕ǁŚĞƌĞĂƐŝŶŚĂůĂƚŝŽŶŽĨǀŽůĂƚŝůĞĂŶĞƐƚŚĞƚŝĐƐŝƐƚĂƌŐĞƚĞĚ ĂƚƚŚĞďƌĂŝŶ;ƐLJƐƚĞŵŝĐĞĨĨĞĐƚͿ €KŶƚŚĞŽƚŚĞƌŚĂŶĚ͕ŝĚĞŶƚŝĐĂůĚƌƵŐƐĐĂŶƉƌŽĚƵĐĞĚŝĨĨĞƌĞŶƚ ƌĞƐƵůƚƐĚĞƉĞŶĚŝŶŐŽŶƚŚĞƌŽƵƚĞŽĨĂĚŵŝŶŝƐƚƌĂƚŝŽŶ ŽƌĞdžĂŵƉůĞ͕ƐŽŵĞĚƌƵŐƐĂƌĞŶŽƚƐŝŐŶŝĨŝĐĂŶƚůLJĂďƐŽƌďĞĚŝŶƚŽƚŚĞ ďůŽŽĚƐƚƌĞĂŵĨƌŽŵƚŚĞŐĂƐƚƌŽŝŶƚĞƐƚŝŶĂůƚƌĂĐƚĂŶĚƚŚĞŝƌĂĐƚŝŽŶĂĨƚĞƌ ĞŶƚĞƌĂůĂĚŵŝŶŝƐƚƌĂƚŝŽŶŝƐƚŚĞƌĞĨŽƌĞĚŝĨĨĞƌĞŶƚĨƌŽŵƚŚĂƚĂĨƚĞƌ ƉĂƌĞŶƚĞƌĂůĂĚŵŝŶŝƐƚƌĂƚŝŽŶ €dŚŝƐĐĂŶďĞŝůůƵƐƚƌĂƚĞĚďLJƚŚĞĂĐƚŝŽŶŽĨŶĂůŽdžŽŶĞ;EĂƌĐĂŶͿ͕ĂŶ ĂŶƚĂŐŽŶŝƐƚŽĨŽƉŝĂƚĞƐƐƵĐŚĂƐŵŽƌƉŚŝŶĞ EĂůŽdžŽŶĞĐŽƵŶƚĞƌĂĐƚƐŽƉŝĂƚĞĂĐƚŝŽŶŝŶƚŚĞĐĞŶƚƌĂůŶĞƌǀŽƵƐƐLJƐƚĞŵ ǁŚĞŶŐŝǀĞŶŝŶƚƌĂǀĞŶŽƵƐůLJĂŶĚŝƐƚŚĞƌĞĨŽƌĞƵƐĞĚŝŶƚŚĞƚƌĞĂƚŵĞŶƚŽĨ ŽƉŝĂƚĞŽǀĞƌĚŽƐĞ dŚĞƐĂŵĞĚƌƵŐ͕ǁŚĞŶƐǁĂůůŽǁĞĚ͕ĂĐƚƐĞdžĐůƵƐŝǀĞůLJŽŶƚŚĞďŽǁĞůƐ͖ŝƚŝƐ ŚĞƌĞƵƐĞĚƚŽƚƌĞĂƚĐŽŶƐƚŝƉĂƚŝŽŶƵŶĚĞƌŽƉŝĂƚĞƉĂŝŶƚŚĞƌĂƉLJĂŶĚĚŽĞƐ ŶŽƚĂĨĨĞĐƚƚŚĞƉĂŝŶͲƌĞĚƵĐŝŶŐĞĨĨĞĐƚŽĨƚŚĞŽƉŝĂƚĞ K^' KZD^ €ĚŽƐĂŐĞĨŽƌŵ ŝƐƚŚĞƉŚLJƐŝĐĂůĨŽƌŵŽĨĂĚŽƐĞŽĨ ŵĞĚŝĐĂƚŝŽŶ͕ƐƵĐŚĂƐĂĐĂƉƐƵůĞŽƌŝŶũĞĐƚŝŽŶ €dŚĞƌŽƵƚĞŽĨĂĚŵŝŶŝƐƚƌĂƚŝŽŶŝƐĚĞƉĞŶĚĞŶƚŽŶ ƚŚĞĚŽƐĂŐĞĨŽƌŵŽĨĂŐŝǀĞŶĚƌƵŐ €sĂƌŝŽƵƐĚŽƐĂŐĞĨŽƌŵƐŵĂLJĞdžŝƐƚĨŽƌƚŚĞƐĂŵĞ ĐŽŵƉŽƵŶĚ͕ƐŝŶĐĞĚŝĨĨĞƌĞŶƚŵĞĚŝĐĂůĐŽŶĚŝƚŝŽŶƐ ŵĂLJǁĂƌƌĂŶƚĚŝĨĨĞƌĞŶƚƌŽƵƚĞƐŽĨĂĚŵŝŶŝƐƚƌĂƚŝŽŶ͗ WĞƌƐŝƐƚĞŶƚǀŽŵŝƚŝŶŐŵĂLJŵĂŬĞŝƚĚŝĨĨŝĐƵůƚƚŽƵƐĞĂŶŽƌĂů ĚŽƐĂŐĞĨŽƌŵ͖ŝŶƚŚŝƐĐĂƐĞ͕ŝƚŵĂLJďĞĂĚǀŝƐĂďůĞƚŽƵƐĞ ĞŝƚŚĞƌĂŶŝŶũĞĐƚŝŽŶŽƌĂƐƵƉƉŽƐŝƚŽƌLJ ůƐŽ͕ƐƉĞĐŝĨŝĐĚŽƐĂŐĞĨŽƌŵƐŵĂLJďĞǁĂƌƌĂŶƚĞĚĨŽƌĐĞƌƚĂŝŶ ŵĞĚŝĐĂƚŝŽŶƐ͕ƐŝŶĐĞƚŚĞƌĞŵĂLJďĞƉƌŽďůĞŵƐǁŝƚŚƐƚĂďŝůŝƚLJ͕ Ğ͘Ő͘ŝŶƐƵůŝŶĐĂŶŶŽƚďĞŐŝǀĞŶŽƌĂůůLJƐŝŶĐĞŝƚŝƐĚŝŐĞƐƚĞĚďLJ ƚŚĞŐƵƚ K^' KZD^ • ^K/K^'KZD^͗ o
dĂďůĞƚ o WŽǁĚĞƌ • /Yh/K^'KZD^͗ o ^ŽůƵƚŝŽŶ o ^ƵƐƉĞŶƐŝŽŶ • ^D/Ͳ^K/K^'KZD^͗ o ƌĞĂŵ o KŝŶƚŵĞŶƚ • Kd,Z^͗ o ĞƌŽƐŽů
9.
KZK^' KZD^ • ^ŽůŝĚĚŽƐĂŐĞĨŽƌŵƐ͗ • dĂďůĞƚ •
ĂƉƐƵůĞ • WŽǁĚĞƌ • ŝƋƵŝĚĚŽƐĂŐĞĨŽƌŵƐ͗ • ^ŽůƵƚŝŽŶ • ^LJƌƵƉ • ^ƵƐƉĞŶƐŝŽŶ ddΘ W^h ddΘW^h ^h/E'hƚĂďůĞƚ
10.
/Yh/ ZdͬW^^Zz K^'KZD^ ;ƐĞŵŝͲƐŽůŝĚ͕ůŝƋƵŝĚͿ • ^ƵƉƉŽƐŝƚŽƌLJ • WĞƐƐĂƌLJ •
ŶĞŵĂ dKW/K^' KZD^ ;ůŝƋƵŝĚ͕ƐĞŵŝͲƐŽůŝĚ͕ƉĂƚĐŚͿ • ƌĞĂŵ • 'Ğů • ŝŶŝŵĞŶƚ • ŽƚŝŽŶ • KŝŶƚŵĞŶƚ • WĂƐƚĞ • dƌĂŶƐĚĞƌŵĂůƉĂƚĐŚ /E,d/KEK^'KZD^ • ĞƌŽƐŽů͕ŐĂƐ͕ƉŽǁĚĞƌ o DĞƚĞƌĞĚĚŽƐĞŝŶŚĂůĞƌ o ƌLJƉŽǁĚĞƌŝŶŚĂůĞƌ • ^ŽůƵƚŝŽŶĨŽƌŶĞďƵůŝnjĞƌ
11.
KW,d,D/ͬ Kd/ͬE^ K^'KZD^ • ŝƋƵŝĚ o ^ŽůƵƚŝŽŶ •
^ĞŵŝͲƐŽůŝĚ o ^ƵƐƉĞŶƐŝŽŶ o 'Ğů o KŝŶƚŵĞŶƚ • 'ĂƐ͕ĂĞƌŽƐŽů o ŶĂƐĂůƐƉƌĂLJ /E:d/KE K^' KZD^ • ^ŽůƵƚŝŽŶ • ^ƵƐƉĞŶƐŝŽŶ • ŵƵůƐŝŽŶ • ƌLJƉŽǁĚĞƌ;ƚŽďĞƌĞĐŽŶƐƚŝƚƵƚĞĚͿ dŚĂŶŬLJŽƵ ĨŽƌLJŽƵƌĂƚƚĞŶƚŝŽŶ
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