KATA PENGANTAR
Puji dan syukur kami panjatkan kehadirat keh adirat Tuhan Yang Yang Maha Esa, karena atas pimpinan dan rahmatNya, kami dapat menyelesaikan tugas makalah mata kuliah biofarmasi yang membahas tentang “ Rectal Drug Delivery System”. System”. . ami menyadari bah!a dalam penyusunan makalah ini masih jauh dari kata sempurna serta masih banyak kekurangan. "ntuk itu, kritik dan saran sangat dinantikan guna penyempurnaaan makalah ini dimasa mendatang. ami juga memohon maaf apabila dalam penulisan makalah ini terdapat kesalahan dan kekeliruan sehingga membingungkan pemba#a dalam memahami maksud kami. $emoga makalah ini dapat memberikan !a!asan dan pengetahuan serta bermanfaat bagi kami maupun pemba#a.
%akarta, No&ember '()*
Penyusun
1
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DAFTAR ISI KAT KA TA PENGANT PENGANTAR....................................................................................... AR....................................................................................... ........ .....1 DAFTAR ISI .................................................................................................................2 BAB I PENDAHULUAN .............................................................................................3
).)...........................................................................................................+atar elakang ..................................................................................................................................).'......................................................................................................umusan Masalah ................................................................................................................................../ ).-.........................................................................................................................Tujuan ................................................................................................................................../ BAB II TINJAUAN TINJAUAN PUSTAKA PUSTAKA ................................................ ................. ........ ......... 5
'.).0natomi dan 1isiologi e#tum ................................................................................* '.'.1ormulasi e#tal yang Tersedia ...............................................................................2 '.-.Masalah 1isiologis dan 1armasetik erkaitan dengan Penghantaran 3bat ektal..........................................................4 './.euntungan Penghantaran 3bat ektal..................................................... .............. ........ ......5 5 '.*.erugian Penghantaran 3bat ektal.......................................................................)( '.2 Mekanisme Pelepasan 3bat Melalui ektal............................................................)) '.6 0bsorpsi 3bat Melalui ektal.................................................................................)'.4 1aktor 7 faktor yang mempengaruhi 0bsorpsi ektal............................................)/ '.5 Pen#egahan Metabolisme +intas Pertama.............................................................)* '.)( arakteristik dan Pengaturan 0bsorpsi.................................................................)* '.)) 8at 9 :at Peningkat 0bsorpsi di ektal................................................... ..............)5 .......... ....)5 '.)' 8at Terapeutik Terapeutik yang ;iberikan ektal.................................................... .............. ........ ......'' '' BAB III PEMBAHASAN ..........................................................................................27 BAB IV PENUTUP.................................................................................................... 39
esimpulan...........................................................................................................-( $aran......................................................................................................................-)
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BAB I PENDAHULUAN
) .) .
+atar elakang ute per oral merupakan pemberian obat yang paling umum dalam penelitian dan
pengembangan obat baru dan bentuk sediaan, tetapi pemberian oral tidak selalu menghasilkan efek yang diinginkan atau dapat diterima oleh pasien. 3bat yang absorpsinya tidak baik di saluran gastrointestinal dan tidak stabil oleh en :im proteolitik merupakan beberapa masalah pada pemberian obat pada rute oral. eberapa obat men yebabkan iritasi lokal pada lambung atau saluran gastrointestinal atas atau membutuhkan dosis lebih dari *(( mg. Populasi pasien tertentu, umumnya anak7anak, orang tua dan pasien yang sulit menelan, seringnya kesulitan untuk mengonsumsi tablet dan kapsul oral. $ebagai tambahan, pengobatan beberapa penyakit paling baik dilakukan deng an pemberian langsung pada tempat yang sakit, umumnya pada penyakit di mata, mulut, dermal, rongga oral, dan jaringan anorektal. Pemberian oral dapat digunakan untuk tujuan drug targeted untuk jaringan yang terkena penyakit, namun terpaparnya seluruh kompartemen tubuh pada pemberian obat melalui oral tidak efisien dan bisa memi#u efek yang tidak diinginkan <anjita,$. amalinder,$. '()(=. Pemberian obat rektal dapat diterima baik untuk penghantaran obat lokal dan sistemik. Pemberian obat rektal efektif digunakan untuk mengobati penyakit lo#al pada area anorektal juga untuk menghasilkan efek sistemik sebagai alternatif dari pemberian oral. 3bat7obat yang mengalami metabolismee lintas pertama ketika diberikan oral, masalah ini dapat diatasi dengan pemberian obat tersebut melalui rute rektal. 1ormulasi penghantaran obat melalui rektal terdapat dalam berbagai bentuk sediaan, antara lain supositoria, gel, aerosol, busa < foam=, foam=, krim maupun controlled release. Meskipun release. Meskipun pemberian obat se#ara rektal tidak dapat menjadi rute pemberian yang umumnya diterima, penggunaan teknologi penghantaran obat
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) .' . a. b. #. d. e. ) .- . a. b. #. d. e.
umusan Ma Masalah agaimana agaimana mekanism mekanismee pelepasan pelepasan obat obat pada pada penghantara penghantaran n obat melalui melalui rektum> rektum> agaimana mekanisme absorpsi obat pada penghantaran obat melalui rektum> 1aktor7fak 1aktor7faktor tor apa saja yang yang mempengaru mempengaruhi hi absorpsi absorpsi obat di di rektum> rektum> agaimana agaimana modifika modifikasi si dan dan optimasi optimasi absorpsi absorpsi obat di rektum> rektum> 0pa saja saja #ontoh #ontoh produk obat rektal rektal yang beredar beredar di pasaran pasaran > Tujuan Mahasis!a Mahasis!a memahami memahami mekanis mekanisme me pelepasan pelepasan obat obat pada penghant penghantaran aran obat obat melalui melalui rektum Mahasis!a memahami mekanisme absorpsi obat pada penghantaran obat melalui rektum Mahasis!a Mahasis!a memahami memahami faktor faktor7fak 7faktor tor yang yang mempengaruhi mempengaruhi absorpsi absorpsi di rektum Mahasis!a Mahasis!a memahami memahami metode metode modifik modifikasi asi dan optimasi optimasi absorpsi absorpsi di rektum rektum Mahasis!a Mahasis!a memahami memahami mekanis mekanisme me pelepasan pelepasan dan dan absorpsi absorpsi dari dari bentuk bentuk sediaan sediaan penghantaran obat rektal yang beredar di pasaran
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'.). '.).
0nat 0natom omii 1isi 1isiol olog ogii ekt ektum um Panjang rektum kira7kira )* #m, berakhir di anus. Tanpa adanya bahan fekal, rektum
mempunyai sejumlah ke#il #airan
Aambar ). 0natomi Pembuluh ;arah di ektum, )B &ena tengah rektalC ' B tuni#a mus#ularis B stratum longitudinalC -B otot le&ator aniC /B &ena inferior rektalC * B otot sfingter ani eDternusC 2 B &ena superior rektalC 6 dan 4 B pleDus &enosus rektalis
ektum berfungsi sebagai tempat penyimpanan sementara feses. iasanya rektum ini kosong karena tinja disimpan di tempat yang lebih tinggi, yaitu pada kolon desendens. %ika
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defekasi. %ika defekasi tidak terjadi, sering kali material akan d ikembalikan ke usus besar, di mana penyerapan air akan kembali dilakukan. %ika defekasi tidak terjadi untuk periode yang lama, konstipasi dan pengerasan feses akan terjadi '.'. '.'.
1orm 1ormul ulas asii ek ekta tall yang yang Tersed rsedia ia
a. $upo $uposi sito tori riaa Pad Padat at $upositoria padat merupakan bentuk sediaan yang paling umum digunakan untuk pemberian obat rektal dan lebih dari 54 bentuk sediaan rektal berada dalam bentuk supositoria. "mumnya bentuk sediaan ini berbentuk torpedo yang terdiri dari basis lemak atau basis larut air yang beratnya ber&ariasi dari ) g
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pada saluran rektal mengurangi masalah kepatuhan pasien. Pelepasan obat dengan bentuk sediaan semisolid biasanya terbatas untuk indikasi lokal seperti hemorrhoid dan radang perut ba!ah
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memberikan manfaat yang signifikan. 1aktor yang membatasi adalah kebutuhan untuk menginkoporasikan :at pengontrol yang diran#ang untuk mengatur pelepasan obat yang se#ara sgnifikan akan meningkatkan ukuran total dari bentuk sediaan. entuk sediaan untuk orang de!asa yang dapat diterima adalah sampai ',* g, jumlah obat yang bisa diformulasi dalam bentuk sediaan pelepasan terkontrol bisa '7- kali lebih besar dari formulasi oral. "ntuk beberapa :at terapeutik, jumlah obat yang lebih tinggi ini memberikaan keuntungan yang tidak diperoleh le!at rute oral.. Pengembangan dan pemasaran bentuk sediaan rektal pelepasan terkontrol masih belum menguntungkan karena masih enggannya pasien untuk menggunakan rute ini dan masalah kepatuhan pasien. '.-. '.-. Masala Masalah h 1isiol 1isiologi ogiss dan 1armas 1armaseti etik k erkai erkaitan tan deng dengan an Pengha Penghanta ntaran ran 3bat 3bat ekt ektal al a. Pert Pertim imba bang ngan an 0nat 0natom omii ektu ektum m Tidak seperti usus halus dan kolon bagian atas kolon, pembuluh darah yang terdapat pada saluran rektal tidak seluruhnya langsung menuju suplai darah ke hati. @ena hemorrhoidal ba!ah dan tengah dari bypass rektum, merupakan sirkulasi portal selama lintas pertama menuju menuju sirkulasi umum, mengi:inkan obat yang diserap mendesak efek sistemik disebabkan oleh metabolisme dan ekskresi &ia mekanisme hepatik. $aluran rektal juga dikosongkan oleh sirkulasi limfatik yang luas yang memfasilitasi absorpsi dan paparan sistemik dari obat yang terserap. Ja Jalaupun laupun &illi dan mikro&illi tidak terdapat pada jaringan rektum dan kolon, luas permukaan yang men#ukupi mengi:inkan absorpsi dari obat yang permeable. urangnya motilitas pada rektum dan kolon, menyediakan keuntungan tambahan untuk mempertahankan gradient konsentrasi yang maksimal pada permukaan absorpsi. ersamaan dengan terbatasnya &olume #airan
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metaboli# intraselular sama pada sel epitel. Perbedaan utama pada metabolisme obat terjadi pada en:im7en:im dimana obat terpapar pada lumen usus dan membran api#al dari lapisan sel epitel. arena kolon dan rektum tidak memiliki fungsi #erna, tidak terdapat en:im lumen, yang se#ara aktif diekskresikan oleh usus halus bagian atas. $ehingga, obat yang tidak stabil oleh en:im proteolitik seperti peptida dan protein memiliki stabilitas yang lebih besar jika dilepaskan pada rektum atau kolon bagian ba!ah. Penelitian yang dilakukan $affran et al. menunjukkan bah!a &asopressin, peptida yang menjadi subyek hidrolisis proteolitik, lebih aktif ketika diberikan melalui rute rektal dibandingkan rute oral. 0bsorpsi rektal yang signifikan pada hormon pertumbuhan dan insulin juga ditunjukkan dengan bantuan :at peningkat absorpsi. Pemba!a untuk &itamin juga terdapat pada jaringan usus halus. Pemba!a ini tidak terdapat pada mekanisme transport di jaringan kolon dan rektal sehingga senya!a seperti asam amino, sakarida dan &itamin dan senya!a lain yang memiliki struktur yang mirip dan membutuhkan pemba!a untuk absorpsinya mengurangi absorpsinya di rektal. p? pada kompartemen rektal umumnya netral, antara 6 sampai 4, dengan kapasitas dapar yang minimal jika dibandingkan dengan usus halus. $upositoria atau larutan diformulasi untuk mempertahankan p? spesifik yang bertujuan untuk mengoptimalksan absorpsi obat pada p? tersebut. ?al ini menguntungkan untuk obat yang sifat permeasinya optimal pada p? mendekati netral. ?al yang perlu diingat adalah untuk menjaga p? permukaan membrane epitel, pada rentang p? 2,(72,*. './. './. eun euntu tung ngan an Pen Pengh ghan anta tara ran n 3bat 3bat ekt ektal al a. entuk sediaan sediaan relatif relatif besar dapat ditampung ditampung dalam dalam rektum rektum b. ute rektal aman dan nyaman bagi pasien usia lanjut dan muda Pengen#e bat dimini diminimalkan malkan karena &olume &olume #air sidu rendah
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Pemberian supositoria yang kurang nyaman bagi pasien menurunkan kepatuhan pasien. b. Potensi untuk hilangnya obat $etidaknya ada dua masalah umum yang dapat menyebabkan hilangnya obat pada pemberian rektal. Pertama, untuk absorpsi yang efektif, sediaan harus tertahan dalam rektum, sehingga jika sediaan atau bagiannya hilang dari rektum, absorpsi obat akan menurun. edua, terdapat kemungkinan obat atau beberapa eksipien penting berinteraksi dengan isi rektum seperti feses atau #airan rektum. ?al ini dapat menurunkan absorpsi obat dan mengurangi keefektifan obat. #. Terba Terbatas tasnya nya #airan #airan dalam dalam rekt rektum um %umlah #airan rektum sekitar - ml, jumlah yang ke#il jika dibandingkan dengan jumlah #airan di saluran gastrointestinal g astrointestinal ketika obat diberikan se#ara oral. @o @olume #airan yang sedikit tersebut dapat membatasi pelarutan obat, khususnya yang memiliki kelarutan dalam air yang rendah. ?al ini juga menjadi masalah apabila pelarutan pemba!a merupakan rate determining step pada step pada pelepasan obat dari pemba!a. d. 1ormulasi Terdapat begitu banyak &ariabel dan pertimbangan formulasi yang dapat menyebabkan kesulitan dalama absorpsi obat melalui rektal, termasuk pelelehan dan sifat pen#airan pemba!a. elarutan obat dalam pemba!a, ukuran partikel obat, kapasitas penyebaran pemba!a, &iskositas pemba!a dan eksipien pada suhu rektum, dan kemungkinan retensi obat oleh eksipien, semua itu dapat mempengaruhi ke#epatan pelepasan dan selanjutnya absorpsi obat. +ebih jauh lagi, pa obat, p? #airan rektum, adanya adan ya dapar, dan kapasitas dapar pada #airan rektum juga koefisien partisi dari obat mempengaruhi absorpsi obat dan harus dipertimbangkan saat memformulasi supositoria atau bentuk sediaan rektal yang lain. $uhu penyimpanan, !aktu dan kondisi penyimpanan ditemukan memberikan
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diabsorpsi dalam 'I- bagian ba!ah rektum langsung men#apai &ena #a&a inferior dan tidak melalui &ena porta. euntungan pemberian melalui rektal
Aambar '. Mekanisme Pelepasan 8at 0ktif dari asis $upositoria <0ulton, '((6=
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Penyerapan hanya terjadi pada pembuluh darah se#ara langsung le!at inferior dan &ena intermedier yang berperan dan memba!a :at aktif melalui &ena ilia#a ke &ena #a&a inferior. Menurut Lue#au&iller dan %und bah!a penyerapan dimulai dari &ena haemorrhoidalles inferior terutama &ena haemorrhoidalles superior menuju &ena porta melalui &ena mesentri#um inferior. $aluran getah bening juga berperan pada penyerapan rektal yaitu melalui saluran toraks yang men#apai &ena sub#la&ula sinistra. Menurut 1abre dan egnier pengaruh tersebut hanya berlaku pada obat7obat yang larut lemak. Mukosa rektum dalam keadaan tertentu bersifat permeabel sempurna. Penyerapan rektum kadang7kadang lebih baik dari penyerapan bukal. $elain itu penyerapan juga tergantung pada derajat pengosongan saluran #erna jadi tidak dapat diberlakukan se#ara umum. ahkan beberapa obat tertentu tidak diserap oleh mukosa rektum. anyak obat yang tidak diresorbsi se#ara teratur dan lengkap dari rektum, sebaiknya diberikan dosis yang melebihi dosis oral dan digunakan pada rektum kososng, akan tetapi setelah obat diresorbsi efek sistemisnya lebih #epat dan lebih kuat dibandingkan per oral, berhubung &ena7&ena ba!ah dan tengah dari rektum tidak tersambung pada sistem porta dan obat tidak melalui hati pada peredaran peredara n darah pertama, sehingga tidak mengalami perombakan 1PE < first first pass effect =. =. Penge#ualian
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portal dan akan mengalami metabolisme lintas pertama di hati. $atu7satunya #ara menghindari metabolisme lintas pertama adalah memberikan obat pada bagian ba!ah rektum. 0bsorpsi obat melalui epitel rektal melibatkan dua rute transport yaitu rute transelular dan rute paraselular. Mekanisme pengambilan pada rute transelular bergantung pada lipofilisitas sedangkan rute paraselular adalah difusi obat melalui ruang antara sel7sel epithelial. 0bsorpsi 0bsorpsi rektal dari obat bergantung pada beberapa sifat obat seperti koefisien partisi dan ukuran mole#ular. oefisien oefisien partisi yang ke#il, ukuran mole#ular yang besar, muatan dan kemampuan pembentukan ikatan hydrogen yang tinggi adalah faktor7faktor yang menyebabkan absorpsi yang rendah dari obat. 1aktor lainnya adalah adanya feses yang bisa mengubah absorpsi obat. +arutan, suspensi dan supositoria merupakan bentuk sediaan yang umum untuk pemberian rektal. andungan rektal umumnya bersifat basa dan larutan basa biasanya #epat diserap dibandingkan larutan yang bersifat asam. +arutan berair dan alkohol diserap dengan #epat sedangkan suspensi dan supositoria absorpsinya lambat dan kontinyu. Metode utama yang digunakan untuk memperbaiki absorpsi rektal dari obat termasuk B Modifikasi formulasi untuk memperbaiki tahap pelarutan dari obat7obat yang •
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mempermudah absorpsi tergantung pada konsentrasi dan interaksi obat yang mungkin terjadi. "kuran partikel obat se#ara langsung berhubungan dengan laju absorpsi. oefisien partisi, ukuran molekular, muatan
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obat bisa diserap dengan d engan efisien dari rektum. @oigt @oigt dan 1alk melaporkan hubungan langsung antara kelarutan dalam air dengan ke#epatan pelepasan untuk -* senya!a yang berbeda. "mumnya, ketika senya!a berada dalam bentuk kelarutan yang relati&e rendah
air. "kuran molekular $emakin ke#il ukuran molekul obat, semakin siap atau #epat obat tersebut diabsorpsi. "ntuk molekul7molekul yang besar, beberapa tipe transport terfasilitasi atau
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ketersediaan obat. ;i sisi lain, adsorpsi atau pembentukan kompleks dengan surfaktan •
dapat menurunkan ketersediaan obat an absorpsinya. Penyebaran formula yang diberikan "ntuk absorpsi obat yang optimal, merupakan hal yang penting untuk supositoria atau pemba!a meleleh atau melarut dengan #epat dan tersebar pada seluruh dinding rektum. 3leh karena itu sifat rheologik dari pemba!a dapat memberikan efek yang signifikan pada pelepasan obat dan kemampuan obat untuk kontak dengan mukosa rektal. eberapa studi menganjurkan &iskositas pemba!a merupakan hal yang sangat penting untuk pelepasan obat dari pemba!a. Jalaupun Jalaupun sifat sebar menentukan se#ara langsung area dimana pelepasan dari pemba!a terjadi dan kemudian absorpsi, terdapat juga kesulitan bah!a konsentrasi dan ak ti&itas termodinamika obat bisa menurun jika tersebar terlalu banyak dan tersebar sampai bagian atas rektum. ?al ini dapat menyebabkan absorpsi pada &ena hemorrhoidal atas dan menuju ke sirkulasi
•
darah dan meningkatkan metabolisme lintas pertama. 3ptimalisasi 0bsorpsi 3bat 7 Enhancing agents <8at agents <8at Peningkat= +ebih dari '( tahun, berbagai :at telah diidentifikasi se#ara signifikan
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merupakan kondisi ideal. %ika diberikan se#ara oral, :at peningkat absorpsi kurang efektif dibandingkan dengan diberikan rektal, hal ini disebabkan karena motilitas yang tinggi dan pengen#eran obat dan enhancer. Penentuan ran#angan dan kinerja dari supositoria solid rektal harus memiliki profil pelepasan dari kedua :at tersebut
formulasi. ontrol p? p? #airan rektal memiliki efek yang penting dalam absorpsi obat dari rektum. arena #airan rektal memiliki kapasitas dapar yang relati&e rendah dan &olume #airan rektal yang ke#il, dapat diperkirakan bah!a kandungan bentuk
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!aktu yang singkat. "ntuk basis yang berminyak, solubilisasi, dengan pengurangan &iskositas pemba!a, dapat memperbaiki penghantaran obat rektal 7 iscosity modifiers Tekanan lumen pada mukosa rektal bisa bekerja sebagai shearing sebagai shearing stress stress dan dan mempengaruhi sifat rheologis dari :at yang memiliki sifat plastik atau pseudoplastis. @iskositas @iskositas merupakan hal yang sangat penting untuk pelepasan obat dari supositoria ketika bahan yang meleleh merupakan #airan Ne!tonian. "mumnya, semakin rendah &iskositas, semakin #epat dan semakin sempurna pelepasan obat dari pemba!a dan semakin tinggi absorpsi obat. '.)). 8at7:at Peningkat 0bsorpsi di ektum
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serum diamati setelah pemberian kedua supositoria enamin. ?asilnya adalah periode !aktu selama enamin meningkatkan absorpsi rektal insulin sangat pendek. $tudi detail mengenai mekanisme untuk kerja enamin sebagai bahan tambahan belum dilaporkan. Enamin bisa meningkatkan absorpsi rektal dari senya!a dengan bobot molekul yang relati&e besar seperti insulin bahkan kerjanya lebih kuat pada obat yang bobot molekulnya relati&e ke#il. Perhatian utama untuk turunan enamin dalam penggunaannya untuk pengembangan formulasi adalah stabilitas enamin sendiri. Pada banyak kasus, enamin bisa mengalami hidrolisis yang sangat #epat pad a nilai p? netral atau lebih •
rendah dan pada basis supositoria yang mengandung lembap. $alisilat dan turunannya
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dapat memodifikasi fungsi permukaan sel yang disebabkan oleh pengikatan aresena:o HHH danIatau inakti&asi #almodulin dengan menurunkan konsentrasi Ga' pada sitosol. $alisilat terutama diangkut melalui sel7sel epitel pada konsentrasi rendah, namun salisilat dalam konsentrasi tinggi diangkut le!at rute interselular yang di#apai pada dosis terapeutik. $alisilat dan *M$0 menghambat metabolisme dari laktat menjadi piru&at pada siklus TG0. 3leh karena itu, pemberian salisilat atau atau *M$0 dengan insulin dalam supositoria bisa memi#u efek terapeutik sinergis demikian juga dengan efek peningkat absorpsi. $alisilat dan *M$0 merupakan adju&ant yang aman yang telah d ibuktikan •
melalui studi sitologi. 0sam7asam lemak
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$ebelum ini satu7satunya metode yang tersedia untuk memperoleh efek terapi segera dari obat antikon&ulsan untuk epilepsi h anya melalui rute intra&ena. Namun pemberian intra&ena memiliki beberapa masalah teknis dalam pemberiannya sehingga bentuk sediaan rektal menjadi alternatif rute pemberian obat. ;ia:epam sangat #epat diserap dari larutan yang diberikan rektal dalam pemba!a propilenglikol7air7etanol pada sukarela!an sehat. 1ormulasi supositoria dia:epam efektif dan aman untuk pen#egahan kejang pada anak7anak sehingga formulasi dengan pelepasan yang tidak segera bisa digunakan untuk terapi profilaksis. p rofilaksis. Pada pasien epilepsi de!asa, )( mg dia:epam dalam ' ml larutan intra&ena diberikan se#ara rektal dan konsentras obat dalam serum sebanding dengan pemberian p emberian oral dari tablet )( mg. ioa&ailabilitas
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Pemberian oral analgesik narkotik untuk pengobatan paska operasi dan nyeri pada kanker sering menyebabkan mual dan muntah atau kondisi pasien yang buruk. eberapa penelitian mengindikasikan bah!a morfin yang diberikan rektal memiliki
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bioa&ailabilitas absolute sempurna. euntungan lain dari pemberian metoklorpramid se#ara rektal adalah tidak terjadinya metabolisme lintas pertama. *= 8at 8at 0nt 0ntib ibak akte teri ri Metronida:ol digunakan luas untuk profilaksis dan pengo batan infeksi bakteri
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dilepaskan melalui mekanisme difusi ;isolusi B
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ke#epatan pelepasan obat. 0bsorpsi B 0tenolol diabsorpsi pada
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$upositoria dalam bentuk #air harus memiliki kekuatan g el yang sesuai sehingga tidak bo#or atau keluar dari anus setelah pemberian. PoloDamer memiliki gaya mukoadhesif yang lebih besar terhadap membrane mukosa rektal dibandingkan hidroksietilselulosa. ?al ini
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