Co esponding au ho : Jadha Jayesh Gangadha
Copy igh © 2025 Au ho (s) e ain he copy igh o his a icle. This a icle is published unde he e ms o he C ea i e Commons A ibu ion License 4.0.
Mucoadhesi e buccal ilms o luna izine: o mula ion s a egies using β-
cyclodex in and polyme ic ca ie s: A e iew
Jayesh Gangadha Jadha 1, *, Sujal Anil Jagnade 1, Sahil Sonlal Janwale 1, P a ham Yogesh Banga 1, A ishka
Su esh Kad 1 and S. M. Bhaleka 2
1 Sama h Ins i u e o Pha macy, A ilia ed o D . Babasaheb Ambedka Technological Uni e si y (DBATU), Lone e,
Maha ash a, India.
2 Depa men o Quali y Assu ance, Sama h Ins i u e o Pha macy, A ilia ed o D . Babasaheb Ambedka Technological
Uni e si y (DBATU), Lone e, Maha ash a, India.
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 24(02), 011-017
Publica ion his o y: Recei ed on 20 Sep embe 2025; e ised on 01 No embe 2025; accep ed on 03 No embe 2025
A icle DOI: h ps://doi.o g/10.30574/wjbphs.2025.24.2.0978
Abs ac
Fluna izine dihyd ochlo ide, a calcium channel blocke used in he p ophylaxis o mig aine and es ibula diso de s,
su e s om poo aqueous solubili y and ex ensi e i s -pass me abolism, leading o low o al bioa ailabili y. To
o e come hese limi a ions, a mucoadhesi e hin ilm (MATF) o luna izine was de eloped using β-cyclodex in o
solubili y enhancemen and a ious polyme s such as HPMC E15, PVA, and Ca bopol 934P o ilm o ma ion and
mucoadhesion. The p epa ed ilm aims o achie e apid onse o ac ion, imp o ed solubili y, and be e pa ien
compliance. This pape e iews he o mula ion design, p epa a ion me hod, and e alua ion pa ame e s o he
de eloped ilm, highligh ing i s po en ial as a p omising al e na i e o con en ional dosage o ms.
Keywo ds: Fluna izine; Mucoadhesi e Thin Film; Β-Cyclodex in; Buccal Deli e y; Solubili y Enhancemen ; HPMC;
PVA; Ca bopol
1. In oduc ion
1.1. Mig aine
Mig aine ep esen s a ch onic neu ological condi ion cha ac e ized by ecu ing headache a acks ha a e ypically
pulsa ing in na u e and may be accompanied by nausea, omi ing, and pho ophobia/phonophobia. The headache is
ypically unila e al, esul ing om abe an b ain ac i i y wi h neu onal and ascula changes. T igeminal ac i a ion
leads o ascula changes ia he elease o neu opep ides, including CGRP and se o onin, which cause in lamma ion
and asodila ion ha unde lie he pain commonly expe ienced wi h mig aines.
Mig aine is equen ly igge ed by a a ie y o ac o s, such as s ess, changes in sleep pa e n, mens ual cycle, some
oods (cheese, chocola e, ca eine, ed wine), and en i onmen al ac o s such as b igh ligh o loud noise. App oxima ely
15–20% o he global popula ion sees some symp oms o mig aines, wi h emales mos o en showing symp oms.
Mig aine is a debili a ing diso de and a ec s quali y o li e.
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1.2. Fluna izine
Fluna izine is a selec i e calcium channel blocke ha is classi ied in he g oup o d ugs called cinna izine and is
p ima ily used o mig aine p ophylaxis. Fluna izine has an imig aine p ope ies due o he blockade o calcium en y
in o neu onal and ascula smoo h muscle cells, esul ing in dec eased ascula cons ic ion and neu onal exci abili y,
bo h o which con ibu e o he de elopmen o mig aine pain.
Fluna izine is also used o e igo and balance diso de s due o he an ihis aminic, seda i e, and es ibula supp essi e
e ec s. Howe e , he he apeu ic e icacy o luna izine is limi ed by i s poo wa e solubili y and low bioa ailabili y. To
amelio a e luna izine's physical limi a ions, mucoadhesi e hin ilm (MATF) o mula ions a e cu en ly being
de eloped. Ma o mula ions imp o e he solubili y, abso p ion, and onse o ac ions a e adminis a ion compa ed o
o al o mula ions.
1.3. Wha is MATF and I s Ad an ages
Mucoadhesi e Thin Films (MATF) ep esen an inno a i e app oach o d ug deli e y, acili a ing he expedi ed and
e ec i e abso p ion o he apeu ic agen s ac oss he o al mucosa. MATF can be desc ibed as hin ilms o shee s ha
possess lexible p ope ies and adhe en cha ac e is ics o he mucosal su aces (i.e., buccal o sublingual), allowing
d ugs o en e he sys emic ci cula ion while a oiding he i s -pass e ec .
• The ad an ages o MATF a e as ollows:
• Rapid onse o ac ion as a esul o apid d ug abso p ion h ough he mucosa;
• D ug abso p ion ha a oids he i s -pass me abolism leading o inc eased bioa ailabili y o poo ly soluble
d ugs;
• Ease o use wi hou he need o wa e making i ideal o pedia ic and ge ia ic pa ien s;
1.4. D ug P o ile o Fluna izine
Table 1 D ug P o ile Table
P ope y
Desc ip ion
Chemical Name
Fluna izine dihyd ochlo ide
Chemical S uc u e
Ca ego y
Calcium channel blocke
Molecula Fo mula
C26H26F2N2
Molecula Weigh
440.49 g/mol
Solubili y
Poo ly soluble in wa e , eely soluble in e hanol [15]
Bioa ailabili y
~40% due o i s -pass me abolism
Hal -li e
18–19 hou s
pKa
9.2
The apeu ic Uses
Mig aine p ophylaxis, e igo, es ibula diso de s
Mechanism
Blocks calcium en y in o smoo h muscle and neu onal cells
Limi a ion
Poo aqueous solubili y and a iable abso p ion
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2. Ra ionale o Mucoadhesi e Thin Film Fo mula ion
While luna izine is e ec i e in he p ophylaxis o mig aines, i s he apeu ic applica ion is hampe ed by poo aqueous
solubili y and poo o al bioa ailabili y, which can lead o a iable clinical ou comes, and esponse be ween pa ien s
[16]. Mucoadhesi e hin ilms (MATFs) p o ide an inno a i e solu ion by enabling di ec d ug deli e y o he buccal
mucosa, a oiding hepa ic i s -pass me abolism, and p o iding a as e and mo e eliable onse o ac ion [17,18]. The
addi ion o β-cyclodex in o ms inclusion complexes wi h luna izine, which inc eases solubili y, s abili y, and
dissolu ion a e. Fu he mo e, he use o syne gis ic polyme s, HPMC E15, PVA, and Ca bopol 934P, allows o adequa e
ilm o ma ion as well as unique mechanical s eng h, lexibili y, and mucoadhesion o emain in in ima e con ac wi h
a mucosal su ace while eleasing he d ug. Wi h his combina ion o enhanced solubili y and polyme enginee ing, he
MATF is a no el and pa ien -cen e ed al e na i e o con en ional o al dosage o ms, maximizing clinical ou comes and
minimizing a iabili y [19–21].
Figu e 1 Mucoadhesi e Thin Film Fo mula ion
3. Ma e ials and Me hods
3.1. Fo mula ion Composi ion
Table 2 Fo mula ion Table
Ing edien
Quan i y pe Film
Role
Fluna izine dihyd ochlo ide
10 mg
Ac i e d ug
β-Cyclodex in
30 mg
Solubili y enhance
HPMC E15
80 mg
Film- o ming polyme
PVA
40 mg
Film s eng h
Ca bopol 934P
20 mg
Mucoadhesi e agen
PEG 400
10% w/w
Plas icize
Ci ic acid
2 mg
Sali a s imula o
Aspa ame
3 mg
Swee ene
Dis illed wa e
q.s.
Sol en
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3.2. Reason o Selec ion o Ing edien s
• β-Cyclodex in: Used o enhance he solubili y and s abili y o he inco po a ed d ug h ough inclusion complex
o ma ion.
• HPMC E15: Se es as he p ima y ilm- o ming polyme , p o iding lexibili y, smoo h su ace, and uni o m ilm
hickness.
• Poly inyl Alcohol (PVA): Added o imp o e mechanical s eng h and ilm du abili y o easy handling and
applica ion.
• Ca bopol 934: Ac s as a mucoadhesi e polyme , ensu ing s ong adhesion o he buccal mucosa o p olonged
e en ion.
• P opylene Glycol: Func ions as a plas icize o enhance elas ici y, p e en b i leness, and imp o e ilm
lexibili y.
• Dis illed Wa e : Used as he sol en medium o dissol e and uni o mly dispe se all o mula ion ing edien s.
3.3. Me hod o P epa a ion
Fo ma ion o Inclusion Complex: Fluna izine and β-cyclodex in we e mixed in a mola a io o 1:3 by kneading me hod
o enhance he solubili y o Fluna izine and s abili y. The componen s we e blended wi h a small amoun o a wa e and
e hanol mix u e o gene a e a homogenous pas e and d ied a oom empe a u e.
P epa a ion o Polyme Solu ion: HPMC E15, PVA, and Ca bopol 934P we e accu a ely weighed and dissol ed in dis illed
wa e by s i ing un il uni o m wi h he p oduc ion o a polyme ic solu ion.
Inco po a ion o D ug Complex: The Fluna izine–β-cyclodex in inclusion complex was hen slowly scoped in o polyme
solu ion and app op ia e mixing was conduc ed ollowed by con inual s i ing o ensu e an e en dis ibu ion.
Addi ion o Excipien s: Plas icize (PEG 400) and swee ene (Aspa ame) will be added o he solu ion o imp o e
lexibili y o he ilm and i s pala abili y.
Cas ing and D ying: Finally, he solu ion we e pou ed on a le el glass pla e and sp ead e enly. The sol en was
e apo a ed a oom empe a u e and de eloped as a d y ilm ha was hin and lexible.
Cu ing and S o age: The ilm was d ied, peeled, and cu in o s ips o he same size. The ilms we e s o ed in a desicca o
un il es ing was pe o med.
4. E alua ion o Mucoadhesi e Thin Film
Mucoadhesi e hin ilms o luna izine a e ypically e alua ed o physicochemical and mechanical cha ac e is ics as a
measu e o quali y, s abili y, and accep abili y o he pa ien . S udies ha e examined he ollowing ypical e alua ion
pa ame e s and indings when e alua ing simila o mula ions [23-28].
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4.1. Thickness
Repo ed hicknesses gene ally ange om 0.18 - 0.22 mm., acili a ing epo able dis ibu ion o d ug wi hin ilm, and
consis en place dosing o he hin ilm.
4.2. Weigh Uni o mi y
Weigh o ilm was also uni o m, usually epo ed be ween 95 - 105 mg, demons a ing uni o m d ug loading and
ep oducible cas ing o ilms, app op ia e o each ilm.
4.3. Folding Endu ance
Repo ed olding endu ance a e gene ally epo ed abo e 250 olds, indica i e o app op ia e lexibili y wi h mechanical
s eng h o p e en c acking while being handled.
4.4. Su ace pH
Repo ed su ace pH anges om 6.2 - 6.8, indica ing app op ia e adjus men nea physiological pH o main ain a non-
i i an o buccal mucosa.
4.5. D ug Con en Uni o mi y
Values o d ug con en uni o mi y o mucoadhesi e ilms using HPLC analysis gene ally a e nea 97 - 102% o he
heo e ical alue, likely indica i e o physical homogenei y o d ug wi hin he polyme ma ix.
4.6. Swelling Index
Swelling index gene ally epo ed as 25-35%, su icien hyd a ion and a measu e o mucoadhesion o in ima e con ac
wi h he mucosal su ace.
5. Resul s
The published li e a u e on he de elopmen o mucoadhesi e hin ilms o Fluna izine con aining β-Cyclodex in and
a ious polyme s ha e consis en ly shown ha hese ilms a e a so , homogenous, and mechanically s able sys em.
Polyme componen s ypically used include he hyd oxyp opyl me hylcellulose (HPMC), poly inyl alcohol (PVA), and
Ca bopol, which when inco po a ed in o HPMC-PVA combina ion o mula ions imp o e lexibili y and inco po a ing
Ca bopol inc eases mucoadhesion. The addi ion o β-Cyclodex in has also been shown o imp o e he solubili y o
Fluna izine esul ing in a consis en d ug elease kine ics wi h sus ainable d ug elease. The ilms p oduced om
s udies gene ally show di usion-con olled d ug elease kine ics, ha e a neu ally anged pH, and hence a e non-
i i a ing o buccal mucosa. O e all, he published li e a u e sugges s hese o mula ions a e a iable al e na i e o
s anda d o al dosage o ms, while also p o iding o imp o ed bioa ailabili y and pa ien compliance c i e ia.
6. Discussion
Mucoadhesi e hin ilms o e dis inc bene i s o e con en ional o al dosage o ms by bypassing i s -pass me abolism
and enhancing d ug solubili y h ough cyclodex in complexa ion. The combina ion o HPMC E15, PVA, and Ca bopol
934P ensu es op imal s eng h, lexibili y, and adhesion, while PEG 400 and aspa ame imp o e ilm ex u e and
pala abili y. O e all, such o mula ions enhance d ug elease and main ain p olonged con ac wi h he buccal mucosa
o be e he apeu ic pe o mance.
7. Conclusion
The de elopmen o a mucoadhesi e hin ilm o Fluna izine using β-Cyclodex in and polyme s like HPMC, PVA, and
Ca bopol p o ides a p omising al e na i e o con en ional o al dosage o ms. The o mula ion o e s enhanced
solubili y, bypasses i s -pass me abolism, and imp o es pa ien compliance. Op imized polyme combina ions ensu e
adequa e mechanical p ope ies and mucoadhesion, while plas icize s and swee ene s imp o e lexibili y and
pala abili y. Such o mula ions can be conside ed o u he clinical e alua ion and po en ial comme cializa ion [31–
40].
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 24(02), 011-017
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Fu u e Di ec ions
The eme gence o mucoadhesi e hin ilm (MATF) echnology shows conside able p omise as an app oach o enhance
he deli e y o poo ly soluble and low-bioa ailabili y d ugs, such as luna izine. Fu u e s udies may be di ec ed owa d
he a ional selec ion and op imiza ion o polyme combina ions, unde s anding he inco po a ion o use o
nanoca ie s o achie e inc eased d ug loading, dissolu ion a e, and/o mucosal pe mea ion. O he po en ial u u e
di ec ions could include he de elopmen o sma ilms wi h s imuli- esponsi e o pH-sensi i e polyme s ha can
con ol and/o si e-speci ic d ug elease.
In he u u e, he e is an oppo uni y o MATF sys em o be explo ed o la ge-scale manu ac u ing and clinical
in es iga ion o es ablish hei sa e y, s abili y and pa ien compliance. The e is de ini e scope o addi ional s udies
ega ding MATF sys ems wi h combina ion he apy as well as mul ilaye bioadhesi e ilms which would ex end he
he apeu ic conside a ions o ch onic and neu ological diso de s. O e all, sys ems based on MATF hold g ea p omise
o be an al e na i e nex -gene a ion and pa ien iendly d ug deli e y pla o m.
Compliance wi h e hical s anda ds
Acknowledgmen s
The au ho s exp ess hei since e g a i ude o D . S. M. Bhaleka , Depa men o Pha maceu ical Quali y Assu ance,
Sama h Ins i u e o Pha macy, o his aluable guidance, mo i a ion, and con inuous suppo h oughou he
p epa a ion o his e iew pape . The au ho s also ex end hei app ecia ion o all he acul y membe s and s a o
Sama h Ins i u e o Pha macy o p o iding he necessa y acili ies and encou agemen o comple e his wo k
success ully.
Disclosu e o con lic o in e es
The au ho s decla e ha he e a e no con lic s o in e es ega ding he publica ion o his pape .
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