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Formulation and In-Vitro Characterization of Oseltamivir Fast Dissolving


Tablets Using Super Disintegrants

Article · October 2020


DOI: 10.36673/AJRCPS.2020.v08.i01.A07

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Atul Phatak Shrishail Ghurghure


P. E. S. Modern College of Pharmacy, Nigdi, Pune-411044 D.S.T.S. Mandal's College of Pharmacy, Jule Solapur Maharastra
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Formulation and In-Vitro Characterization of Oseltamivir Fast


Dissolving Tablets Using Super Disintegrants
R Y Patil1, Atul A Phatak2, Shrishail M Ghurghure1*, Sachin Yanjane1
Abstract: Š‡ƒ‹‘ˆ–Š‡’”‡•‡–•–—†›™ƒ•–‘ˆ‘”—Žƒ–‡ˆƒ•–†‹••‘Ž˜‹‰–ƒ„Ž‡–‘ˆ‘•‡Ž–ƒ‹˜‹”—•‹‰•—’‡”†‹•‹–‡‰”ƒ–•™‹–Š–Š‡
Š‡Ž’‘ˆ•‘Ž‹††‹•’‡”•‹‘–‡ Š‹“—‡–‘‹’”‘˜‡–Š‡ƒ“—‡‘—••‘Ž—„‹Ž‹–›ǡ†‹••‘Ž—–‹‘”ƒ–‡ƒ†–‘ˆƒ ‹Ž‹–ƒ–‡ˆƒ•–‡”‘•‡–‘ˆƒ –‹‘Ǥ‘Ž‹†
†‹•’‡”•‹‘ ‘ˆ ‘•‡Ž–ƒ‹˜‹” ™ƒ•’”‡’ƒ”‡† ™‹–Š  ͵Ͳ ‹ †‹ˆˆ‡”‡– †”—‰ǣ ƒ””‹‡” ”ƒ–‹‘—•‹‰ •‘Ž˜‡– ‡˜ƒ’‘”ƒ–‹‘ ‡–Š‘†•ǤŠ‡
‘’–‹‹œ‡†•‘Ž‹††‹•’‡”•‹‘ȋ†”—‰ǣ͵ͲǡͳǣͲǤͷ”ƒ–‹‘Ȍ™‡”‡ˆ—”–Š‡”—•‡†–‘’”‡’ƒ”‡ˆƒ•–†‹••‘Ž˜‹‰–ƒ„Ž‡–„›†‹”‡ – ‘’”‡••‹‘
‡–Š‘† —•‹‰ •—’‡”†‹•‹–‡‰”ƒ–• •— Š ƒ• ”‘•’‘˜‹†‘‡ ƒ† šƒ–Šƒ ‰—Ǥ ˆ”ƒ”‡† •’‡ –”‘• ‘’›ǡ †‹ˆˆ‡”‡–‹ƒŽ • ƒ‹‰
ƒŽ‘”‹‡–”› ƒ† šǦ”ƒ› †‹ˆˆ”ƒ –‹‘ ™‡”‡ ’‡”ˆ‘”‡† –‘ ‹†‡–‹ˆ› –Š‡ ’Š›•‹ ‘ Š‡‹ ƒŽ ‹–‡”ƒ –‹‘ „‡–™‡‡ †”—‰ ƒ† ‘’–‹‹œ‡†
ˆ‘”—Žƒ–‹‘Ǥ Š‡ ’”‡Ǧ ‘’”‡••‹‘ ’ƒ”ƒ‡–‡” ‘ˆ ’”‡’ƒ”‡† ’‘™†‡” „Ž‡†• ƒŽŽ ˆ‘”—Žƒ–‹‘ •—‰‰‡•–‡† ‰‘‘† ˆŽ‘™ƒ„‹Ž‹–› ƒ†
‘’”‡••‹„‹Ž‹–›Ǥ Š‡ ’”‡’ƒ”‡† –ƒ„Ž‡–• ™‡”‡ ‡˜ƒŽ—ƒ–‡† ˆ‘” –Š‹ ‡••ǡ Šƒ”†‡••ǡ ˆ”‹ƒ„‹Ž‹–› ƒ† ™‡‹‰Š– ˜ƒ”‹ƒ–‹‘ǡ †”—‰ ‘–‡–ǡ
™‡––‹‰–‹‡ǡ†‹•‹–‡‰”ƒ–‹‘–‹‡ƒ†in-vitro†‹••‘Ž—–‹‘•–—†‹‡•ǤŠ‡„ƒ– Š ͳʹǦ •Š‘™•Š‹‰Š‡•–”‡Ž‡ƒ•‡‘ˆͻͻǤͺ͹Ψ‹ʹͷ‹Ǥ

INTRODUCTION ‘Ž‹† †‹•’‡”•‹‘ ‘ˆ ‘•‡Ž–ƒ‹˜‹” ™ƒ• ’”‡’ƒ”‡† ™‹–Š 


ƒ„Ž‡– ‹• †‡ˆ‹‡† ƒ• ‘’”‡••‡† •‘Ž‹† †‘•ƒ‰‡ ˆ‘” ͵Ͳ ‹ †‹ˆˆ‡”‡– †”—‰ǣ ƒ””‹‡” ”ƒ–‹‘ —•‹‰ •‘Ž˜‡–
‘–ƒ‹‹‰ ‡†‹ ƒ‡– ™‹–Š ‘” ™‹–Š‘—– ‡š ‹’‹‡–•Ǥ  ‡˜ƒ’‘”ƒ–‹‘ ‡–Š‘†•Ǥ Š‡ ‘’–‹‹œ‡† •‘Ž‹† †‹•’‡”•‹‘
”‡ ‡– †‡ ƒ†‡•ǡ ƒ †‹ˆˆ—•‹‘ ‘ˆ ’Šƒ”ƒ ‡—–‹ ƒŽ ƒƒŽ›•‹• Šƒ• ȋ†”—‰ǣ  ͵Ͳǡ ͳǣͲǤͷ ”ƒ–‹‘Ȍ ™‡”‡ ˆ—”–Š‡” —•‡† –‘ ’”‡’ƒ”‡
„‡‡ ‘†— –‡† –‘ †‡˜‡Ž‘’ ‡™ ‹†‡ˆ‹‹–‡ “—ƒ–‹–› ˆ‘”•Ǥ ˆƒ•– †‹••‘Ž˜‹‰ –ƒ„Ž‡– „› †‹”‡ – ‘’”‡••‹‘ ‡–Š‘† —•‹‰
Š‡‘˜‡Ž†”—‰†‡Ž‹˜‡”›•›•–‡•ƒ”‡–‘‹ ”‡ƒ•‡•ƒˆ‡–›ƒ† •—’‡”†‹•‹–‡‰”ƒ–••— Šƒ• ”‘•’‘˜‹†‘‡ƒ†šƒ–Šƒ‰—Ǥ
‡ˆˆ‹ ƒ ›‘ˆ†”—‰„›ˆ‘”—Žƒ–‹‰ ‘˜‡‹‡–†‘•ƒ‰‡ˆ‘”ƒ† ˆ”ƒ”‡† •’‡ –”‘• ‘’› ƒ† †‹ˆˆ‡”‡–‹ƒŽ • ƒ‹‰
–‘ ƒ Š‹‡˜‡ „‡––‡” ’ƒ–‹‡– ‘’Ž‹ƒ ‡Ǥ ȏͳȐ Š‡ ƒ––‡” ‘ˆ ƒŽ‘”‹‡–”› ™‡”‡ ’‡”ˆ‘”‡† –‘ ‹†‡–‹ˆ› –Š‡
•™ƒŽŽ‘™‹‰ ‹• ƒŽ•‘ ƒ •–ƒ†ƒ”† †‡˜‡Ž‘’‡– –Š”‘—‰Š‘—– ƒ ’Š›•‹ ‘ Š‡‹ ƒŽ ‹–‡”ƒ –‹‘ „‡–™‡‡ †”—‰ ƒ† ‘’–‹‹œ‡†
‰‡”‹ƒ–”‹  ’ƒ–‹‡– „‡ ƒ—•‡ ‘ˆ ™‘””› ‘ˆ Š‘‹‰ǡ Šƒ† ˆ‘”—Žƒ–‹‘Ǥȏ͸Ǧ͹Ȑ
–”‡‘”•ǡ †›•’Šƒ•‹ƒ ƒ† ‹ ›‘—‰ ’‡‘’Ž‡ „‡ ƒ—•‡ ‘ˆ †˜ƒ–ƒ‰‡•‘ˆ ƒ•–‹••‘Ž˜‹‰ƒ„Ž‡–ǣȏ͵Ȑ
—†‡”†‡˜‡Ž‘’‡†—• —Žƒ”ƒ†‡”˜‘—••›•–‡•–Š‹•”‡•—Ž–• ͳǤ ’”‘˜‡† ‘’Ž‹ƒ ‡Ȁƒ††‡† ‘˜‡‹‡ ‡
‹ ƒ ’‘‘” ’ƒ–‹‡– ‘’Ž‹ƒ ‡ ™Š‹ Š ƒ› „‡ ‹’”‘˜‡† „› ʹǤ ‘™ƒ–‡”‡‡†‡†
–Š‡ ˆƒ•– †‹••‘Ž˜‹‰ –ƒ„Ž‡–•Ǥ ȏʹȐ Š‡ ‹†‡ƒŽ †”—‰ †‡Ž‹˜‡”› ͵Ǥ ‘ Š‡™‹‰‡‡†‡†
•›•–‡•Šƒ˜‡–™‘–Š‹‰•™‘—Ž†„‡‡‡†‡†ˆ‹”•–‹–‹‰Š–„‡ ͶǤ ‡––‡”–ƒ•–‡
‘‡ †‘•‡ –Š‡ ’‡”‹‘† ‘ˆ –”‡ƒ–‡– ™Š‡–Š‡” ‘” ‘– ‹–̵• ˆ‘” ͷǤ —‹–ƒ„Ž‡ˆ‘” ‘–”‘ŽŽ‡†ƒ•™‡ŽŽƒ•ˆƒ•–”‡Ž‡ƒ•‡ƒ –‹˜‡•
†ƒ›• ‘” ™‡‡ǡ Ž‹‡ ‹ˆ‡ –‹‘ǡ ‘” ˆ‘” –Š‡ Ž‹ˆ‡ –‹‡ ‘ˆ –Š‡ ͸Ǥ „‹Ž‹–› –‘ ’”‘†— ‡ „‡‡ˆ‹–• ‘ˆ Ž‹“—‹† ‡†‹ ƒ–‹‘ ™‹–Š‹
’ƒ–‹‡–ǡ ƒ• ‹ Š‹‰Š „Ž‘‘† ’”‡••—”‡ ‘” †‹ƒ„‡–‡•Ǥ ƒ•– –Š‡•–›Ž‡‘ˆ•‘Ž‹†’”‡’ƒ”ƒ–‹‘Ǥ
†‹••‘Ž˜‹‰ –ƒ„Ž‡–• ƒ”‡ ƒŽ•‘ ƒŽŽ‡† ƒ• ‘—–ŠǦ†‹••‘Ž˜‹‰ ͹Ǥ ŽŽ‘™•Š‹‰Š†”—‰Ž‘ƒ†‹‰Ǥ
–ƒ„Ž‡–•ǡ‡Ž–Ǧ‹‘—–Š–ƒ„Ž‡–•ǡ”ƒŽ†‹•’‡”•‹„Ž‡–ƒ„Ž‡–•ǡ”ƒ’ ͺǤ †ƒ’–ƒ„Ž‡ ƒ† ƒ‡ƒ„Ž‡ –‘ ‡š‹•–‹‰ ’”‘ ‡••‹‰ ƒ†
‡Ž–•ǡ ’‘”‘—• –ƒ„Ž‡–•ǡ “—‹  †‹••‘Ž˜‹‰ –ƒ„Ž‡–Ǥ ƒ•–
’ƒ ƒ‰‹‰ƒ Š‹‡”›
†‹••‘Ž˜‹‰–ƒ„Ž‡–•†‹••‘Ž˜‡‹–Š‡‘”ƒŽ ƒ˜‹–›™‹–Š‘—–™ƒ–‡”Ǥ
ͻǤ ‘•–Ǧ‡ˆˆ‡ –‹˜‡Ǥ
‘•– ˆƒ•– †‹••‘Ž˜‹‰ –ƒ„Ž‡–• Šƒ˜‡ •—„•–ƒ ‡• –‘ ƒ• –Š‡

„‹––‡”–ƒ•–‡‘ˆ–Š‡ƒ –‹˜‡‹‰”‡†‹‡–Ǥȏ͵Ȑ
MATERIALS AND METHODS
•‡Ž–ƒ‹˜‹”‹•ƒ†‹‹•–‡”‡†‘”ƒŽŽ›ǡ‹–‹•ƒƒ–‹˜‹”ƒŽ†”—‰
•‡Ž–ƒ‹˜‹” ™‡”‡ ”‡ ‡‹˜‡† ˆ”‘ ›†—• ƒ†‹Žƒ –†ǡ
ˆ‘” –Š‡ ƒƒ‰‡‡– ‘ˆ ‹ˆŽ—‡œƒ  ƒ†  ‹ˆ‡ –‹‘• ‹
Š‹Ž†”‡εͳ›‡ƒ”ƒ†ƒ†—Ž–•‘ˆƒŽŽƒ‰‡•Ǥ ȏͶȐ–ƒ†ƒ”††‘•‡‘ˆ Š‡†ƒ„ƒ†Ǥ  Ǧ͵Ͳǡ ”‘•’‘˜‹†‘‡ǡ ƒ‹–‘Žǡ ƒ‰‡•‹—
‘•‡Ž–ƒ‹˜‹” ‹ ƒ†—Ž–ǯ• ‹• ͹ͷ ‰ǡ ™Š‹Ž‡ Š‹Ž†”‡ Šƒ˜‡ —‹– •–‡ƒ”ƒ–‡ǡƒŽ ™ƒ•”‡ ‡‹˜‡†ˆ”‘Š”‹•ƒ‹Š‡‹ ƒŽǡ‘Žƒ’—”Ǥ
†‘•‡• –Šƒ– ƒ”‡ •‡Ž‡ –‡† ‘ –Š‡ „ƒ•‹• ‘ˆ „‘†› ™‡‹‰Š–Ǥ ”ƒŽ
ƒ’•—Ž‡ ȋ͵ͷǡ ͶͲ ƒ† ͹ͷ ‰Ȍ ƒ† •—•’‡•‹‘ ˆ‘”—Žƒ–‹‘• Calibration Curve of Oseltamivir
ƒ”‡ —””‡–Ž› ’”‘’–Ž› ‘ –Š‡ ƒ”‡–Ǥ • ˆƒ•– †‹••‘Ž˜‹‰  —”ƒ–‡Ž›™‡‹‰Š‡†ͳͲ‰‘ˆ†”—‰™ƒ•–”ƒ•ˆ‡””‡†–‘ͳͲŽ
–ƒ„Ž‡–• ƒŠ‘Ž†–Š‡†‘•‡—’–‘–Š‡ͷͲͲ‰™‡ ƒ•—‹–ƒ„Ž› ˜‘Ž—‡–”‹  ˆŽƒ• ƒ† †‹••‘Ž˜‡† ‹ ‡–Šƒ‘Žǡ –Š‹• ™ƒ•
ƒ†‹‹•–‡”͹ͷ‰‘ˆ†‘•‡ǤŠ‡‘—–Š†‹•‹–‡‰”ƒ–‹‰–ƒ„Ž‡– ‘•‹†‡”‡† ƒ• •–‘  •‘Ž—–‹‘Ǥ ”‘ •–‘  •‘Ž—–‹‘  ͲǤͳ Žǡ
‘ˆ‘•‡Ž–ƒ‹˜‹”™‹ŽŽ†‹•‹–‡‰”ƒ–‡”ƒ’‹†Ž›‹–Š‡’ƒ–‹‡–‘—–Š ͲǤʹŽǡͲǤ͵ŽǡͲǤͶŽǡͲǤͷŽǡ™‡”‡–ƒ‡ƒ†™ƒ•ƒ‡—’
™‹–Š‘—– ‡‡† ‘ˆ ™ƒ–‡” ‘” Š‡™‹‰ ƒ† ”‡Ž‡ƒ•‡† ‹–• †”—‰ –Š‡ ˜‘Ž—‡ –‘ ͳͲŽ ™‹–Š ‡–Šƒ‘Ž –‘ ‰‡– ”‡•’‡ –‹˜‡
‘–‡–• ‹•–ƒ–ƒ‡‘—•Ž›Ǥ ‘ –Š‹• †‘•ƒ‰‡ ˆ‘” ‹• ‘”‡ ‘ ‡–”ƒ–‹‘• ‘ˆ ȋͳͲǡ ʹͲǡ ͵Ͳǡ ͶͲ ƒ† ͷͲȌ Ɋ‰ȀŽǤ”‡’ƒ”‡†
‘ˆ‘”–ƒ„Ž‡ˆ‘”’ƒ‡†‹ƒ–”‹ ǡ‰‡”‹ƒ–”‹ ’ƒ–‹‡–ǤȏͶǦͷȐ •ƒ’Ž‡• ™‡”‡ ƒƒŽ›œ‡† „› —•‹‰ —Ž–”ƒ˜‹‘Ž‡– †‘—„Ž‡ „‡ƒ
•’‡ –”‘’Š‘–‘‡–‡”ƒ–ɉƒšʹͳͺǤ
ͳ ǤǤǤǤ ƒ†ƒŽǯ• ‘ŽŽ‡‰‡ ‘ˆ Šƒ”ƒ ›ǡ ‘Žƒ’—”ǦͶͳ͵ͲͲͶǡ ƒŠƒ”ƒ•Š–”ƒǡ
 
†‹ƒǤ Preparation of Oseltamivir Fast Dissolving Tablet
Ǧƒ‹Žǣ•Š”‹•Šƒ‹ŽǤ‰Š—”‰Š—”‡̷‰ƒ‹ŽǤ ‘ 1. Step-1 Solid Dispersion Technique-Solvent
ȗ‘””‡•’‘†‹‰ƒ—–Š‘” Evaporation Method

ʹ‘†‡” ‘ŽŽ‡‰‡ ‘ˆ Šƒ”ƒ ›ǡ ƒ—ƒƒ‰ƒ”ǡ ‹‰†‹ǡ —‡ǦͶͳͳͲͶͶǡ Š‡ •‘Ž‹† †‹•’‡”•‹‘• ‘ˆ ‘•‡Ž–ƒ‹˜‹” ™‡”‡ ’”‡’ƒ”‡† „›
ƒŠƒ”ƒ•Š–”ƒǡ †‹ƒǤ †‹••‘Ž˜‹‰ –Š‡ ‹š–—”‡ ‘ˆ ‘•‡Ž–ƒ‹˜‹” ƒ† –Š‡   ͵Ͳ ƒ–

˜‡–‹ƒ’‹†ǣŠƒ”‡ Š‘ŽǤʹͲʹͲǡ ••—‡͵ 1 ʹͲʹͲ’’–͵ͳͶͺʹ ̹ ˜‡–‹ ‘—”ƒŽ•ȋȌ–†


ȏ Ͳͻ͹͸Ǧ͵͹ͺ͵Ȑ —„Ž‹•Š‡†‘‡„ʹ͸ȀͲͶȀʹͲʹͲǡ™™™Ǥ‹˜‡–‹Ǥ‹
  

–Š‡ ™‡‹‰Š– ”ƒ–‹‘• ‘ˆ ͳǣͲǤͷ ™Ȁ™ǡ ™‹–Š –Š‡ Š‡Ž’ ‘ˆ ƒ „‘––‘ „αͲȀ
˜‘Ž—‡‘ˆ‹š–—”‡‘ˆ‡–Šƒ‘Žƒ†ƒ ‡–‘‡•‘Ž˜‡–•›•–‡ 

ȋͳǣͳ ˜Ȁ˜ȌǤ Š‡ •‘Ž˜‡– ™ƒ•”‡‘˜‡† „› ‡˜ƒ’‘”ƒ–‹‘ —†‡” Š‡”‡ǡ  ‹• ƒ•• ‘ˆ ’‘™†‡”ǡ Ͳ ‹• „—Ž ˜‘Ž—‡ ‘ˆ –Š‡
”‡†— ‡†’”‡••—”‡ƒ–͵͹‘Ǥ‘Ž‹†ƒ••‘„–ƒ‹‡†™ƒ••‹ŽŽ‡† ’‘™†‡”Ǥ
–Š‡͓•‹š–›ƒ†‡‡’‹˜ƒ ——†‡•‹ ƒ–‘”–‹ŽŽ—•‡Ǥ 
 b. Tapped Density (Dt)
2. Step-2 Preparation of Oseltamivir Fast Dissolving  —”ƒ–‡Ž› ™‡‹‰Š‡† “—ƒ–‹–› ‘ˆ ’‘™†‡” „Ž‡† ˆ”‘ ‡ƒ Š
Tablet ˆ‘”—Žƒƒˆ–‡”™‡‹‰Š‹‰–Š‡’‘™†‡”„Ž‡†™ƒ•–”ƒ•ˆ‡”‹–‘
ƒ•– †‹••‘Ž˜‹‰ –ƒ„Ž‡–• ‘ˆ ‘•‡Ž–ƒ‹˜‹” ™‡”‡ ’”‡’ƒ”‡† „› ƒ ‡ƒ•—”‹‰ ›Ž‹†‡”Ǥ ˆ–‡” –”ƒ•ˆ‡””‹‰ –Š‡ ‡ƒ•—”‹‰
†‹”‡ – ‘’”‡••‹‘ ‡–Š‘†Ǥ ŽŽ –Š‡ ‹‰”‡†‹‡–• ™‡”‡ ›Ž‹†‡”™ƒ•–ƒ’’‡†—–‹Ž‘ˆ—”–Š‡”„Ž‡†•™‡”‡ ƒŽ —Žƒ–‡†
’‘™†‡”‡† •‡’ƒ”ƒ–‡Ž› ƒ† ’ƒ••‡† –Š”‘—‰Š •‹‡˜‡ ‘Ǥ ͶͲ „›—•‹‰–Š‡ˆ‘ŽŽ‘™‹‰ˆ‘”—Žƒ

•‡’ƒ”ƒ–‡Ž›Ǥ Š‡ †”—‰ ƒ† ƒŽŽ ‡š ‹’‹‡– ™‡”‡ ‹š‡† „› –α–ȀǤ
ƒ††‹‰•ƒŽŽ’‘”–‹‘‘ˆ‡ƒ Šƒ–ƒ–‹‡ƒ†„Ž‡†‹‰‹––‘‰‡– 

ƒ —‹ˆ‘” ‹š–—”‡ ƒ† ‡’– ƒ•‹†‡Ǥ ˆ–‡” –Š‡ –Š‡ ‘–Š‡” Š‡”‡ǡ‹•ƒ••‘ˆ’‘™†‡”ǡ–‹•–ƒ’’‡†˜‘Ž—‡‘ˆ–Š‡
‹‰”‡†‹‡–• ™‡”‡ ‹š‡† ‹ ‰‡‘‡–”‹ ƒŽ ‘”†‡”ǡ ‹ ƒ ‹ˆŽƒ–‡ ’‘™†‡”Ǥ
’‘Ž›‡–Š›Ž‡‡ ’‘— Š ƒ‰‡•‹— •–‡ƒ”ƒ–‡ ƒ† –ƒŽ  ™‡”‡
ƒ††‡† Žƒ•– ƒ† ‹š‡† ˆ‘” ˆ—”–Š‡” –™‘ ‹—–‡• ƒ† –Š‡ c. Carr’s Index (%)
–ƒ„Ž‡–• ™‡”‡ ‘’”‡••‡† —•‹‰ ͺǦͳʹ  ‘˜ƒŽ •Šƒ’‡ Š‡ ƒ””ǯ• ‹†‡š ™ƒ• ƒŽ —Žƒ–‡† ƒ• ͳͲͲ –‹‡• –Š‡ ”ƒ–‹‘ ‘ˆ
’— Š‡• –‘ ‰‡– –ƒ„Ž‡–• ‘ˆ ͳͷͲ ‰ ™‡‹‰Š–Ǥ Š‡ –ƒ„Ž‡– –Š‡†‹ˆˆ‡”‡ ‡„‡–™‡‡–ƒ’’‡††‡•‹–›ƒ†„—Ž†‡•‹–›–‘
ˆ‘”—Žƒ–‹‘•’”‡’ƒ”‡†™‡”‡•Š‘™‹ƒ„Ž‡ʹǤ –Š‡ –ƒ’’‡† †‡•‹–›Ǥ Š‡ ƒ””ǯ• ‹†‡š ‘ˆ –Š‡ ’‘™†‡” ™ƒ•
 ƒŽ —Žƒ–‡†„›—•‹‰ˆ‘ŽŽ‘™‹‰ˆ‘”—ŽƒǤ
Evaluation of Fast Dissolving Tablets of Oseltamivir 
ƒ’’‡††‡•‹–› െ —Ž†‡•‹–›
1. Preformulation Studies ƒ””ǯ• †‡š ൌ ൈ ͳͲͲ
2. Compatibility Studies [8-10] ƒ’’‡††‡•‹–›
a. FTIR
 •–—†› ‘ˆ ’—”‡ †”—‰ ‘•‡Ž–ƒ‹˜‹” ƒ† ’Š›•‹ ƒŽ ‹š–—”‡ d. Hausner’s Ratio
™‡”‡ ’‡”ˆ‘”‡† –‘ ˆ‹† ‘—– ƒ› ’‘••‹„Ž‡ †”—‰Ǧ‡š ‹’‹‡– ƒ—•‡”ǯ• ”ƒ–‹‘ ‹• ƒ ‡ƒ•—”‡ ‘ˆ ˆ”ƒ –‹‘ƒŽ ˆ‘” ‡ ‡š‹•–‹‰ ‹
‹–‡”ƒ –‹‘ „› ” ’‡ŽŽ‡– ‡–Š‘† —•‹‰ ȋ  ’”‡•–‹‰‡ ʹͳ ‘˜‹‰ ’‘™†‡” ƒ••Ǥ ƒ—•‡”ǯ• ”ƒ–‹‘ ‹• –Š‡ ƒ‹ ”ƒ–‹‘ ‘ˆ
Š‹ƒ†œ—‘”’‘”ƒ–‹‘ǡ ƒ’ƒȌ•’‡ –”‘’Š‘–‘‡–‡”Ǥ –ƒ’’‡† †‡•‹–› –‘ „—Ž †‡•‹–›Ǥ – ‹• ƒŽ —Žƒ–‡ „› ˆ‘ŽŽ‘™‹‰
ˆ‘”—Žƒǣ

b. DSC —Ž‡•‹–›
Š‡ †‹ˆˆ‡”‡–‹ƒŽ  ƒ‹‰ ƒŽ‘”‹‡–”› ƒŽ›•‹• ™ƒ• ƒ—•‡”ǯ•ƒ–‹‘ ൌ 
’‡”ˆ‘”‡† „› —•‹‰  ͳȀ͹ͲͲȀʹͻ͸Ͳ  ͸Ͳǡ ƒ’’‡†‡•‹–›

‡––Ž‡” ‘Ž‡†‘ †‹ƒ ˜–Ǥ –†Ǥ ™‹–œ‡”Žƒ†ǡ —•‹‰ ”— ‹„Ž‡
e. Angle of Repose (Ɵ)
ƒŽ—‹—ͶͲρƒ–ǡͳͲιȀ‹Š‡ƒ–‹‰”ƒ–‡ǡ–Š‡–‡’‡”ƒ–—”‡
‰Ž‡ ‘ˆ ”‡’‘•‡ ™ƒ• ƒ‹Ž› †‡–‡”‹‡† „› —•‹‰ ˆ—‡Ž
”ƒ‰‡™ƒ•ʹͷι–‘͵ͲͲ鋐ƒ‹–”‘‰‡ƒ–‘•’Š‡”‡Ǥ
‡–Š‘†Ǥ Š‡ ƒ —”ƒ–‡ “—ƒ–‹–› ‘ˆ ’”‡’ƒ”‡† ’‘™†‡” „Ž‡†
™ƒ• –”ƒ•ˆ‡””‡† –Š”‘—‰Š ƒ ˆ—‡Ž –Šƒ– ƒ „‡ ”ƒ‹•‡†
c. XRD
˜‡”–‹ ƒŽŽ› —–‹Ž ƒ ƒš‹— ‘‡ Š‡‹‰Š– ™ƒ• ‘„–ƒ‹‡†Ǥ Š‡
Š›•‹ ƒŽ ƒ–—”‡• ‘ˆ †”—‰ ƒ† ‘’–‹‹œ‡† ˆ‘”—Žƒ–‹‘ ™‡”‡
”ƒ†‹—•‘ˆƒ‰‰”‡‰ƒ–‡™ƒ•‡ƒ•—”‡†ƒ†ƒ‰Ž‡‘ˆ”‡’‘•‡™ƒ•
ƒƒŽ›œ‡† „› Ǧ”ƒ› †‹ˆˆ”ƒ –‹‘ ȋȌǤ  ’ƒ––‡”• ‘ˆ –Š‡
ƒŽ —Žƒ–‡†„›—•‹‰ˆ‘ŽŽ‘™‹‰ˆ‘”—Žƒǣ
’‘™†‡”‡† •ƒ’Ž‡• ‘ˆ –Š‡ †”—‰ ƒ† –Š‡ ‘’–‹‹•‡† 
ˆ‘”—Žƒ–‹‘ ”‡ ‘”†‡† —•‹‰ Ǧ”ƒ› ’‘™†‡” †‹ˆˆ”ƒ –‘‡–‡” ፽α–ƒǦͳȋŠȀ”Ȍ
™‹–Šƒ ‘’’‡”–—„‡ƒ‘†‡‘˜‡”–Š‡‹–‡”˜ƒŽͲǦ͸ͲιʹɅΫͳǤŠ‡ 
‘’‡”ƒ–‹‘ƒŽ’ƒ”ƒ‡–‡”•™‡”‡ƒ•ˆ‘ŽŽ‘™•ǣ ‡‡”ƒ–‘”–‡•‹‘ Š‡”‡ǡ፽ა‰Ž‡‘ˆ”‡’‘•‡Ǥ
ȋ˜‘Ž–ƒ‰‡Ȍ ‘ˆ Ͷͷ Ǣ ‰‡‡”ƒ–‘” —””‡– ‘ˆ ͶͲ Ǣ • ƒ •–‡’ 
–‹‡‘ˆͻȀ•ƒ†• ƒ•–‡’•‹œ‡‘ˆͲǤͲͲͺιȋʹɅȌǤ 4. Evaluation of Tablets [16-17]
 a. Weight Variation
3. Evaluation of Blends ™‡–› –ƒ„Ž‡–• ™‡”‡ •‡Ž‡ –‡† ƒ† ™‡‹‰Š‡† ‘ †‹‰‹–ƒŽ
Š‡ ’”‡’ƒ”‡† ’‘™†‡” „Ž‡†• ™‡”‡ ‡˜ƒŽ—ƒ–‡† ˆ‘” „—Ž ™‡‹‰Š‹‰ „ƒŽƒ ‡ ȋŠƒ—•ǡ Ȍ ƒ† ƒ˜‡”ƒ‰‡ ™‡‹‰Š– ™ƒ•
†‡•‹–›ǡ –ƒ’’‡† †‡•‹–›ǡ ƒ””ǯ• ‹†‡šǡ ƒ—•‡”ǯ• ”ƒ–‹‘ ƒ† †‡–‡”‹‡†ǤŠ‡‹†‹˜‹†—ƒŽ–ƒ„Ž‡–•™‡”‡™‡‹‰Š‡†ƒ†–Š‡
ƒ‰Ž‡‘ˆ”‡’‘•‡ǤȏͳͳǦͳͷȐ ‹†‹˜‹†—ƒŽ™‡‹‰Š–™ƒ• ‘’ƒ”‡†™‹–Šƒƒ˜‡”ƒ‰‡™‡‹‰Š–Ǥ ȏͻȐ
Š‡–ƒ†ƒ”†Ž‹‹–ƒ••Š‘™‹„‡Ž‘™ǣ
a. Bulk Density (Db) 
 —”ƒ–‡Ž› ™‡‹‰Š‡† “—ƒ–‹–› ‘ˆ ’‘™†‡” „Ž‡† ˆ”‘ ‡ƒ Š ˜‡”ƒ‰‡™–Ǥ‘ˆ–ƒ„Ž‡– ƒš‹—‡” Ǥ‹ˆˆ‡”‡ ‡
ˆ‘”—Žƒƒˆ–‡”™‡‹‰Š‹‰–Š‡’‘™†‡”„Ž‡†™ƒ•–”ƒ•ˆ‡”‹–‘ ȋ‰Ȍ ŽŽ‘™
ƒ‡ƒ•—”‹‰ ›Ž‹†‡”ǤŠ‡˜‘Ž—‡‘ —’‹‡†„›–Š‡’‘™†‡” ͺͲ‘”Ž‡•• άͳͲΨ
„Ž‡†™ƒ•‡ƒ•—”‡†™Š‹ Š‰ƒ˜‡–Š‡„—Ž˜‘Ž—‡ǤŠ‡„—Ž ”‘ͺͲ–‘ʹͷͲ ά͹ǤͷΨ
†‡•‹–› ‘ˆ ’‘™†‡” „Ž‡†• ™ƒ• ƒŽ —Žƒ–‡ „› —•‹‰ –Š‡ εʹͷͲ άͷΨ
ˆ‘ŽŽ‘™‹‰ˆ‘”—ŽƒǤ ‹‹–ˆ‘”–ƒ„Ž‡–™‡‹‰Š–˜ƒ”‹ƒ–‹‘–‡•–

˜‡–‹ƒ’‹†ǣŠƒ”‡ Š‘ŽǤʹͲʹͲǡ ••—‡͵ 2 ʹͲʹͲ’’–͵ͳͶͺʹ ̹ ˜‡–‹ ‘—”ƒŽ•ȋȌ–†


ȏ Ͳͻ͹͸Ǧ͵͹ͺ͵Ȑ —„Ž‹•Š‡†‘‡„ʹ͸ȀͲͶȀʹͲʹͲǡ™™™Ǥ‹˜‡–‹Ǥ‹
  

Table 1: For Organoleptic Property of API (Oseltamivir)



Organoleptic Property of API
Properties Result
‘Ž‘—” Š‹–‡ǡ ”›•–ƒŽŽ‹‡’‘™†‡”
‡•– ”ƒ –‹ ƒŽŽ›‡•–Ž‡••
†‘—” †‘—”Ž‡••

Table 2: Standard Calibration Graph Values of Oseltamivir in Methanol

Concentration (μg/ml) Absorbance


Ͳ Ͳ
ͳͲ ͲǤͲͶ
ʹͲ ͲǤͲͻ͵
͵Ͳ ͲǤͳͶʹ
ͶͲ ͲǤͳͻʹ
ͷͲ ͲǤʹͷʹ



b. Friability g. Wetting Time


”‹ƒ„‹Ž‹–› ‘ˆ –Š‡ –ƒ„Ž‡– ƒ „‡ †‡–‡”‹‡ ‹ Žƒ„‘”ƒ–‘”› „› ‡–”‹’Žƒ–‡ ‘–ƒ‹‹‰͸Ž‘ˆ†‹•–‹ŽŽ‡†™ƒ–‡”™ƒ•–ƒ‡Ǥ
‘ Š‡ ”‹ƒ„‹Žƒ–‘”Ǥ Š‹• ‘•‹•– ‘ˆ ƒ ’Žƒ•–‹  Šƒ„‡” –Šƒ– –ƒ„Ž‡– ‘–ƒ‹‹‰ ƒ •ƒŽŽ “—ƒ–‹–› ‘ˆ ƒƒ”ƒ–Š ‘Ž‘—” ™ƒ•
”‡˜‘Ž˜‡•ƒ–ʹͷ”’ǡ†”‘’’‹‰–Š‡–ƒ„Ž‡–•–Š”‘—‰Šƒ†‹•–ƒ ‡ ’Žƒ ‡† ‘ ‹–Ǥ ‹‡ ”‡“—‹”‡† ˆ‘” –Š‡ —’’‡” •—”ˆƒ ‡ ‘ˆ –Š‡
‘ˆ•‹š‹ Š‡•‹–Š‡ˆ”‹ƒ„‹Žƒ–‘”ǡ™Š‹ Š‹•–Š‡‘’‡”ƒ–‡ˆ‘”ͳͲͲ –ƒ„Ž‡––‘„‡ ‘‡ ‘’Ž‡–‡†™ƒ•‘–‡†Ǥ
”‡˜‘Ž—–‹‘Ǥ ˆ–‡” ‘’Ž‡–‡ –Š‡•‡ ’”‘ ‡•• –ƒ„Ž‡–• ™‡”‡
†—•–‡†ƒ†”‡™‡‹‰Š‡†Ǥ h. In-Vitro Dissolution Data

‹••‘Ž—–‹‘ –‡•– ™ƒ• †‡–‡”‹‡† „› —•‹‰  –›’‡ 
”‹ƒ„‹Ž‹–›αͳǦʹȀͳέͳͲͲ
 ȋ’ƒ††Ž‡Ȍƒ’’ƒ”ƒ–—•ǤŠ‡’ƒ††Ž‡™ƒ•”‘–ƒ–‡†ƒ–ͷͲ”’Ǥ’ 
Š‡”‡ǡͳα ‹–‹ƒŽ™‡‹‰Š–ƒ†ʹαˆ‹ƒŽ™‡‹‰Š–Ǥ ͸ǤͺŠ‘•’Šƒ–‡„—ˆˆ‡”™ƒ•—•‡†ƒ•†‹••‘Ž—–‹‘‡†‹—ȋͻͲͲ
ŽȌ ƒ† ™ƒ• ƒ‹–ƒ‹‡† ƒ– ͵͹άͳ‘Ǥ ƒ’Ž‡• ‘ˆ ͷ Ž ™‡”‡
c. Thickness ™‹–Š†”ƒ™ ƒ– ’”‡†‡–‡”‹‡† ‹–‡”˜ƒŽ• ȋͷǡ ͳͲǡ ͳͷǡ ʹͲǡ ʹͷ
Š‹ ‡••‘ˆ–ƒ„Ž‡–•™ƒ•†‡–‡”‹‡†—•‹‰˜‡”‹‡” ƒŽŽ‹’‡” ƒ†͵ͲȌǡˆ‹Ž–‡”‡†ƒ†”‡’Žƒ ‡†™‹–ŠͷŽ‘ˆˆ”‡•Š†‹••‘Ž—–‹‘
ȋ †‹ƒ ƒŽŽ‹’‡” †—•–”‹‡•ǡ „ƒŽƒǡ †‹ƒȌǤ Š”‡‡ –ƒ„Ž‡–• ‡†‹—Ǥ
ˆ”‘ ‡ƒ Š „ƒ– Š ™‡”‡ —•‡† ƒ† ƒ ƒ˜‡”ƒ‰‡ ˜ƒŽ—‡ ™ƒ• Š‡ ‘ŽŽ‡ –‡† •ƒ’Ž‡• ™‡”‡ •—‹–ƒ„Ž› †‹Ž—–‡† ™‹–Š
ƒŽ —Žƒ–‡†Ǥ †‹••‘Ž—–‹‘ ˆŽ—‹†ǡ ™Š‡”‡˜‡” ‡ ‡••ƒ”› ƒ† ™‡”‡ ƒƒŽ›œ‡†
ˆ‘” –Š‡ †”—‰ ƒ– ʹͳͺ  „› —•‹‰ —Ž–”ƒ˜‹‘Ž‡– †‘—„Ž‡ „‡ƒ
d. Hardness •’‡ –”‘’Š‘–‘‡–‡”Ǥ
 –Š‹• –‡ Š‹“—‡ –ƒ„Ž‡– ”—•Š‹‰ •–”‡‰–Š ™ƒ• ‡ƒ•—”‡†
—•‹‰ ƒ ‘•ƒ–‘ Šƒ”†‡•• –‡•–‡”Ǥ Š‡•‡ Šƒ”†‡•• RESULTS AND DISCUSSION
–‡ Š‹“—‡—•‹‰–Š”‡‡–ƒ„Ž‡–•ˆ”‘‡ƒ Šˆ‘”—Žƒ–‹‘„ƒ– Š Calibration of Oseltamivir
™‡”‡–‡•–‡†”ƒ†‘Ž›ƒ†–Š‡ƒ˜‡”ƒ‰‡”‡ƒ†‹‰™ƒ•‘–‡†Ǥ Š‡ɉƒš‘ˆ‘•‡Ž–ƒ‹˜‹” ™ƒ•†‡–‡”‹‡†„›• ƒ‹‰–Š‡
Š‡Šƒ”†‡••‹•‡ƒ•—”‡†‹‰Ȁ ʹǤ ͳͲ ρ‰ȀŽ •‘Ž—–‹‘ ‘ˆ †”—‰ —•‹‰ Ǧ’‡ –”‘’Š‘–‘‡–‡”
ƒ† ™ƒ• ˆ‘—† –‘ „‡ ʹͳͺ Ǥ Š‡ ƒ„•‘”„ƒ ‡ ‘ˆ –Š‡
e. Content Uniformity Test •‘Ž—–‹‘ ͳͲ –‘ ͷͲ ρ‰ȀŽ ™ƒ• ‡ƒ•—”‡† ‹ Ǧ
‡ –ƒ„Ž‡–• ȋͳͷͲ‰Ȍ ™‡”‡ ’‘™†‡”‡† ‹ ‘”–ƒ” ’‡•–Ž‡ ƒ† ’‡ –”‘’Š‘–‘‡–‡” ƒ– ʹͳͺ  ȋƒ„Ž‡ ͳȌǤ Š‡ Ž‹‡ƒ”
–Š‡ „Ž‡† ‡“—‹˜ƒŽ‡– –‘ ʹ ‰ ‘ˆ ‘•‡Ž–ƒ‹˜‹” ™ƒ• ™‡‹‰Š‡† ‘””‡Žƒ–‹‘ ™ƒ• ˆ‘—† –‘ „‡ ͲǤͻͻ͹Ͷ ȋŠ ͸Ǥͺ Š‘•’Šƒ–‡
ƒ† †‹••‘Ž˜‡† ‹ ͳͲͲ Ž ‘ˆ ͸Ǥͺ ’  ’Š‘•’Šƒ–‡ „—ˆˆ‡” „—ˆˆ‡”Ȍȋ ‹‰—”‡ͳȌǤ
•‘Ž—–‹‘•Ǥˆ–‡”’”‡’ƒ”‹‰–Š‡•‡•‘Ž—–‹‘™ƒ••‘‹ ƒ–‡†ƒ†
ˆ‹Ž–‡”‡†–Š”‘—‰Š™Šƒ–ƒˆ‹Ž–‡”’ƒ’‡”ƒ†•—‹–ƒ„Ž›†‹Ž—–‡† Pre-formulation Evaluations
™‹–Š ͸Ǥͺ’  ’Š‘•’Šƒ–‡ „—ˆˆ‡” ƒ† –Š‡ †”—‰ ‘–‡– ™ƒ• Ǧ  •’‡ –”— ‘ˆ ’—”‡ †”—‰ ‘•‡Ž–ƒ‹˜‹” ƒ† ’Š›•‹ ƒŽ
ƒƒŽ›œ‡† „› —•‹‰ †‘—„Ž‡ „‡ƒ  •’‡ –”‘’Š‘–‘‡–‡” ‹š–—”‡ ‘ˆ †”—‰ ƒ† •—’‡”†‹•‹–‡‰”ƒ–• ”‘•’‘˜‹†‘‡ǡ
ȋǦͳͺͲͲ Š‹ƒ†œ—Ȍ ƒ– ʹͳͺǡ ”‡•’‡ –‹˜‡Ž›Ǥ ƒ Š •ƒ’Ž‡ šƒ–Šƒ ‰— ƒ† ‘„‹ƒ–‹‘ ‘ˆ ”‘•’‘˜‹†‘‡ Ϊ šƒ–Šƒ
™ƒ•ƒƒŽ›œ‡†‹–”‹’Ž‹ ƒ–‡Ǥ ‰— ™‡”‡ •–—†‹‡† ƒ† •’‡ –”— ‹• •Š‘™ ‹ ‹‰—”‡ ʹǦͷǤ
”—‰ ’‘Ž›‡” ‘’ƒ–‹„‹Ž‹–› •–—†‹‡• ƒ”‡ ˜‡”› ‹’‘”–ƒ– ‹
f. In-Vitro Disintegration Time ‘”†‡” –‘ ‘ˆ‹” –Š‡ †”—‰ •–”— –—”‡ǡ ‹–• ƒ –‹˜‹–› ƒ† ‹–•
Š‡ –‡•– ™ƒ• ƒ””‹‡† ‘—– ‘ ͸ –ƒ„Ž‡–• —•‹‰ †‹‰‹–ƒŽ –ƒ„Ž‡– †‡‰”ƒ†ƒ–‹‘ ”ƒ–‡ ƒ† ”‡Ž‡ƒ•‡ ’ƒ––‡” ™‹–Š ˜ƒ”‹‘—•
†‹•‹–‡‰”ƒ–‹‘ –‡•–‡” ȋ‡‡‰‘ǡ †‹ƒȌǤ ‹•–‹ŽŽ‡† ™ƒ–‡” ƒ– ’‘Ž›‡”‹  •—„•–ƒ ‡• —•‡† ‹ –Š‡ ˆ‘”—Žƒ–‹‘Ǥ  –Š‹•
͵͹ιάʹ陃•—•‡†ƒ•ƒ†‹•‹–‡‰”ƒ–‹‘‡†‹ƒƒ†–Š‡–‹‡ ’”‡•‡– •–—†›ǡ ‹– ™ƒ• ƒ‹Ž› ‘„•‡”˜‡† –Šƒ–ǡ –Š‡”‡ ™‡”‡ ‘
–ƒ‡ ˆ‘” ‘’Ž‡–‡ †‹•‹–‡‰”ƒ–‹‘ ‘ˆ –Š‡ –ƒ„Ž‡– ™‹–Š ‘ ƒŒ‘” •Š‹ˆ–• ‹ ‹–• ‹†‹˜‹†—ƒŽ ƒ‹ ’‡ƒ•Ǥ ‘ –Š‹• ‹†‹ ƒ–‡•
’ƒŽ’ƒ„Ž‡ƒ••”‡ƒ‹‹‰‹–Š‡ƒ’’ƒ”ƒ–—•™ƒ•‡ƒ•—”‡†‹ –Šƒ– –Š‡”‡ ™ƒ• ‘ ‘’ƒ–‹„‹Ž‹–› ‹••—‡• ‘ˆ †”—‰ ™‹–Š
•‡ ‘†•Ǥ ˆ‘”—Žƒ–‹‘’‘Ž›‡”•—•‡†Ǥ

˜‡–‹ƒ’‹†ǣŠƒ”‡ Š‘ŽǤʹͲʹͲǡ ••—‡͵ 3 ʹͲʹͲ’’–͵ͳͶͺʹ ̹ ˜‡–‹ ‘—”ƒŽ•ȋȌ–†


ȏ Ͳͻ͹͸Ǧ͵͹ͺ͵Ȑ —„Ž‹•Š‡†‘‡„ʹ͸ȀͲͶȀʹͲʹͲǡ™™™Ǥ‹˜‡–‹Ǥ‹
  


Figure 1:ƒŽ‹„”ƒ–‹‘ —”˜‡‘ˆ‘•‡Ž–ƒ‹˜‹”

90
3349.84

3157.40

80
2875.74
2937.79

1444.59
1330.94
70
%Transmittance

1621.19
2965.95

1463.44
1373.67
60

1204.49

786.70
1660.59

1548.74

603.35
50

1721.98

1242.881260.15

552 19
1166.81 1188.74

654.79
851.66
1025.21
40

1124.91
1290.46

677.12
950.64
873.82
1067.50
30

730.09
967.01
20
4000 3500 3000 2500 2000 1500 1000
Wavenumbers (cm-1) 
Figure 2:  •’‡ –”—‘ˆ‘•‡Ž–ƒ‹˜‹”


Figure 3:  •’‡ –”—‘ˆ‘•‡Ž–ƒ‹˜‹”Ϊ ”‘•’‘˜‹†‘‡

Figure 4:  •’‡ –”—‘ˆ‘•‡Ž–ƒ‹˜‹”Ϊšƒ–Šƒ‰—

90
3349.33

2850.35
3281.46

1722.08
2916.56

80
1375.17
3391.07

1463.03
%Transmittance

1652.02

1125.82
1421.61
1544.54

70
1261.06 1277.53

784.17
952.82
1208.28

730.20
863.76

60
1070.16

970.36
878.12

579.92 629.53
1017.83

50
552 91
664.70

567.36

40

4000 3500 3000 2500 2000 1500 1000


Wavenumbers (cm-1)

Figure 5:  •’‡ –”—‘ˆ‘•‡Ž–ƒ‹˜‹”Ϊ ”‘•’‘˜‹†‘‡Ϊšƒ–Šƒ‰—

˜‡–‹ƒ’‹†ǣŠƒ”‡ Š‘ŽǤʹͲʹͲǡ ••—‡͵ 4 ʹͲʹͲ’’–͵ͳͶͺʹ ̹ ˜‡–‹ ‘—”ƒŽ•ȋȌ–†


ȏ Ͳͻ͹͸Ǧ͵͹ͺ͵Ȑ —„Ž‹•Š‡†‘‡„ʹ͸ȀͲͶȀʹͲʹͲǡ™™™Ǥ‹˜‡–‹Ǥ‹
  


Figure 6:Š‡”‘‰”ƒ‘ˆ‘•‡Ž–ƒ‹˜‹”

Figure 7:Š‡”‘‰”ƒ‘ˆ‘•‡Ž–ƒ‹˜‹”Ϊ ”‘•’‘˜‹†‘‡

Figure 8:Š‡”‘‰”ƒ‘ˆ‘•‡Ž–ƒ‹˜‹”Ϊšƒ–Šƒ‰—

Figure 9:Š‡”‘‰”ƒ‘ˆ‘•‡Ž–ƒ‹˜‹”Ϊ ”‘•’‘˜‹†‘‡Ϊšƒ–Šƒ‰—

DSC ƒ‰”‡‡‡–™‹–Š–Š‡‡†‘–Š‡”‹ ’‡ƒ‘ˆ–Š‡–Š‡”‘‰”ƒȌǤ


Š‡ –Š‡”ƒŽ „‡Šƒ˜‹‘—” ‘ˆ ‘•‡Ž–ƒ‹˜‹” ƒ• ™‡ŽŽ ƒ• •‘Ž‹† Š‡–Š‡”‘‰”ƒ‘ˆ’—”‡†”—‰ ‘’ƒ –•Š‘™‹ ‹‰—”‡͹Ǧͻ
†‹•’‡”•‹‘ ‹ ‘”’‘”ƒ–‡† ‘’–‹‹œ‡† „ƒ– Š ˆ‘”—Žƒ–‹‘ ƒ• ”‡–ƒ‹• –Š‡ ‘•‡– –‡’‡”ƒ–—”‡ ‹ –Š‡ ‡†‘–Š‡” ’‡ƒ ƒ–
•Š‘™‹ ‹‰—”‡͸ǦͻǤŠ‘™‡†ƒ‹‹–‹ƒŽˆŽƒ–’”‘ˆ‹Ž‡ˆ‘ŽŽ‘™‡† ͳ͸ͺιǤ Š‡”‡ ‹• ‘ •Š‹ˆ– ‹ –Š‡ ‡†‘–Š‡”‹  ’‡ƒ ‘ˆ
„› ƒ •Šƒ”’ Šƒ”ƒ –‡”‹•–‹  ‡†‘–Š‡”‹  ’‡ƒ ™‹–Š ƒ ‘•‡– ‘•‡Ž–ƒ‹˜‹”‹†‹ ƒ–‹‰–Šƒ––Š‡”‡‹•‘’Š›•‹ ƒŽ‘” Š‡‹ ƒŽ
ƒ– ʹͲͺι ȋŠ‡ ‘„•‡”˜‡† ‡Ž–‹‰ ’‘‹– ‘ˆ –Š‡ †”—‰ ™ƒ• ‹ Šƒ‰‡Ǥ

˜‡–‹ƒ’‹†ǣŠƒ”‡ Š‘ŽǤʹͲʹͲǡ ••—‡͵ 5 ʹͲʹͲ’’–͵ͳͶͺʹ ̹ ˜‡–‹ ‘—”ƒŽ•ȋȌ–†


ȏ Ͳͻ͹͸Ǧ͵͹ͺ͵Ȑ —„Ž‹•Š‡†‘‡„ʹ͸ȀͲͶȀʹͲʹͲǡ™™™Ǥ‹˜‡–‹Ǥ‹
  


Figure 10: ‘ˆ‘•‡Ž–ƒ‹˜‹”



Figure 11: ‘ˆ‘•‡Ž–ƒ‹˜‹”Ϊ ”‘•’‘˜‹†‘‡


Figure 12: ‘ˆ‘•‡Ž–ƒ‹˜‹”Ϊšƒ–Šƒ‰—


Figure 13: ‘ˆ‘•‡Ž–ƒ‹˜‹”Ϊšƒ–ŠƒΪ ”‘•’‘˜‹†‘‡

XRD ȋ‘•‡Ž–ƒ‹˜‹”Ϊƒ–Šƒ‰—Ȍƒ†‘’–‹‹œ‡†ˆ‘”—Žƒ–‹‘ ͹
Š‡ šǦ”ƒ› †‹ˆˆ”ƒ –‹‘ ’ƒ––‡” ‘ˆ •‡Ž–ƒ‹˜‹” •Š‘™ •Šƒ”’ •Š‘™ –Šƒ– –Š‡ Š‡‹‰Š– ’‡ƒ ƒ– ͳ͹ǤͲͶ͸ •Š‘™• •Šƒ”’ ’‡ƒ
’‡ƒǡ ƒ– ͳ͸ǤͻͺͲ ’• ƒ† Ž‡•• †‹ˆˆ—•‡† ’‡ƒ• ƒ– ͵Ǥ͵ͺʹ ƒ† Ž‡•• †‹ˆˆ—•‡† ’‡ƒ ƒ– ͵ǤͲʹͳ ƒ• •Š‘™ ‹ ‹‰—”‡ ͳʹǤ –
‹†‹ ƒ–‹‰–Š‡ ”›•–ƒŽŽ‹‡ƒ–—”‡‘ˆ†”—‰ƒ••Š‘™‹ ‹‰—”‡ •Š‘™‡† –Šƒ– –Š‡ †‹ˆˆ”ƒ –‹‘ ’‡ƒ• ƒ– ʹ፽ †‡‰”‡‡ ͷǤͳͺͲ –‘
ͳͲǤ Š‡ ‘„‹ƒ–‹‘ ‘ˆ †”—‰ ȋ‘•‡Ž–ƒ‹˜‹” Ϊ ”‘•’‘˜‹†‘‡Ȍ ʹͻǤͷͶͲǤ Š‡ ‘„‹ƒ–‹‘ ‘ˆ †”—‰ ȋ•‡Ž–ƒ‹˜‹” Ϊ
ƒ† ‘’–‹‹œ‡† ˆ‘”—Žƒ–‹‘ Ͷ •Š‘™ –Šƒ– –Š‡ Š‡‹‰Š– ’‡ƒ ”‘•’‘˜‹†‘‡ Ϊ šƒ–Šƒ ‰—Ȍ ƒ† ‘’–‹‹œ‡† ˆ‘”—Žƒ–‹‘
ƒ–ͳ͹ǤͲͶ͸•Š‘™••Šƒ”’’‡ƒƒ†Ž‡••†‹ˆˆ—•‡†’‡ƒƒ–ʹǤͲͷͲ ͳʹ•Š‘™–Šƒ––Š‡Š‡‹‰Š–’‡ƒƒ–͸Ǥ͹Ͳ͹•Š‘™••Šƒ”’’‡ƒ
ƒ••Š‘™‹ ‹‰—”‡ͳͳǤ –•Š‘™‡†–Šƒ––Š‡†‹ˆˆ”ƒ –‹‘’‡ƒ• ƒ† Ž‡•• †‹ˆˆ—•‡† ’‡ƒ ƒ– ʹǤͶͺͳ ƒ• •Š‘™ ‹ ‹‰—”‡ ͳ͵Ǥ –
ƒ– ʹ፽ †‡‰”‡‡ ͷǤͳͺͲ –‘ ͶͶǤͳͷͲǤ Š‡ ‘„‹ƒ–‹‘ ‘ˆ †”—‰ •Š‘™‡† –Šƒ– –Š‡ †‹ˆˆ”ƒ –‹‘ ’‡ƒ• ƒ– ʹ፽ †‡‰”‡‡ ͳ͵ǤͳͻͲ –‘

˜‡–‹ƒ’‹†ǣŠƒ”‡ Š‘ŽǤʹͲʹͲǡ ••—‡͵ 6 ʹͲʹͲ’’–͵ͳͶͺʹ ̹ ˜‡–‹ ‘—”ƒŽ•ȋȌ–†


ȏ Ͳͻ͹͸Ǧ͵͹ͺ͵Ȑ —„Ž‹•Š‡†‘‡„ʹ͸ȀͲͶȀʹͲʹͲǡ™™™Ǥ‹˜‡–‹Ǥ‹
  

Table 3: Pre Compression Studies of Powder Blend

Formulation Angle of Bulk Density Tapped Density Carrs Index Hausners


Code Repose (gm/ml) (gm/cc) (%) Ratio
ͳ ʹͶǤͶ͸ ͲǤ͵ͳ ͲǤ͵ͷ ͳͳǤͶʹ ͳǤͳͳ
ʹ ʹͳǤͺͲ ͲǤ͵ʹ ͲǤ͵͸ ͳͳǤͳͳ ͳǤͳʹ
͵ ʹʹǤ͸ͳ ͲǤ͵Ͳ ͲǤ͵Ͷ ͳͳǤ͹͸ ͳǤͳ͵
Ͷ ʹͶǤͶͶ ͲǤʹͻ ͲǤ͵͵ ͳʹǤͳʹ ͳǤͳ͵
ͷ ʹͶǤͶͶ ͲǤ͵ͳ ͲǤ͵͸ ͳ͵Ǥͺͺ ͳǤͳ͸
͸ ʹͷǤͶ ͲǤ͵ʹ ͲǤ͵ͺ ͳͷǤ͹ͺ ͳǤͳͺ
͹ ʹͷǤͶ͸ ͲǤ͵ ͲǤ͵Ͷ ͳʹǤ͹ͻ ͳǤͳͶ
ͺ ʹ͵ǤͶͻ ͲǤ͵ ͲǤ͵͵ ͻǤͲͻ ͳǤͳ
ͻ ʹʹǤ͵Ͳ ͲǤʹͻ ͲǤ͵ʹ ͻǤ͵͹ͷ ͳǤͳͲ
ͳͲ ʹͶǤʹͲ ͲǤʹͻ ͲǤ͵͵ ͳʹǤͳʹ ͳǤͳ͵
ͳͳ ʹͶǤ͹͹ ͲǤ͵ ͲǤ͵Ͷ ͳͳǤ͹͸ ͳǤͳ͵
ͳʹ ʹ͵Ǥͻͳ ͲǤʹͻ ͲǤ͵Ͷ ͳͶǤ͹Ͳ ͳǤͳ͹



͵͸ǤͳͺͲǤ ‘™‡˜‡” –Š‡ šǦ”ƒ› †‹ˆˆ”ƒ –‹‘ ’ƒ––‡” ‘ˆ ’—”‡ ˆ‘”—Žƒ–‹‘•Ǥ Š‡ ˜ƒŽ—‡ „‡Ž‘™ ʹͳΨ •Š‘™ ‰‘‘†
‘•‡Ž–ƒ‹˜‹” ƒ† ‘’–‹‹œ‡† „ƒ– Š Ͷǡ ͹ ƒ† ͳʹ ™‡”‡ ‘’”‡••‹„‹Ž‹–›Ǥ Š‡ ‘’”‡••‹„‹Ž‹–› ‹†‡š ‘ˆ ƒŽŽ –Š‡
•‹’Ž› ƒ •—’‡”‹’‘•‹–‹‘ ‘ˆ ‡ƒ Š ‘’‘‡– ™‹–Š ”‡•’‡ – ˆ‘”—Žƒ–‹‘• ”ƒ‰‡• ˆ”‘ ͻǤͲͻ –‘ ͳͷǤ͹ͺǤ Š‡ ”‡•—Ž–•
–‘–Š‡’‡ƒ•‘ˆ‘•‡Ž–ƒ‹˜‹”Ǥ‘”‡‘˜‡”ǡ–Š‡”‡Žƒ–‹˜‡‹–‡•‹–› ‹†‹ ƒ–‡–Šƒ––Š‡’‘™†‡”„Ž‡†‘ˆƒŽŽˆ‘”—Žƒ–‹‘•’‘••‡••
ƒ†ʹ፽ƒ‰Ž‡‘ˆ–Š‡•‡’‡ƒ•”‡ƒ‹— Šƒ‰‡†ǤŠ—•ǡ–Š‡”‡ ‰‘‘† ˆŽ‘™ ’”‘’‡”–‹‡•Ǥ Š‡ ”‡•—Ž–• ‘ˆ ƒŽŽ ˆ‘”—Žƒ–‹‘• ƒ”‡
™ƒ• ‘ ƒ‘”’Š‹œƒ–‹‘ ‘ˆ ‘•‡Ž–ƒ‹˜‹” ™Š‹ Š •–‹ŽŽ ”‡ƒ‹ ‹ •—ƒ”‹•‡†‹ƒ„Ž‡͵Ǥ
‘”‹‰‹ƒŽ ”›•–ƒŽŽ‹‡ˆ‘”Ǥ 
 5. Hausner’s Ratio
Precompression Evaluations for the Powder Blend  Š‡ ƒ—•‡”ǯ•”ƒ–‹‘‹•ƒ‘–Š‡”’ƒ”ƒ‡–‡”–‘‘„–ƒ‹‡†ˆŽ‘™
”‡ ‘’”‡••‹‘‡˜ƒŽ—ƒ–‹‘•™‡”‡†‘‡–‘‡•—”‡–Š‡ˆŽ‘™ ’”‘’‡”–‹‡•ǤŠ‡˜ƒŽ—‡‘ˆ”ƒ–‹‘„‡Ž‘™ͳǤʹͷ‹†‹ ƒ–‡‰‘‘†ˆŽ‘™
’”‘’‡”–‹‡•‘ˆ–Š‡’‘™†‡”„Ž‡†Ǥ ‘‘†ˆŽ‘™’”‘’‡”–‹‡•‘ˆ–Š‡ ’”‘’‡”–›Ǥ Š‡ ƒ—•‡”ǯ• ”ƒ–‹‘ ˆ‘” ’‘™†‡” „Ž‡†• ‘ˆ ƒŽŽ ͳʹ
’‘™†‡” „Ž‡† ™‹ŽŽ ›‹‡Ž† –Š‡ –ƒ„Ž‡–• ‘ˆ †‡•‹”‡† “—ƒŽ‹–› ƒ† ˆ‘”—Žƒ–‹‘• ”ƒ‰‡• ˆ”‘ ͳǤͳͲ –‘ ͳǤͳͺǤ – ™ƒ• ‘„•‡”˜‡†
‡ƒ•‡ –Š‡ –ƒ„Ž‡–‹‰ ’”‘ ‡••Ǥ ‘ ‹– ™ƒ• ƒ†ƒ–‘”› –‘ ƒ••‡•• ˆ”‘–Š‡”‡•—Ž–•–Šƒ––Š‡’‘™†‡”„Ž‡†•‘ˆƒŽŽˆ‘”—Žƒ–‹‘•
–Š‡ ˆŽ‘™ƒ„‹Ž‹–› ‘ˆ –Š‡ „Ž‡† „‡ˆ‘”‡ ‘’”‡••‹‘Ǥ Š‡ Šƒ˜‡ ‰‘‘† ˆŽ‘™ ’”‘’‡”–‹‡•Ǥ Š‡ ”‡•—Ž–• ƒ”‡ •—ƒ”‹•‡† ‹
˜ƒ”‹‘—•’”‡ ‘’”‡••‹‘‡˜ƒŽ—ƒ–‹‘•™‡”‡ƒ•ˆ‘ŽŽ‘™•ǣ ƒ„Ž‡͵Ǥ
– ™ƒ• ‡˜‹†‡– ˆ”‘ –Š‡ ”‡•—Ž–• ‘ˆ –Š‡ ’”‡ ‘’”‡••‹‘
1. Angle of Repose •–—†‹‡•ǡ –Šƒ– –Š‡ ’‘™†‡” „Ž‡†• ‘ˆ ƒŽŽ ‡‹‰Š– ˆ‘”—Žƒ–‹‘•
Š‡ ƒ‰Ž‡ ‘ˆ ”‡’‘•‡ ƒ „‡ ‘””‡Žƒ–‡† ™‹–Š –›’‡ ‘ˆ ˆŽ‘™ ’‘••‡• ‰‘‘† ˆŽ‘™ ’”‘’‡”–‹‡•ǡ ™Š‹ Š ™‡”‡ ™‹–Š‹ –Š‡
’‘™†‡”Ǥ Š‡ ƒ‰Ž‡ ‘ˆ ”‡’‘•‡ „‡Ž‘™ ʹͷͲ ‹†‹ ƒ–‡ ‡š ‡ŽŽ‡– •–ƒ†ƒ”† Ž‹‹–• ƒ† ™‡”‡ “—ƒŽ‹ˆ‹‡† ˆ‘” ‘’”‡••‹‘ ‹–‘
ˆŽ‘™ ’”‘’‡”–‹‡•Ǥ Š‡ ƒ‰Ž‡ ”‡’‘•‡ ‘ˆ ƒŽŽ –Š‡ ˆ‘”—Žƒ–‹‘• ƒ„Ž‡–•Ǥ
”ƒ‰‡• ˆ”‘ ʹͳǏǤͺͲǯ –‘ ʹͷǏǤͶ͸ǯǤ – ™ƒ• ‡˜‹†‡– ˆ”‘ –Š‡ 
”‡•—Ž–•ǡ –Šƒ– –Š‡’‘™†‡” „Ž‡†•‘ˆ ƒŽŽˆ‘”—Žƒ–‹‘• ’‘••‡•ǯ Post Compression Evaluations
‰‘‘†ˆŽ‘™’”‘’‡”–‹‡•ǤŠ‡”‡•—Ž–•‘ˆƒ‰Ž‡‘ˆ”‡’‘•‡ˆ‘”ƒŽŽ Š‡–ƒ„Ž‡–•‘„–ƒ‹‡†ƒˆ–‡” ‘’”‡••‹‘™‡”‡‡˜ƒŽ—ƒ–‡†‘
–Š‡ˆ‘”—Žƒ–‹‘•ƒ”‡•—ƒ”‹•‡†‹ƒ„Ž‡͵Ǥ ˜ƒ”‹‘—• ’ƒ”ƒ‡–‡”• –‘ †‡–‡”‹‡ –Š‡‹” “—ƒŽ‹–› ƒ† –‘
 ‡•—”‡ –Šƒ– –Š‡ ”‡•—Ž–ƒ– ’”‘†— – ‡‡–• ƒŽŽ ‡ ‡••ƒ”›
2. Bulk Density ”‹–‡”‹ƒǯ•”‡“—‹”‡†ˆ‘”–Š‡ˆƒ•–†‹••‘Ž˜‹‰–ƒ„Ž‡–•Ǥ
Š‡„—Ž†‡•‹–›™ƒ•†‡–‡”‹‡†–‘ƒ••‡••–Š‡ˆ”‡‡ˆŽ‘™‹‰ 
’”‘’‡”–› ‘ˆ –Š‡ ’‘™†‡” „Ž‡†Ǥ Š‡ „—Ž †‡•‹–› ‘ˆ ƒŽŽ 1. Weight Variation Test
ˆ‘”—Žƒ–‹‘• ”ƒ‰‡• ˆ”‘ ͲǤʹͻ‰Ȁ ͵ –‘ ͲǤ͵͵ ‰Ȁ ͵Ǥ Š‡ Š‡ ™‡‹‰Š– ˜ƒ”‹ƒ–‹‘ ‘ˆ –Š‡ ˆ‘”—Žƒ–‹‘ ͳ –‘ ͳʹ ”ƒ‰‡†
”‡•—Ž–• ‹†‹ ƒ–‡ –Šƒ– –Š‡ ’‘™†‡” „Ž‡†• ‘ˆ ƒŽŽ ˆ‹ˆ–‡‡ ˆ”‘ͳͶ͸Ǥͷ–‘ͳͷͲǤͷ‰ǤŠ‡’‡” ‡–ƒ‰‡†‡˜‹ƒ–‹‘‘ˆ–ƒ„Ž‡–•
ˆ‘”—Žƒ–‹‘•™‡”‡Šƒ˜‹‰‰‘‘†ˆŽ‘™’”‘’‡”–‹‡•ǤŠ‡”‡•—Ž–• Šƒ• –‘ „‡ •’‡ ‹ˆ‹  ƒ† –Š‡› •Š‘—Ž† ‘– †‹ˆˆ‡” ά ͹Ǥͷ Ψ
ƒ”‡•—ƒ”‹•‡†‹ƒ„Ž‡͵Ǥ ƒ ‘”†‹‰ –‘  •’‡ ‹ˆ‹ ƒ–‹‘Ǥ Š‡ ”‡•—Ž–• ƒ”‡ •Š‘™ ‹
ƒ„Ž‡ͶǤ
3. Tapped Density 
Š‡ –ƒ’’‡† †‡•‹–› ‘ˆ ’‘™†‡” ‹• ‹’‘”–ƒ– ’ƒ”ƒ‡–‡”• ‹ 2. Hardness
‘’”‡••‹„‹Ž‹–›‘ˆ–Š‡’‘™†‡”ǤŠ‡–ƒ’’‡††‡•‹–›‘ˆƒŽŽ–Š‡ Š‡Šƒ”†‡••‘ˆ–Š‡ƒŽŽˆ‘”—Žƒ–‹‘ ͳ–‘ ͳʹ”ƒ‰‡†ˆ”‘
ˆ‘”—Žƒ–‹‘• ”ƒ‰‡• ˆ”‘ ͲǤ͵ʹ‰Ȁ ͵ –‘ ͲǤ͵ͺ‰Ȁ ͵Ǥ ”‘ ͵ǤͲ–‘͵Ǥ͵‰Ȁ ʹǤŠ‡”‡•—Ž–•‹†‹ ƒ–‡–Šƒ––Š‡–ƒ„Ž‡–•‘ˆƒŽŽ
–Š‡ ”‡•—Ž–•ǡ ‹– ™ƒ• ‹ˆ‡””‡† –Šƒ– –Š‡ ’‘™†‡” „Ž‡† ‘ˆ ƒŽŽ ˆ‘”—Žƒ–‹‘• Šƒ˜‡ —‹ˆ‘” Šƒ”†‡••Ǥ Š‡ ”‡•—Ž–• ™‡”‡
ˆ‘”—Žƒ–‹‘•’‘••‡•‰‘‘†ˆŽ‘™’”‘’‡”–‹‡•ǤŠ‡”‡•—Ž–•‘ˆƒŽŽ •Š‘™‹ƒ„Ž‡ͶǤ
–Š‡ˆ‘”—Žƒ–‹‘•ƒ”‡•—ƒ”‹•‡†‹ƒ„Ž‡͵Ǥ 
 3. Friability Test
4. Compressibility Index Š‡ ˆ”‹ƒ„‹Ž‹–› ‘ˆ –Š‡ –ƒ„Ž‡– ™ƒ• ˆ‘—† –‘ „‡ Ž‡•• –Šƒ ͳΨ
Š‡ ‘’”‡••‹„‹Ž‹–› ‹†‡š ™ƒ• –Š‡ •‹’Ž‡•– ‡–Š‘† –‘ ™Š‹ Š ™ƒ• ‘•‹†‡”‡† ™‹–Š‹ –Š‡ Ž‹‹– ȋȌǤ Š‡ ”‡•—Ž–•
‡ƒ•—”‡ –Š‡ ˆ”‡‡ ˆŽ‘™‹‰ ‘ˆ ’‘™†‡” „Ž‡†• ‘ˆ ƒŽŽ ‹†‹ ƒ–‡ –Šƒ– –Š‡ ˆ”‹ƒ„‹Ž‹–› ˆ‘” –ƒ„Ž‡–• ‘ˆ ƒŽŽ ˆ‘”—Žƒ–‹‘•

˜‡–‹ƒ’‹†ǣŠƒ”‡ Š‘ŽǤʹͲʹͲǡ ••—‡͵ 7 ʹͲʹͲ’’–͵ͳͶͺʹ ̹ ˜‡–‹ ‘—”ƒŽ•ȋȌ–†


ȏ Ͳͻ͹͸Ǧ͵͹ͺ͵Ȑ —„Ž‹•Š‡†‘‡„ʹ͸ȀͲͶȀʹͲʹͲǡ™™™Ǥ‹˜‡–‹Ǥ‹
  

Table 4: Post compression studies of Oseltamivir Fast Dissolving Tablet

Formulation Average Hardness Friability Thickness Drug Content Disintegration Wetting


Code Weight (mg) (kg/cm2) (%) (mm) (%) Time (sec) Time (sec )
ͳ ͳͶͺǤͷ ͵Ǥʹ ͲǤͺͶ ͵ ͻͺǤʹͳ ͵ͺ ͳͺ
ʹ ͳͶ͸Ǥͷ ͵Ǥʹ ͲǤ͸ͺ ͵ ͻ͹Ǥ͸ͻ ʹͻ ͳͻ
͵ ͳͶ͹Ǥͷ ͵Ǥʹ ͲǤͺͶ ͵ ͻͺǤͺ͹ ʹʹ ͳͶ
Ͷ ͳͶͻ ͵Ǥʹ ͲǤ͵͵ ͵ ͻͻǤ͸ͻ ͳʹ ͳͲ
ͷ ͳͶͷǤͷ ͵Ǥʹ ͲǤͺ͸ ͵ ͻ͸ǤͲͲ Ͷͷ ͳͷ
͸ ͳͶ͹Ǥͷ ͵ǤͲ ͲǤ͸ͳ ͵ ͻ͹Ǥ͹ͷ ͵ͳ ͳͶ
͹ ͳͶͺ ͵ǤͲ ͲǤͶ͵ ͵ ͻͻǤͺ͹ ʹ͵ ͳͲ
ͺ ͳͶͺǤͷ ͵ǤͲ ͲǤ͸͹ ͵ ͻͻǤͶʹ ͳͶ ͺ
ͻ ͳͷͲǤͷ ͵Ǥ͵ ͲǤ͸Ͷ ͵ ͻ͹Ǥ͸ͻ ͵͸ ʹͲ
ͳͲ ͳͶͻǤͷ ͵Ǥ͵ ͲǤͷ͵ ͵ ͻ͹Ǥ͵Ͳ ʹͳ ͳͷ
ͳͳ ͳͷͲ ͵Ǥʹ ͲǤ͵͵ ͵ ͻͻǤʹ͵ ͳ͹ ͳͳ
ͳʹ ͳͶͻ ͵Ǥʹ ͲǤͺ͵ ͵ ͻͻǤ͸ͳ ͳʹ ͳͲ



Wetting Time Profile


ʹͷ

ʹͲ
Time ( Sec )

ͳͷ

ͳͲ

Ͳ
ͳ ʹ ͵ Ͷ ͷ ͸ ͹ ͺ ͻ ͳͲ ͳͳ ͳʹ

Formulation Code

Figure 14:‡––‹‰–‹‡’”‘ˆ‹Ž‡

™‡”‡„‡Ž‘™ͳΨƒ†Š‡ ‡’ƒ••‡•–Š‡–‡•–ǤŠ‡”‡•—Ž–•ƒ”‡ ™‡––‹‰ –‹‡ ‘ˆ ƒŽŽ –ƒ„Ž‡–• ™‡”‡ ™‹–Š‹ –Š‡ Ž‹‹–•Ǥ Š‡
•Š‘™‹ƒ„Ž‡ͶǤ ”‡•—Ž–•ƒ”‡•Š‘™‹ƒ„Ž‡ͶǤ
 
4. Thickness 7. Disintegration Time
Š‡’‡” ‡–ƒ‰‡†‡˜‹ƒ–‹‘‘ˆ–Š‹ ‡••‘ˆ–Š‡ˆ‘”—Žƒ–‹‘ ͳ Š‡†‹•‹–‡‰”ƒ–‹‘–‹‡™ƒ•–Š‡–‹‡–ƒ‡„›–Š‡–ƒ„Ž‡––‘
–‘ ͳʹ ”ƒ‰‡† ˆ”‘ ͵ǤŠ‡ ”‡•—Ž–• ‹†‹ ƒ–‡ –Šƒ– –Š‡ „”‡ƒ †‘™ ‹ –‘ •ƒŽŽ ’ƒ”–‹ Ž‡•ǡ ‹ –Š‡ ’”‡•‡ ‡ ‘ˆ
ƒ„Ž‡–•‘ˆƒŽŽˆ‘”—Žƒ–‹‘•™‡”‡‘ˆ—‹ˆ‘”•‹œ‡ǤŠ‡”‡•—Ž–• ƒ“—‡‘—• ‡†‹—Ǥ – ˜ƒ”‹‡• ™‹–Š –›’‡ ƒ† ‘ ‡–”ƒ–‹‘ ‘ˆ
ƒ”‡•Š‘™‹ƒ„Ž‡ͶǤ –Š‡ •—’‡”†‹•‹–‡‰”ƒ–• ‹ ‘”’‘”ƒ–‡† ‹ –Š‡ ˆ‘”—Žƒ–‹‘Ǥ
Š‡†‹•‹–‡‰”ƒ–‹‘–‹‡ˆ‘”ˆ‘”—Žƒ–‹‘• ͳǡ ʹǡ ͵ǡ Ͷǡ ͷǡ
5. Drug Content ͸ǡ ͹ǡ ͺǡ ͻǡ ͳͲǡ ͳͳƒ† ͳʹ™ƒ•ˆ‘—†–‘„‡͵ͺǡʹͻǡʹʹǡ
Š‡ —‹ˆ‘”‹–› ‹ –Š‡ †”—‰ ‘–‡– ‹• ƒ ‹’‘”–ƒ– ͳʹǡ Ͷͷǡ ͵ͳǡ ʹ͵ǡ ͳͶǡ ͵͸ǡ ʹͳǡ ͳ͹ǡ ͳʹ ”‡•’‡ –‹˜‡Ž›Ǥ Š‡ ”‡•—Ž–•
‡ƒ•—”‡ǤŠ‡ ‘–‡–—‹ˆ‘”‹–›™ƒ•ˆ‘—†™‹–Š‹ͻ͸ǤͲͲΨ ‹†‹ ƒ–‡ –Šƒ– –Š‡ †‹•‹–‡‰”ƒ–‹‘ –‹‡ ˆ‘” –ƒ„Ž‡–• ‘ˆ ƒŽŽ
–‘ͻͻǤͺ͹Ψ‘ˆ–Š‡͹ͷ‰‘ˆ‘•‡Ž–ƒ‹˜‹”ǤŠ‡”‡•—Ž–•‹†‹ ƒ–‡ ˆ‘”—Žƒ–‹‘• ƒ”‡ ™‹–Š‹ –Š‡ Ž‹‹–• ™‡”‡ ™‹–Š‹ –Š‡
–Šƒ– –Š‡ ‘–‡–• ˆ‘” –ƒ„Ž‡–• ‘ˆ ƒŽŽ ˆ‘”—Žƒ–‹‘• ™‡”‡ ’‡”‹••‹„Ž‡ Ž‹‹–•ǡ ™Š‹ Š ‹†‹ ƒ–‡ –Šƒ– –Š‡ ƒ„Ž‡–• ‘ˆ ƒŽŽ
—‹ˆ‘” ƒ† ‘–ƒ‹• –Š‡”ƒ’‡—–‹  †‘•‡ ‘ˆ –Š‡ ƒ –‹˜‡ ˆ‘”—Žƒ–‹‘•†‹•‹–‡‰”ƒ–‡“—‹ Ž›ǤŠ‡”‡•—Ž–•ƒ”‡•Š‘™‹
‹‰”‡†‹‡–ǤŠ‡”‡•—Ž–•ƒ”‡•Š‘™‹ƒ„Ž‡ͶǤ ƒ„Ž‡ͶǤ
 
6. Wetting Time 8. Dissolution Study
Š‡ ™‡––‹‰ –‹‡ ‹†‹ ƒ–‡• –Š‡ ƒ’ƒ ‹–› ‘ˆ –Š‡ Š‡in-vitro†”—‰”‡Ž‡ƒ•‡ Šƒ”ƒ –‡”‹•–‹ •™‡”‡•–—†‹‡†‹’ 
•—’‡”†‹•‹–‡‰”ƒ–•–‘ƒ„•‘”„™ƒ–‡”ƒ† ‘’Ž‡–‡Ž›™‡––Š‡ ͸Ǥͺ Š‘•’Šƒ–‡ „—ˆˆ‡” ˆ‘” ͵Ͳ ‹ —•‹‰  –›’‡Ǧͳͳ
–ƒ„Ž‡– ƒ– –Š‡ ‡ƒ”Ž‹‡•– –‹‡ ’‘••‹„Ž‡ǡ ™Š‹ Š ™‡”‡ –Š‡ †‹••‘Ž—–‹‘ ƒ’’ƒ”ƒ–—•Ǥ In-vitro †‹••‘Ž—–‹‘ †ƒ–ƒ ‘ˆ
•‹‰‹ˆ‹ ƒ– Šƒ”ƒ –‡”‹•–‹ • ‘ˆ ˆƒ•– †‹••‘Ž˜‹‰ –ƒ„Ž‡–•Ǥ Š‡ ˆ‘”—Žƒ–‹‘ •Š‘™‡† –Šƒ–ǡ ˆ‘”—Žƒ–‹‘ ͳǡ ʹǡ ͵ ƒ† Ͷ
–ƒ„Ž‡– ™ƒ• ‹‹— ™‡––‹‰ –‹‡ ™‹ŽŽ ‡ƒ„Ž‡ ˆƒ•–‡” ”‡Ž‡ƒ•‡† ͺͶǤ͵ͺΨǡ ͻ͵ǤͻʹΨǡ ͻͺǤͷ͸Ψ ƒ† ͻͻǤͺʹΨ †”—‰
†‹•‹–‡‰”ƒ–‹‘ ‘ˆ –Š‡ –ƒ„Ž‡–•ǡ ™Š‹ Š ‹• ‘•– ‹’‘”–ƒ– ”‡•’‡ –‹˜‡Ž› ™‹–Š‹ ͵Ͳ ‹Ǥ Š‡ ˆ‘”—Žƒ–‹‘ Ͷ ™‹–Š
”‹–‡”‹ƒ ˆ‘” ˆƒ•– †‹••‘Ž˜‹‰ –ƒ„Ž‡–Ǥ Š‡ ™‡––‹‰ –‹‡ ˆ‘” ‘ ‡–”ƒ–‹‘ ‘ˆ ͳͷΨ ”‘•’‘˜‹†‘‡ ™ƒ• ˆ‘—† –‘ „‡ –Š‡
ˆ‘”—Žƒ–‹‘• ͳǡ ʹǡ ͵ǡ Ͷǡ ͷǡ ͸ǡ ͹ǡ ͺǡ ͻǡ ͳͲǡ ͳͳƒ† „‡•– ˆ‘”—Žƒ–‹‘Ǥ ”—‰ ”‡Ž‡ƒ•‡ ‘ˆ ͻͻǤͺʹ ™Š‹ Š ™ƒ• –Š‡
ͳʹ™‡”‡ˆ‘—†–‘„‡ͳͺǡͳͻǡͳͶǡͳͲǡͳͷǡͳͶǡͳͲǡͺǡʹͲǡͳͷǡ Š‹‰Š‡•– ‘ˆ ƒŽŽ ˆ‘—” ˆ‘”—Žƒ–‹‘•Ǥ ”ƒ’Š ‹• •Š‘™ ‹ ‹‰—”‡
ͳͳǡͳͲ•‡ ‘†•”‡•’‡ –‹˜‡Ž›ǤŠ‡•‡”‡•—Ž–•‹†‹ ƒ–‡–Šƒ––Š‡ ͳͷǤ

˜‡–‹ƒ’‹†ǣŠƒ”‡ Š‘ŽǤʹͲʹͲǡ ••—‡͵ 8 ʹͲʹͲ’’–͵ͳͶͺʹ ̹ ˜‡–‹ ‘—”ƒŽ•ȋȌ–†


ȏ Ͳͻ͹͸Ǧ͵͹ͺ͵Ȑ —„Ž‹•Š‡†‘‡„ʹ͸ȀͲͶȀʹͲʹͲǡ™™™Ǥ‹˜‡–‹Ǥ‹
  

Table 5: In-Vitro Dissolution Data of Formulation F1, F2, F3 and F4 (Crospovidone)

Percentage Cumulative Drug Release ( % )


S. No. Time (min )
F1 F2 F3 F4
1 Ͳ Ͳ Ͳ Ͳ Ͳ
2 ͷ ͳ͹ǤͶͷ ͵ͶǤ͵͸ ͵͸ǤͷͲ ͵ͶǤͺ͵
3 ͳͲ ͵ͶǤͷ͸ ͶʹǤͷʹ ͶͶǤͲ͸ ͷͻǤͷ͵
4 ͳͷ ͶͷǤͶ͸ ͷͺǤͶ͵ ͹ʹǤ͹Ͳ ͺ͸Ǥ͵͵
5 ʹͲ ͸ͲǤ͵Ͷ ͹͵Ǥʹͺ ͺ͹Ǥͷͻ ͻͷǤͶͷ
6 ʹͷ ͹͸Ǥ͸ʹ ͺͶǤ͹ͷ ͻͺǤͳͶ ͻͺǤͳͺ
7 ͵Ͳ ͺͶǤ͵ͺ ͻ͵Ǥͻʹ ͻͺǤͷ͸ ͻͻǤͺʹ

Table 6: In-Vitro Dissolution Data of Formulations F5, F6, F7 and F8 (Xanthan Gum)

Percentage Cumulative Drug Release ( % )


S. No. Time (min )
F5 F6 F7 F8
ͳ Ͳ Ͳ Ͳ Ͳ Ͳ
ʹ ͷ ͳͲǤͺ͵ ͳʹǤͳ͵ ͳ͹Ǥͷ͵ ͳ͵Ǥͻͻ
͵ ͳͲ ʹͳǤ͸ͳ ʹͷǤͳͳ ͵ͺǤ͵ͷ ʹͺǤ͵ͳ
Ͷ ͳͷ ͵ͶǤͺͶ ͶͲǤ͹ʹ ͶͺǤͲ͸ ͶͲǤͲ͹
ͷ ʹͲ Ͷ͹Ǥʹ͹ ͷͻǤ͹ʹ ͸ͻǤ͸͸ ͷͺǤ͵͵
͸ ʹͷ ͸ͲǤͲͷ ͺͷǤ͵ͺ ͺͺǤͲ͵ ͺ͵ǤͺͲ
͹ ͵Ͳ ͺ͵Ǥͻͺ ͺͺǤͳ͹ ͻͺǤʹ͹ ͻ͸ǤͶ͸
 

In vitro drug release profile


ͳʹͲ
ͳͲͲ
% Drug Release

ͺͲ
͸Ͳ
ͶͲ
ʹͲ
Ͳ
Ͳ ͷ ͳͲ ͳͷ ʹͲ ʹͷ ͵Ͳ ͵ͷ

Time (min)
ͳ ʹ ͵ Ͷ
Figure 15: In-vitro†‹••‘Ž—–‹‘†ƒ–ƒ‘ˆˆ‘”—Žƒ–‹‘ ͳǡ ʹǡ ͵ƒ† Ͷȋ ”‘•’‘˜‹†‘‡Ȍ

In vitro drug release profile


ͳʹͲ
ͳͲͲ
% Drug Release

ͺͲ
͸Ͳ
ͶͲ
ʹͲ
Ͳ
Ͳ ͷ ͳͲ ͳͷ ʹͲ ʹͷ ͵Ͳ ͵ͷ

Time (min)

ͷ ͸ ͹ ͺ

Figure 16: In-vitro †‹••‘Ž—–‹‘†ƒ–ƒ‘ˆˆ‘”—Žƒ–‹‘• ͷǡ ͸ǡ ͹ƒ† ͺȋƒ–Šƒ —Ȍ

Š‡in-vitro†”—‰”‡Ž‡ƒ•‡ Šƒ”ƒ –‡”‹•–‹ •™‡”‡•–—†‹‡†‹ ”‡•’‡ –‹˜‡Ž› ™‹–Š‹ ͵Ͳ ‹Ǥ Š‡ ˆ‘”—Žƒ–‹‘ ͹ ™‹–Š
’  ͸Ǥͺ Š‘•’Šƒ–‡ „—ˆˆ‡” ˆ‘” ͵Ͳ ‹ —•‹‰  –›’‡Ǧͳͳ ‘ ‡–”ƒ–‹‘ ‘ˆ ͳʹΨ ƒ–Šƒ ‰— ™ƒ• ˆ‘—† –‘ „‡ –Š‡
†‹••‘Ž—–‹‘ ƒ’’ƒ”ƒ–—•Ǥ In-vitro †‹••‘Ž—–‹‘ †ƒ–ƒ ‘ˆ „‡•– ˆ‘”—Žƒ–‹‘Ǥ ”—‰ ”‡Ž‡ƒ•‡ ‘ˆ ͻͺǤʹ͹ ™Š‹ Š ™ƒ• –Š‡
ˆ‘”—Žƒ–‹‘ •Š‘™‡† –Šƒ–ǡ ˆ‘”—Žƒ–‹‘ ͷǡ ͸ǡ ͹ ƒ† ͺ Š‹‰Š‡•– ‘ˆ ƒŽŽ ˆ‘—” ˆ‘”—Žƒ–‹‘•Ǥ ”ƒ’Š ‹• •Š‘™ ‹ ‹‰—”‡
”‡Ž‡ƒ•‡† ͺ͵ǤͻͺΨǡ ͺͺǤͳ͹Ψǡ ͻͺǤͳ͹Ψ ƒ† ͻ͸ǤͶ͸Ψ †”—‰ ͳ͸Ǥ

˜‡–‹ƒ’‹†ǣŠƒ”‡ Š‘ŽǤʹͲʹͲǡ ••—‡͵ 9 ʹͲʹͲ’’–͵ͳͶͺʹ ̹ ˜‡–‹ ‘—”ƒŽ•ȋȌ–†


ȏ Ͳͻ͹͸Ǧ͵͹ͺ͵Ȑ —„Ž‹•Š‡†‘‡„ʹ͸ȀͲͶȀʹͲʹͲǡ™™™Ǥ‹˜‡–‹Ǥ‹
  

Table 7: In-Vitro Dissolution Data of Formulations F9, F10, F11 and F12 (Crospvidone + Xanthan Gum)

Percentage Cumulative Drug Release ( % )


S. No. Time (min )
F9 F10 F11 F12
ͳ Ͳ Ͳ Ͳ Ͳ Ͳ
ʹ ͷ ͵͵ǤͻͲ ͵͵ǤͺͶ ͵ͶǤʹ͸ ͵ͻǤͶ͸
͵ ͳͲ Ͷ͵Ǥ͸ͳ Ͷ͵Ǥͷ͸ ͶͷǤ͸͵ Ͷ͸Ǥ͵ͺ
Ͷ ͳͷ ͷ͵Ǥ͵͵ ͷͶǤͲͲ ͷ͸ǤͲ͹ ͹ͻǤͷͲ
ͷ ʹͲ ͸͵Ǥ͸ͻ ͸͹ǤͺͲ ͹ͺǤͶ͸ ͻ͵Ǥͳʹ
͸ ʹͷ ͹ͺǤͷͳ ͹ͺǤͻʹ ͺͺǤ͸ͳ ͻͻǤͺͶ
͹ ͵Ͳ ͺͺǤ͸ͳ ͺͻǤ͵Ͳ ͻͷǤ͵ͺ 

Table 8: In-Vitro Dissolution Data of Formulations F1 to F12

S. Time Percentage Cumulative Drug Release ( % )


No. (min ) F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12
ͳ Ͳ Ͳ Ͳ Ͳ Ͳ Ͳ Ͳ Ͳ Ͳ Ͳ Ͳ Ͳ Ͳ
ʹ ͷ ͳ͹ǤͶͷ ͵ͶǤ͵͸ ͵͸ǤͷͲ ͵ͶǤͺ͵ ͳͲǤͺ͵ ͳʹǤͳ͵ ͳ͹Ǥͷ͵ ͳ͵Ǥͻͻ ͵͵ǤͻͲ ͵͵ǤͺͶ ͵ͶǤʹ͸ ͵ͻǤͶ͸
͵ ͳͲ ͵ͶǤͷ͸ ͶʹǤͷʹ ͶͶǤͲ͸ ͷͻǤͷ͵ ʹͳǤ͸ͳ ʹͷǤͳͳ ͵ͺǤ͵ͷ ʹͺǤ͵ͳ Ͷ͵Ǥ͸ͳ Ͷ͵Ǥͷ͸ ͶͷǤ͸͵ Ͷ͸Ǥ͵ͺ
Ͷ ͳͷ ͶͷǤͶ͸ ͷͺǤͶ͵ ͹ʹǤ͹Ͳ ͺ͸Ǥ͵͵ ͵ͶǤͺͶ ͶͲǤ͹ʹ ͶͺǤͲ͸ ͶͲǤͲ͹ ͷ͵Ǥ͵͵ ͷͶǤͲͲ ͷ͸ǤͲ͹ ͹ͻǤͷͲ
ͷ ʹͲ ͸ͲǤ͵Ͷ ͹͵Ǥʹͺ ͺ͹Ǥͷͻ ͻͷǤͶͷ Ͷ͹Ǥʹ͹ ͷͻǤ͹ʹ ͸ͻǤ͸͸ ͷͺǤ͵͵ ͸͵Ǥ͸ͻ ͸͹ǤͺͲ ͹ͺǤͶ͸ ͻ͵Ǥͳʹ
͸ ʹͷ ͹͸Ǥ͸ʹ ͺͶǤ͹ͷ ͻͺǤͳͶ ͻͺǤͳͺ ͸ͲǤͲͷ ͺͷǤ͵ͺ ͺͺǤͲ͵ ͺ͵ǤͺͲ ͹ͺǤͷͳ ͹ͺǤͻʹ ͺͺǤ͸ͳ ͻͻǤͺͶ
͹ ͵Ͳ ͺͶǤ͵ͺ ͻ͵Ǥͻʹ ͻͺǤͷ͸ ͻͻǤͺʹ ͺ͵Ǥͻͺ ͺͺǤͳ͹ ͻͺǤʹ͹ ͻ͸ǤͶ͸ ͺͺǤ͸ͳ ͺͻǤ͵Ͳ ͻͷǤ͵ͺ ͻͻǤͻͻ


In vitro drug release profile


ͳʹͲ

ͳͲͲ
% Drug Release

ͺͲ

͸Ͳ

ͶͲ

ʹͲ

Ͳ
Ͳ ͷ ͳͲ ͳͷ ʹͲ ʹͷ ͵Ͳ ͵ͷ
Time (min)
ͻ ͳͲ ͳͳ ͳʹ

Figure 17:In-vitro †‹••‘Ž—–‹‘†ƒ–ƒ‘ˆˆ‘”—Žƒ–‹‘ ͻǡ ͳͲǡ ͳͳƒ† ͳʹ



Figure 18: In-vitro †‹••‘Ž—–‹‘†ƒ–ƒ‘ˆˆ‘”—Žƒ–‹‘ ͳ–‘ ͳʹ

Š‡in-vitro†”—‰”‡Ž‡ƒ•‡ Šƒ”ƒ –‡”‹•–‹ •™‡”‡•–—†‹‡†‹ ”‡•’‡ –‹˜‡Ž› ™‹–Š‹ ͵Ͳ ‹ǤŠ‡ ˆ‘”—Žƒ–‹‘ ͳʹ ™‹–Š
’  ͸Ǥͺ Š‘•’Šƒ–‡ „—ˆˆ‡” ˆ‘” ͵Ͳ ‹ —•‹‰  –›’‡Ǧͳͳ ‘ ‡–”ƒ–‹‘ ‘ˆ ͳͷΨ ”‘•’‘˜‹†‘‡ Ϊƒ–Šƒ ‰— ™ƒ•
†‹••‘Ž—–‹‘ ƒ’’ƒ”ƒ–—•Ǥ In-vitro †‹••‘Ž—–‹‘ †ƒ–ƒ ‘ˆ ˆ‘—† –‘ „‡ –Š‡ „‡•– ˆ‘”—Žƒ–‹‘Ǥ ”—‰ ”‡Ž‡ƒ•‡ ‘ˆ ͻͻǤͺͶ
ˆ‘”—Žƒ–‹‘•Š‘™‡†–Šƒ–ǡˆ‘”—Žƒ–‹‘ ͻǡ ͳͲǡ ͳͳƒ† ͳʹ ™‹–Š‹ ʹͷ ‹ ™Š‹ Š ™ƒ• –Š‡ Š‹‰Š‡•– ‘ˆ ƒŽŽ ˆ‘—”
”‡Ž‡ƒ•‡† ͺͺǤ͸ͳΨǡ ͺͻǤ͵ͲΨǡ ͻͷǤ͵ͺΨ ƒ† ͻͻǤͺͶΨ †”—‰ ˆ‘”—Žƒ–‹‘•Ǥ ”ƒ’Š‹••Š‘™‹ ‹‰—”‡ͳ͹Ǥ

˜‡–‹ƒ’‹†ǣŠƒ”‡ Š‘ŽǤʹͲʹͲǡ ••—‡͵ 10 ʹͲʹͲ’’–͵ͳͶͺʹ ̹ ˜‡–‹ ‘—”ƒŽ•ȋȌ–†


ȏ Ͳͻ͹͸Ǧ͵͹ͺ͵Ȑ —„Ž‹•Š‡†‘‡„ʹ͸ȀͲͶȀʹͲʹͲǡ™™™Ǥ‹˜‡–‹Ǥ‹
  

Š‡†‹••‘Ž—–‹‘•–—†‹‡•™‡”‡’‡”ˆ‘”‡†–‘‡˜ƒŽ—ƒ–‡–Š‡ ͸Ǥ Šƒ–—  ǡ ƒ‡ Ǥ Š‡ –‡ Š‘Ž‘‰‹‡• —•‡† ˆ‘” †‡˜‡Ž‘’‹‰
”‡Ž‡ƒ•‡’”‘ˆ‹Ž‡‘ˆ–Š‡†”—‰ǡ™Š‹ Š”‡Žƒ–‡•–Š‡’‡” ‡–ƒ‰‡‘ˆ ‘”ƒŽŽ›†‹•‹–‡‰”ƒ–‹‰–ƒ„Ž‡–•ǣ”‡˜‹‡™Ǥ –ƒŠƒ”ǡ͸ͳȋͳȌǣͳͳ͹Ǧ
†”—‰”‡Ž‡ƒ•‡ˆ”‘‹–•†‘•ƒ‰‡ˆ‘”™‹–Š–Š‡ˆ— –‹‘‘ˆ–‹‡Ǥ ͳ͵ͻǡʹͲͳͳǤ
Š‡ •—’‡”†‹•‹–‡‰”ƒ–• ™‡”‡ ƒ††‡† –‘ –Š‡ •‘Ž‹† †‘•ƒ‰‡ ͹Ǥ —”‡†”ƒ  ǡ ›‡”  Ǥ ƒ•– †‹••‘Ž˜‹‰ –ƒ„Ž‡– —•‹‰ •‘Ž‹†
†‹•’‡”•‹‘ –‡ Š‹“—‡ǣ ƒ ‘˜‡”˜‹‡™Ǥ †‘ ‡”‹ ƒ ‘—”ƒŽ ‘ˆ
ˆ‘”—Žƒ–‹‘• –‘ ‡Šƒ ‡ –Š‡ †‹•‹–‡‰”ƒ–‹‘ –‹‡ ƒ† Šƒ”ƒ ‡—–‹ ƒŽ‡•‡ƒ” ŠǡͷȋʹȌǣ͸͸ͺǦ͸͹ʹǡʹͲͳͷǤ
–Š‡”‡„›‡Šƒ ‹‰–Š‡ˆƒ•–‡””‡Ž‡ƒ•‡‘ˆƒ –‹˜‡†”—‰ˆ”‘‹–• ͺǤ ƒ–’—–‡ǡ‘—”Ǥ ‘”—Žƒ–‹‘ƒ†‹Ǧ˜‹–”‘‡˜ƒŽ—ƒ–‹‘‘ˆ
†‘•ƒ‰‡ ˆ‘”Ǥ Š‡ †‡•‹”‡† “—ƒŽ‹–› ‘ˆ ˆƒ•– †‹••‘Ž˜‹‰ –ƒ„Ž‡–• ˆƒ•–†‹••‘Ž˜‹‰–ƒ„Ž‡–‘ˆ‡–”‘’”’Ž‘Ž–ƒ”–”ƒ–‡Ǥ”ƒœ‹Ž‹ƒ ‘—”ƒŽ
™ƒ• –‘ Šƒ˜‡ ƒ ƒš‹— ”‡Ž‡ƒ•‡ ‘ˆ –Š‡”ƒ’‡—–‹  †‘•‡ ƒ– ƒ ‘ˆ’Šƒ”ƒ ‡—–‹ ƒŽ ‹‡ ‡•ǡͶͻȋͶȌǣ͹ͺͶǦ͹ͻͳǡʹͲͳ͵Ǥ
˜‡”›‹‹ƒŽ–‹‡’‡”‹‘†ǤŠ‡ƒš‹—†”—‰”‡Ž‡ƒ•‡ƒ–ƒ ͻǤ ƒ†Šƒ˜  ǡ ƒ—†‡™ƒ”  ǡ ƒ‹™ƒ”  ǡ ƒ†Šƒ˜  ǡ
–‹‡’‡”‹‘†‘ˆ͵Ͳ‹—–‡•‹•‘–‡†ˆ‘”ƒŽŽ–Š‡ˆ‘”—Žƒ–‹‘•Ǥ •Š‹”•ƒ‰ƒ” ǡƒƒ”ƒ”Ǥ ‘”—Žƒ–‹‘ƒ†‡˜ƒŽ—ƒ–‹‘‘ˆ
Š‡†”—‰”‡Ž‡ƒ•‡ˆ‘”–ƒ„Ž‡–•‘ˆƒŽŽˆ‘”—Žƒ–‹‘•”ƒ‰‡•ˆ”‘ †‹•’‡”•‹„Ž‡ –ƒ„Ž‡–• ‘ˆ †‹Ž–‹ƒœ‡ Š›†”‘ ŠŽ‘”‹†‡Ǥ –‡”ƒ–‹‘ƒŽ
ͺͶǤ͵ͺ–‘ͻͻǤͺͶ–Š‡”‡•—Ž–•‹†‹ ƒ–‡–Šƒ––Š‡†”—‰ ”‡Ž‡ƒ•‡‘ˆ ‘—”ƒŽ‘ˆŠƒ”‡ Š‡•‡ƒ” Šǡ͵ȋ͵Ȍǣͳ͵ͳͶȂͳ͵ʹͳǡʹͲͳͳǤ
ͳͲǤ ‡–‡”ǡ—ƒ”ǡƒ–Šƒǡƒ†Š‡‡ǡƒŠ‘‘Ǥ ‘”—Žƒ–‹‘
ƒŽŽ –Š‡ ˆ‘”—Žƒ–‹‘• ™ƒ• ˆ‘—† –‘ „‡ ƒ„‘˜‡ ͺͲ Ψ ‹ ͵Ͳ
ƒ† ‡˜ƒŽ—ƒ–‹‘ ‘ˆ ‘”‘†‹•’‡”•‹„Ž‡ –ƒ„Ž‡–• ‘ˆ Ž‘”‘š‹ ƒǤ
‹—–‡•ǤŠ‡”‡Ž‡ƒ•‡ ”ƒ–‡‘ˆ–Š‡•—’‡”†‹•‹–‡‰”ƒ–•™ƒ•‹ –‡”ƒ–‹‘ƒŽ ‘—”ƒŽ ‘ˆ ”—‰ ‡˜‡Ž‘’‡– ƒ† ‡•‡ƒ” Šǡ
–Š‡‘”†‡”‘ˆ”‘•’‘˜‹†‘‡ǡƒ–Šƒ‰—ƒ†”‘•’‘˜‹†‘‡ ͵ȋͳȌǣʹͺͳȂʹͺͷǡʹͲͳͳǤ
Ϊƒ–Šƒ‰—ǤŠ‡”‡•—Ž–•ƒ”‡•—ƒ”‹•‡†‹ƒ„Ž‡͸ǤŠ‡ ͳͳǤ ”›ƒ ǡ Šƒ”ƒ ǡ —ƒ” ǡ Šƒ†”ƒ  ƒ† ƒ‹•™ƒŽ Ǥ
”‘ –Š‡ ”‡•—Ž–• ‘„–ƒ‹‡† ˆ”‘ –Š‡ ’‘•– ‘’”‡••‹‘ ‘”—Žƒ–‹‘ ƒ† ‡˜ƒŽ—ƒ–‹‘ ‘ˆ ‘—–Š †‹••‘Ž˜‹‰ –ƒ„Ž‡–• ‘ˆ
•–—†‹‡• ‘ˆ –ƒ„Ž‡–• ‘ˆ ƒŽŽ ͳʹ ˆ‘”—Žƒ–‹‘•ǡ –Š‡ ˆ‘”—Žƒ–‹‘ ”ƒ‹–‹†‹‡ Ǥ –‡”ƒ–‹‘ƒŽ ‘—”ƒŽ‘ˆŠƒ”‡ Š‡•‡ƒ” Šǡ
ͳʹ ™‹–Š ‘ ‡–”ƒ–‹‘ ‘ˆ ͳͷΨ ”‘•’‘˜‹†‘‡ Ϊ ƒ–Šƒ ʹȋʹȌǣͳͷ͹ͶȂͳͷ͹͹ǡʹͲͳͲǤ
‰— ™ƒ• ˆ‘—† –‘ „‡ –Š‡ „‡•– ˆ‘”—Žƒ–‹‘ ™‹–Š ƒ ͳʹǤ ƒ”ƒ”ǡƒ”‹ƒ ǡƒ ƒ† ƒŽ†—Ǥ ‘”—Žƒ–‹‘
†‹•‹–‡‰”ƒ–‹‘ –‹‡ ‘ˆ ͳʹ•‡ •ǡ ™‡––‹‰ –‹‡ ‘ˆ ͳͲ•‡ • ƒ† ƒ† ‡˜ƒŽ—ƒ–‹‘ ‘ˆ †‘’‡”‹†‘‡ ˆƒ•– †‹••‘Ž˜‹‰ –ƒ„Ž‡–•Ǥ
†”—‰”‡Ž‡ƒ•‡‘ˆͻͻǤͺͶ™‹–Š‹ʹͷ‹™Š‹ Š™ƒ•–Š‡Š‹‰Š‡•– –‡”ƒ–‹‘ƒŽ ‘—”ƒŽ ‘ˆ Šƒ”‡ Š ‡•‡ƒ” Šǡ ͳȋ͵ȌǣͶͺ͵ȂͶͺ͹ǡ
ʹͲͲͻǤ
‘ˆƒŽŽˆ‘”—Žƒ–‹‘•ǤŠ‡”‡•—Ž–•ƒ”‡•Š‘™‹ƒ„Ž‡ͺǤ ͳ͵Ǥ ‡–Š‹Žƒ–Šƒ ǡ —’‡ƒ‰—–ƒ Ǥ ‘”—Žƒ–‹‘ †‡˜‡Ž‘’‡–
 ƒ† ‡˜ƒŽ—ƒ–‹‘ ‘ˆ ˜‡Žƒˆƒš‹‡ Š›†”‘ ŠŽ‘”‹†‡ ‘”‘†‹•’‡”•‹„Ž‡
CONCLUSION –ƒ„Ž‡–•Ǥ –‡”ƒ–‹‘ƒŽ ‘—”ƒŽ ‘ˆ Šƒ”ƒ ‡—–‹ ƒŽ  ‹‡ ‡ ƒ†
– ™ƒ• ‘ Ž—†‡†ǡ –Šƒ– ‘•‡Ž–ƒ‹˜‹” ƒ „‡ •— ‡••ˆ—ŽŽ› ‡•‡ƒ” ŠǡʹȋͶȌǣͻͳ͵ȂͻʹͳǡʹͲͳͳǤ
ˆ‘”—Žƒ–‡† ƒ• ˆƒ•– †‹••‘Ž˜‹‰ –ƒ„Ž‡–• —•‹‰ ͳͶǤ —’–ƒ  Ǥ ƒ•– †‹••‘Ž˜‹‰ –ƒ„Ž‡–Ǧ ƒ ”‡˜‹‡™Ǥ Š‡ Šƒ”ƒ
•—’‡”†‹•‹–‡‰”ƒ–• ‹Ǥ‡Ǥ ”‘•’‘˜‹†‘‡ǡ šƒ–Šƒ ‰— ƒ† ‘˜ƒ–‹‘ǡͳȋͳȌǣͳǦ͸ǡʹͲͳʹǤ
”‘•’‘˜‹†‘‡Ϊšƒ–Šƒ‰—‹†‹ˆˆ‡”‡– ‘ ‡–”ƒ–‹‘•ȋ͸ǡ ͳͷǤ ƒ‡Ǥ ‘”—Žƒ–‹‘ƒ†‡˜ƒŽ—ƒ–‹‘‘ˆˆƒ•–†‹••‘Ž˜‹‰–ƒ„Ž‡–
ͻǡ ͳʹ ƒ† ͳͷΨȌ „› †‹”‡ – ‘’”‡••‹‘ ‡–Š‘†Ǥ Š‡ ‘ˆƒŽ„‡†ƒœ‘Ž‡Ǥ –‡”ƒ–‹‘ƒŽ—””‡– Šƒ”ƒ ‡—–‹ ƒŽ ‘—”ƒŽǡ
ͳȋͳͲȌǣ͵ͳͳǦ͵ͳ͸ǡʹͲͳʹǤ
ˆ‘”—Žƒ–‹‘ ‘–ƒ‹‹‰ ͳͷΨ ‘ˆ ”‘•’‘˜‹†‘‡ Ϊ šƒ–Šƒ
ͳ͸Ǥ ”ƒ˜ƒ‹ ǡ ƒ‹ŽƒŒƒ  Ǥ ‘”—Žƒ–‹‘ ƒ† ˜ƒŽ—ƒ–‹‘ ‘ˆ ˆƒ•–
‰—ȋ‘„‹ƒ–‹‘Ȍƒ••—’‡”†‹•‹–‡‰”ƒ–•™ƒ•ˆ‘—†–‘„‡ †‹••‘Ž˜‹‰ –ƒ„Ž‡–• ‘ˆ ˆ‡Ž‘†‹’‹‡Ǥ  ‘—”ƒŽ ‘ˆ Šƒ”ƒ ›ǡ
‘—–•–ƒ†‹‰ –Šƒ ‘–Š‡” ˆ‘”—Žƒ–‹‘• ‹ –‡”• ‘ˆ ͸ȋ͹ȌǣͳͲͶǦͳͳʹǡʹͲͳ͸Ǥ
†‹•‹–‡‰”ƒ–‹‘ –‹‡ ƒ† ”ƒ–‡ ‘ˆ †‹••‘Ž—–‹‘Ǥ   –Š‹• ͳ͹Ǥ Š‘–ƒ‹ǡ—–Šƒ”ǡŠƒŠǢ ‘”—Žƒ–‹‘ƒ†‡˜ƒŽ—ƒ–‹‘
ˆ‘”—Žƒ–‹‘†”—‰”‡Ž‡ƒ•‡‘ˆͻͻǤͺͶ™‹–Š‹ʹͷ‹™Š‹ Š™ƒ• ‘ˆˆƒ•–†‹••‘Ž˜‹‰–ƒ„Ž‡–•‘ˆ‘†ƒ•‡–”‘„›•‘Ž‹††‹•’‡”•‹‘‹
–Š‡Š‹‰Š‡•–‘ˆƒŽŽˆ‘”—Žƒ–‹‘• •—’‡”†‹•‹–‡‰”ƒ–•Ǥ Šƒ”ƒ ‡—–‹ ƒŽ ‡•‡ƒ” Šǡ Ͷʹȋ͵ȌǣͶͻǦͷͶǡ
 ʹͲͳ͵Ǥ
REFERENCES 
ͳǤ ƒ‰ƒŽǡŠƒ—” ǡƒ•ƒŽǤ ƒ•–†‹••‘Ž˜‹‰–ƒ„Ž‡–ǣƒ Acknowledgment
ƒ’’”‘ƒ Š ˆ‘” ‡‡”‰‡ › –”‡ƒ–‡–Ǥ –‡”ƒ–‹‘ƒŽ ‘—”ƒŽ ‘ˆ ‡ƒ”‡–Šƒˆ—Ž–‘‘—”’”‹ ‹’ƒŽ”Ǥƒ–‹Ž•‹”’”‘˜‹†‹‰–Š‡
‡•‡ƒ” Š‹›—”˜‡†ƒƒ†Šƒ”ƒ ›ǡ͵ȋ͵Ȍǣ͵͹͹Ǧ͵ͺͲǡʹͲͳʹǤ ˆƒ ‹Ž‹–‹‡•ƒ† ‘–‹—‘—•Ž›•—’’‘”– –‘ ƒ””›‘—––Š‹•‡•‡ƒ” Š
ʹǤ ‹‰Š  ǡ ƒ•‹Š ǡ —ƒ” Ǥ ƒ•– ‹••‘Ž˜‹‰ ƒ„Ž‡–•ǣ  ”‘‰”ƒ‡Ǥ Š‡ ƒ—–Š‘”• ƒ”‡ ƒŽ•‘ –Šƒˆ—Ž –‘ ”Ǥ ƒƒ”ƒ†
‡˜‹‡™Ǥ –‡”ƒ–‹‘ƒŽ ‘—”ƒŽ ‘ˆ —””‡– Šƒ”ƒ ‡—–‹ ƒŽ —Žƒ”‹ǡ  ‹‡–‹ˆ‹  ‹•–”—‡–ƒ–‹‘ ‡–”‡ǡ —›ƒ•ŠŽ‘
‡•‡ƒ” ŠǡͻȋʹȌǣͺǦͳͺǡʹͲͳ͹Ǥ Š‹Ž›ƒ†‡˜‹ ‘Žƒ”‘Žƒ’—”‹˜‡”•‹–›ǡ‘Žƒ’—”Ǥ
͵Ǥ ‹††‹“—‹  ǡ ƒ”‰ ǡ Šƒ”ƒ  Ǥ ƒ•– †‹••‘Ž˜‹‰ –ƒ„Ž‡–•ǣ 
’”‡’ƒ”ƒ–‹‘ǡ Šƒ”ƒ –‡”‹œƒ–‹‘ƒ†‡˜ƒŽ—ƒ–‹‘ǣƒ‘˜‡”˜‹‡™Ǥ – 
‘ˆŠ ‡˜ƒ†‡•ǡͶȋʹȌǣͺ͹Ǧͻ͸ǡʹͲͳͲǤ  Cite this article as:ƒ–‹Žǡ–—ŽŠƒ–ƒǡŠ”‹•Šƒ‹Ž
 Š—”‰Š—”‡ et alǤ ‘”—Žƒ–‹‘ ƒ† In-Vitro
ͶǤ ƒ˜‹‡•ǤŠƒ”ƒ ‘‹‡–‹ •‘ˆ‘•‡Ž–ƒ‹˜‹”ǣƒ‘”ƒŽƒ–‹˜‹”ƒŽ
 Šƒ”ƒ –‡”‹œƒ–‹‘ ‘ˆ •‡Ž–ƒ‹˜‹” ƒ•– ‹••‘Ž˜‹‰ ƒ„Ž‡–•
ˆ‘” –Š‡ –”‡ƒ–‡– ƒ† ’”‘’Š›Žƒš‹• ‘ˆ ‹ˆŽ—‡œƒ ‹ †‹˜‡”•‡
’‘’—Žƒ–‹‘•Ǥ ‘—”ƒŽ ‘ˆ –‹‹ ”‘„‹ƒŽ Š‡‘–Š‡”ƒ’›ǡ ʹȋͳȌǣͷǦ  •‹‰ —’‡” ‹•‹–‡‰”ƒ–•Ǥ ˜‡–‹ ƒ’‹†ǣ Šƒ” ‡ Šǡ
ͳͲǡʹͲͳͲǤ  ʹͲʹͲȋ͵ȌǣͳǦͳͳǡʹͲʹͲǤ
ͷǤ •™ƒ”‹›ƒ  ǡ —ƒ ǡ Š”‹•Šƒǡ ‘Œƒ Ǥ ‘”—Žƒ–‹‘ 
†‡˜‡Ž‘’‡– ƒ† ‡˜ƒŽ—ƒ–‹‘ ‘ˆ ‘•‡Ž–ƒ‹˜‹” ˆƒ•– †‹••‘Ž˜‹‰ 
–ƒ„Ž‡–• —•‹‰ •—’‡” †‹•‹–‡‰”ƒ–•Ǥ –‡”ƒ–‹‘ƒŽ ‘—”ƒŽ ‘ˆ
Šƒ”ƒ ›ƒ†Šƒ”ƒ ‡—–‹ ƒŽ‡•‡ƒ” Šǡ͸ȋͳȌǣʹ͵Ǧ͵ͲǡʹͲͳ͸Ǥ


˜‡–‹ƒ’‹†ǣŠƒ”‡ Š‘ŽǤʹͲʹͲǡ ••—‡͵ 11 ʹͲʹͲ’’–͵ͳͶͺʹ ̹ ˜‡–‹ ‘—”ƒŽ•ȋȌ–†


ȏ Ͳͻ͹͸Ǧ͵͹ͺ͵Ȑ —„Ž‹•Š‡†‘‡„ʹ͸ȀͲͶȀʹͲʹͲǡ™™™Ǥ‹˜‡–‹Ǥ‹

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