Peningkatan Disolusi Nifedipin dari Mikrokristalnya yang Dibuat Melalui Pengendapan Antisolvent dengan Keberadaan Poloxamer 188 atau Natrium Lauril Sulfat

Penelitian ini bertujuan untuk meningkatkan laju disolusi nifedipin melalui pembentukan mikrokristalnya. Mikrokristal nifedipin dibuat melalui pengendapan antisolvent dengan keberadaan poloxamer 188 atau natrium lauril sulfat pada tiga konsentrasi (1%, 3%, dan 5%) sebagai stabilisator dan peningkatan keterbasahan. Karakterisasi mikrokristal yang dilakukan meliputi morfologi, spektrofotometer inframerah, difraksi sinar-X dan uji disolusi. Profil disolusi nifedipin dari mikrokristalnya menunjukkan peningkatan dibandingkan dengan serbuk nifedipin. Kecepatan disolusi terbaik nifedipin dari mikrokristalnya dengan keberadaan NLS adalah mikrokristal nifedipin-natrium lauril sulfat 5% sedangkan untuk profil disolusi nifedipin dari mikrokristalnya dengan keberadaan poloxamer 188 dalam berbagai konsentrasi tidak berbeda secara bermakna. Profil disolusi nifedipin terbaik dari mikrokristal nifedipin-natrium lauril sulfat dan poloxamer 188 tidak berbeda secara bermakna. Campuran fisik serbuk nifedipin-surfaktan dengan perbandingan 9:1 memberikan profil disolusi lebih baik dari mikrokristalnya. Hasil pengamatan mikrokristal melalui SEM tidak menunjukkan perbedaan morfologi kristal. Sementara hasil pemeriksaan serapan inframerah, difraksi sinar X memberikan parameter yang sama. Perbedaan kecepatan disolusi nifedipin dari serbuk nifedipin, mikrokristal, dan campuran fisik bukan disebabkan oleh perbedaan bentuk kristal (polimorfisme) tetapi karena adanya perbedaan ukuran partikel dan keberadaan surfaktan.Kata Kunci: nifedipin, poloxamer 188, natrium lauril sulfat, disolusi, pengendapan antisolvent, mikrokristal. The aim of this study is to enhance the dissolution rate of nifedipine through formation its microcrystal. Microcrystals of nifedipine are made by antisolvent precipitation with presence poloxamer 188 (PLX) and sodium lauryl sulfate (SLS) within three concentrations (1%, 3%, 5%) as stabilitator and wet improver. Then, the crystal characterization will be carried out through crystal morphology, infrared spectrum, x-ray diffraction pattern, and dissolution test. Dissolution rate profile of nifedipine from microcrystal showed enhancement was comapared by nifedipine powder. The best dissolution rate profile of nifedipine from microcrystal with presence of SLS is nifedipine microcrystal-SLS 5% whereas for dissolution rate profiles of nifedipine from microcrystal with presence of PLX within some concentration were not different significantly. Dissolution rate of nifedipine from microcrystal-SLS 5% was not different significantly with dissolution rate profiles of nifedipin from microcrystal with presence of PLX. Physical mixture of nifedipine powder-surfactant showed dissolution rate profiles better than its microcrystal. The crystal morphology which observed by SEM did not showed differences. The characterization with infrared spectrophotometer, X-ray diffraction showed the same result for all sample. The difference of dissolution rate of nifedipine was not caused by the shape of its crystal (polymorphism) but by the difference of particle size and presence of surfactant.Keyword: nifedipine, poloxamer 188, sodium lauryl sulfate, dissolution, antisolvent precipitation, microcrystal

Pembuatan dan Karakterisasi Dispersi Padat Sistem Biner dan Terner dari Gliklazid

Gliklazid adalah obat yang mempunyai kelarutan rendah dan permeabilitas tinggi (BCS II). Teknik dispersi padat telah dikembangkan secara luas untuk meningkatkan laju disolusi obat yang mempunyai kelarutan rendah. Tujuan dari penelitian ini adalah meningkatkan laju disolusi gliklazid dengan teknik dispersi padat dengan pembawa poloxamer 188, HPMC, dan Eudragit® E100. Dispersi padat pada penelitian ini dibuat dengan metode pelarutan. Dispersi padat gliklazid dalam sistem biner dengan poloxamer188 dibuat dalam perbandingan ; 1:0,5, 1:0,75, 1:1, 1:1,5 dan 1:2, dengan HPMC dibuat dalam perbandingan 1:0,1, 1:0,125, dan 1:0,25 sedangkan dengan Eudragit® E100 1:0,25. Dispersi padat sistem terner dibuat perbandingan gliklazid-poloxamer188-HPMC 1:2:0,1 dan 1:2:0,25, sedangkan gliklazid-poloxamer188- Eudragit® E100 pada perbandingan 1:2:0,1 dan 1:2:0,25. Karakterisasi dilakukan dengan uji disolusi, DSC, FTIR, dan XRD. Pada menit ke-15, laju disolusi terbesar dari dispersi padat sistem biner dan terner diperolah dari gliklazid-poloxamer188 1:2 dan gliklazidpoloxamer188-Eudragit® E100 1:2:0,25 yang memberikan peningkatan laju disolusi 12 kali dan 15 kali lebih besar dibanding gliklazid murni. Penurunan puncak endotermik dari gliklazid dalam dispersi padat dengan DSC dan penurunan intensitas pola difraksi gliklazid menunjukkan terjadinya penurunan derajat kristalinitas. Karakterisasi dengan FTIR menunjukkan hampir tidak ada pergeseran puncak serapan gugus fungsi gliklazid pada dispersi padat.Kata kunci: disolusi, gliklazid, dispersi padat, poloxamer 188, HPMC, Eudragit® E100 Gliclazide is a drug with poor water solubility and high permeability. Solid dispersion technique is widely used to improve the dissolution rate of the drug with poor solubility. This study aims to improve the dissolution rate of gliclazide by solid dispersion technique with poloxamer 188, HPMC, and Eudragit® E100 as carriers. Solid dispersions were prepared by solvent evaporation methods in binary and ternary system. In binary system gliklazid was mixed with poloxamer188 in the ratio of 1:0.5, 1:0.75, 1:1, 1:1.5 and 1:2, with HPMC in the ratio of 1:0.1, 1:0.125, and 1:0.25, and with Eudragit® E100 in 1:0.25 ratio. In ternary system gliclazide were prepared with poloxamer188 and HPMC in the ratio of 1:2:0.1 and 1:2:0.25, and with poloxamer188 and Eudragit® E100 in the ratio of 1:1:0.25 and 1:2:0.25. Pure gliclazide, solid dispersions and physical mixtures were characterized by dissolution testing, DSC, FTIR, dan XRD. At the 15th minute, the highest dissolution rate observed from binary and ternary solid dispersions of gliclazide were from gliclazide-poloxamer188 1:2 dan gliclazidepoloxamer188 and Eudragit® E100 1:2:0,25 which showed 12 and 15 fold increase in dissolution rate compared by pure gliclazide. The decrease of endothermic peak (DSC) and the intensity of the diffraction pattern by XRD of solid dispersions showed the decrease of crystallinity rate. Characterization by FTIR virtually showed no shift of absorption peaks of gliclazide on solid dispersion.Keywords: dissolution, gliclazide, solid dispersions, poloxamer 188, HPMC, Eudragit® E10

FORMULATION OF POLYMER-NANO COMPOSITE FILM FOR COATING GRASTRORETENTIVE TABLET OF DIPYRIDAMOL AS A MODEL

Objective: The aim of this work was to formulate the polymer nano composite film to coat the gastroretentive tablet.Methods: The polymer nano composite film was formulated by varying the concentration of Eudragit® RS/RL 30D, PEG 6000 and with or without sodium bentonite. The polymer nano composite was then used to coat the gastroretentive dipyridamol tablet as a model.Results: The film containing Eudragit® RS/RL 30D at ratio 80:20 with 20 % PEG 6000 (w/w dry polymer) and 2% sodium bentonite (w/w dry clay) (formulation 16) was more elastic and strength. The diffusion test showed that the percentage of dipyridamole passed through the film of formulation 8 (without sodium bentonite) and 16 was superimposed during the 7 first hours and after 7 hours, they split in which the formulation 8 was higher than formulation 16. The floating lag time and capacity of the coated tablet with nano composite were 1': 53†and more than 8 hours, respectively, while for tablet coated without nano composite were 0': 09†and 7': 08': 27†respectively. The release showed that the gastroretentive dipyridamol tablet coated by polymer nano composite (formulation 16) released dipyridamol 43.59±3.59 and 89.69±4.92% at 4th and 8th hour respectively, while the tablet coated without nano composite (formulation 8) released 44.76±4. 74% and 95.76±1.35% respectively.Conclusions: The polymer nano composite film containing Eudragit® RS/RL 30D with the ratio of 80:20 and 20% PEG 6000 (w/w dry polymer) with the presence of 2% sodium bentonite generated tablet that floated for 8 hours and produced the release of the drug according to the requirement that has been set.Â

Formulation of Dipyridamole Sustained Release Tablet Using Floating System

Dipyridamole is a drug for prevention of postoperative thromboembolic complication of heart valve replacement and long term therapy of angina pectoris will be well absorbed in stomach. To maintain therapeutic plasma concentration in long time and to increase bioavalaibility is needed a sustained release dosage form having the long residence time in the stomach. The objective of this research was to make floating sustained release tablet of dipyridamole conforming to the requirement that was set up by dipyridamol therapeutic concentration. Tablets were made by wet granulation method using aquadest as a liquid binder, HPMC K4M, Ac-di-sol, Avicel PH 102, talk, and Mg stearat. Dissolution assay was carried out using type 2 release tester at rotation speed of 50 rpm in medium 900 mL HCl 0.1 N at 37 ± 0.5 °C for 8 hours. The formulation containing of 50 mg dipirydamole, HPMC K4M (30%), Ac-di-sol (20%), Avicel PH 102 (37%), talk (2%), and Mg stearat (1%) released 59.61 ± 6.73% and 89.34 ± 5.87% of dipyridamole respectively after 4 and 8 hours that conformed to the requirement

Freeze drying and calcining hydrotalcite for improving acid neutralizing capacity

Acid  neutralizing  capacity  (ANC)  is  one  of  the  important  factor  on effectivity  determination  of  antacid  dosage  forms.  Antacid dosage forms have different values depend on their ANC.  The objective of this research was to modified physical and chemical properties of hydrotalcite which can increase its acid neutralization capacity.  Hydrotalcite was treated by freeze drying and calcination at different temperature 100, 200, 300, and 500°C. This hydrotalcite was characterized by X-Ray Diffractometer  (XRD)  and  Scanning  Electron Microscope (SEM); and was determined acid neutralization capacity. The results showed  that  acid  neutralization  capacity  of  hydrotalcite  increased  after  it  was freeze  dried and  calcined  at  200,  300  and  500  °C.  The  result  of  XRD  for  the hydrotalcite  calcined  at  200  °C  have  showed  the  lower  intensity  of  peaks, whereas the calcination at 300 and 500 °C were disappeared and appeared new peaks at different 2θ.Key words: Acid neutralization capacity, hydrotalcite, calcination, XRD, SE

PREPARATION AND CHARACTERIZATION OF GLICLAZIDE SOLID DISPERSION IN BINARY AND TERNARY SYSTEM

Objective: The objective of this research was to improve the dissolution rate of gliclazide by solid dispersion technique with poloxamer 188, HPMC, and Eudragit® E100 as carriers.Methods: Solid dispersions were prepared by solvent evaporation methods in the binary and ternary system. In binary system gliclazide was mixed with poloxamer188 in the ratio of 1:0.5, 1:0.75, 1:1, 1:1.5 and 1:2, with HPMC in the ratio of 1:0.1, 1:0.125, and 1:0.25, and with Eudragit® E100 in 1:0.25 ratio. In ternary system gliclazide was prepared with poloxamer188 and HPMC in the ratio of 1:2:0.1 and 1:2:0.25, and with poloxamer188 and Eudragit® E100 in the ratio of 1:1:0.25 and 1:2:0.25. Pure gliclazide, solid dispersions, and physical mixtures were characterized by dissolution testing, DSC, FTIR, dan XRD.Results: At the 15th minute, the highest dissolution rate observed from binary and ternary solid dispersions of gliclazide were from gliclazide-poloxamer188 1:2 dan gliclazide-poloxamer188 and Eudragit® E100 1:2:0,25 which showed 12 and 15 fold increase in dissolution rate compared by pure gliclazide. The decrease of endothermic peak (DSC) and the intensity of the diffraction pattern by XRD of solid dispersions showed the decrease of crystallinity rate. Characterization by FTIR virtually showed no shift of absorption peaks of gliclazide on solid dispersion.Conclusion: The results of this study indicate that the solid dispersion of gliclazide using poloxamer and Eudragit®E100 in 1:2:0, 25 ratio of weight was the best in enhancing the dissolutions characteristics and bioavailability

Formulasi dan Evaluasi Fast Disintegrating Tablet (FDT) Loratadin

Fast Disintegrating Tablet (FDT) adalah sediaan tablet yang hancur cepat di mulut yang membantu mempermudah penggunaannya khususnya saat tidak tersedia air. Permasalahan yang dihadapi pada formulasi FDT adalah waktu hancur yang sangat singkat dan masalah rasa untuk zat aktif yang berasa tidak enak. Tujuan dari penelitian ini adalah memformulasi sediaan FDT loratadin yang memiliki rasa pahit. FDT dibuat dengan metode kempa langsung menggunakan manitol yang digranulasi dengan PVP K-30 sebagai pengisi atau Parteck® M 200 dengan kombinasi Avicel PH-102. Formula tersebut selanjutnya dibuat tablet dengan cara menambahkan Ac-Di-Sol pada beberapa konsentrasi dan kekerasan yang berbeda. Evaluasi sediaan meliputi pengujian kekerasan, friabilitas, friksibilitas, waktu pembasahan, waktu hancur, penetapan kadar, kesukaan dan disolusi. Profil uji disolusi kemudian dibandingkan dengan tablet inovator konvensional, Claritin®. Hasil pengujian menunjukkan bahwa tablet yang dibuat dengan menggunakan granul manitol maupun Parteck® M 200 dengan Ac-Di-Sol sebagai bahan penghancur dengan konsentrasi 2,5% dan kekerasan tablet ±4 kg dapat menghasilkan FDT yang memenuhi syarat, termasuk dari segi rasa. Hasil uji disolusi dari FDT yang dihasilkan menunjukkan bahwa loratadin terdisolusi lebih cepat dibandingkan Claritin® dengan nilai f2 kurang dari 30.Kata Kunci: loratadin, fast disintegrating tablet, waktu hancur, disolusi, rasa.AbstractFast Disintegrating Tablet (FDT) is a tablet which rapidly disintegrate in the mouth that facilitate in their use, especially when water is not available. The problem in FDT formulation is a very short disintegration time and the bad taste of active substances. The aim of this study was to formulate FDT loratadine which has a bitter taste. FDT was made by direct compression using granulated mannitol with PVP K-30 or Parteck® M 200 combined with Avicel PH-102 as diluent. Tablet was then made by adding the various concentration of Ac-Di-Sol and at different of hardness. The tablet evaluation included hardness, friability, frictibility, wetting time, disintegration time, loratadine assay, panelists test and dissolution test. Dissolution profiles were then compared to innovator conventional tablet, Claritin®. The results showed that the tablets which made using granulated mannitol or Parteck® M 200 with 2,5% Ac-Di-Sol and at ± 4 kg of hardness could produce FDT that meet the requirements, included the taste. The dissolution test showed that loratadine from FDT formulation dissolved faster than Claritin® tablets with f2 values less than 30.Keywords: loratadine, fast disintegrating tablet, disintegration time, dissolution, tast

ROSELLA FLOWER (Hibiscus sabdariffa L.) EXTRACT DRYING THROUGH MICROENCAPSULATION OF SPRAY DRYING METHOD WITH MALTODEXTRIN

Roselle (Hibiscus sabdariffa L.) have a lot of pharmacological activities which have been widely reported both in vitro and in vivo and has been clinically tested. The usage of the extract in powder form would be more practical and scalable as a raw material and have advantages to facilitate its storage, distribution, standardization of active substances and can improve its stability. The objective of this research is to study the effect of maltodextrin addition for microcapsules formation related to roselle flower calyx extract powder characterized by using spray drying method. Research was carried out by made feed solution in ratio of 1: 1 (R1); 1: 2 (R2); and 1: 4 (R3) with a total solids content of 10%. Then, microencapsulated by spraydrying method with 110-115C inlet and 99-104C outlet temperature, and flow rate of 200 mL/hour. Microcapsules had characteristic morphological structures such as spheric form. The average particle size decreased with the addition of maltodextrin. The addition of maltodextrin can reduce the hygroscopicity of extracts and increase solubility in water and moisture content. Spray drying process in powder R2 give the encapsulation efficiency of 97.73% and product recovery of 74.05%. All powder microcapsules have residual solvent <1%

Preparasi dan Karakterisasi Polimorfisme Obat Anti Malaria Artesunate

PREPARASI DAN KARAKTERISASI POLIMORFISME OBAT ANTI MALARIA ARTESUNATE. Artesunate (AS) adalah derivat semisintetis dari Artemisinin, suatu obat anti malaria dari tumbuhan Artemisia annua yang terdiri atas struktur seskuiterpen endoperoksida. AS merupakan derivat artemisinin yang paling banyak digunakan sebagai obat antimalaria untuk menggantikan banyak obat malaria lain yang telah resisten terhadap malaria falsiparum. Khusus untuk AS, belum banyak studi yang dilakukan maupun literatur yang tersedia untuk mempelajari keadaan padatan (solid state) dan khususnya keberadaan polimorfisme dari AS. Polimorfisme dari suatu padatan memiliki fasa kristalin yang berbeda dalam susunan kisi kristal internalnya. Perbedaan kisi kristal (polimorfisme maupun pseudopolimorfisme) ini dalam bidang farmasi akan memberikan pengaruh terhadap ketersediaan hayati obat dan khasiat penggunaan obat secara klinis. Tujuan penelitian ini adalah untuk memperoleh dan mengamati perbedaan polimorfisme AS serta mengkarakterisasinya dengan analisis PXRD, IR dan DTA. Untuk lebih memperkuat hasil analisis, dilakukan juga cara mikroskopik baik dengan Hot Stage Microscopy (HSM) maupun dengan Scanning Electron Microscope (SEM). Hasil penelitian menunjukkan keberadaan dua bentuk polimorf yang berbeda dari obat antimalaria AS. Bentuk I merupakan bentuk komersial dari AS yang biasa digunakan sebagai bahan baku obat dan bentuk II diperoleh dari perlakuan bentuk I yang mengalami proses freeze drying