Optimasi Hidroksipropil Metilselulosa K-4M dan Carbopol® 940  pada Sediaan Patch Dispersi Padat Piroksikam

Abstrak Piroksikam merupakan anti inflamasi non steroid (AINS) turunan oksikam yang berkhasiat sebagai analgesik dan antiinflamasi digunakan untuk pengobatan rheumatoid arthritis dan osteoarthritis. Piroksikam menyebabkan masalah pada saluran cerna dan first pass metabolism yang dapat dihindari dengan cara pemberian transdermal patch. Salah satu komponen patch yaitu polimer yang berfungsi untuk mengontrol kecepatan pelepasan obat dari sediaan. Penelitian ini dilakukan untuk menentukan komposisi terbaik dari kombinasi polimer hidroksipropil metilselulosa (HPMC) dan Carbopol terhadap % moisture content (MC) dan flux pelepasan sediaan transdermal patch dispersi padat piroksikam dengan rancangan formula Simplex Lattice Design. Piroksikam dibuat dalam bentuk dispersi padat dengan pembawa PEG 4000 untuk meningkatkan kelarutannya. Rancangan formula patch dispersi padat piroksikam dibuat dengan menggunakan tiga polimer Etil selulosa:HPMC:carbopol dimana yang divariasikan adalah perbandingan HPMC : Carbopol yaitu 1 : 0 ; 0,5 : 0,5 ; 0 : 1. Hasil uji menunjukkan ketiga formula memenuhi persyaratan keseragaman kadar dengan rentang keseragaman 3,735 – 97,349 %. Hasil juga menunjukkan formula 3 menghasilkan patch yang lebih tebal, pH permukaan patch lebih rendah, nilai % moisture content lebih besar dan nilai flux lebih tinggi dibandingkan formula 2 dan formula 3, Formula 3 mempunyai nilai % moisture content yang memenuhi persyaratan sebesar 6,613% dan nilai flux pelepasa yang paling bagus sebesar 32,562 µg/cm2.menit1/2. Hasil penelitian juga menunjukkan formula 1 memiliki keseragaman bobot lebih baik dibandingkan formula 2 dan formula 3. Dapat disimpulkan bahwa komposisi optimum dari kombinasi polimer HPMC dan Carbopol pada sediaan patch dispersi padat piroksikam yaitu formula dengan komposisi polimer HPMC sebanyak 0 mg dan Carbopol sebanyak 75 mg. Kata kunci: Dispersi padat, patch piroksikam, HPMC, Carbopol Optimization of Hydroxypropyl Methylcellulose K-4M and Carbopol® 940 in Solid Dispersion Piroxicam Patch Abstract Piroxicam is a non-steroidal anti-inflammatory (NSA) oxysmic derivative as an analgesic and anti-inflammatory agent used for the treatment of rheumatoid arthritis and osteoarthritis. Piroxicam causes problems in the gastrointestinal tract and first pass metabolism that can be avoided by giving transdermal patches. One of the patch components is a polymer that serves to control the speed of drug release from the preparation. The present study was conducted to determine the best composition of the combination of hydroxypropyl methylcellulose (HPMC) and Carbopol polymers against% moisture content (MC) and fluxes release of the pyroxicam dispersion transdermal patch dispersion with the design of the Simplex Lattice Design formula. Piroxicam is prepared in the form of a solid dispersion with a PEG 4000 carrier to increase its solubility. The design of a pyroxicam solid dispersion patch formulation was prepared using three ethyl cellulose polymers: HPMC: carbopol wherein the HPMC ratio is computed: Carbopol is 1: 0; 0.5: 0.5; 0: 1. The test results show the three formulas meet the requirements of uniformity of the content with a uniformity range of 3.735 - 97.349%. the results also show formula 3 resulting in thicker patches, lower patch pH surfaces, greater moisture content values and higher flux values than formula 2 and formula 3, Formula 3 has a moisture content value of 6.613% the finest fl ux flux of 32,562 μg / cm2.menit1 / 2. The results also show that formula 1 has better weight uniformity than formula 2 and formula 3. It can be concluded that the optimum composition of HPMC and Carbopol polymer combinations in the preparation of piroxicam solid dispersion patch is a formula with HPMC polymer composition as 0 mg and Carbopol as much as 75 mg.. Key words: solid dispersion, piroxicam patch, HPMC, Carbopol

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Optimasi Hidroksipropil Metilselulosa K-4M dan Carbopol® 940 pada Sediaan Patch Dispersi Padat Piroksikam

Kartika Jurnal Ilmiah Farmasi ◽

10.26874/kjif.v5i2.133 ◽

2018 ◽

Vol 5 (2) ◽

pp. 80

Author(s):

Dwi Nurahmanto ◽

Nurul Shalikha ◽

Lidya Ameliana

Keyword(s):

Moisture Content ◽

Solid Dispersion ◽

Hydroxypropyl Methylcellulose ◽

Lattice Design ◽

Simplex Lattice Design ◽

Peg 4000 ◽

First Pass Metabolism ◽

First Pass ◽

Simplex Lattice ◽

Pass Metabolism

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OPTIMASI POLIVINILPIROLIDON DAN CARBOPOL PADA SEDIAAN PATCH DISPERSI PADAT PIROKSIKAM

Jurnal Ilmiah Manuntung ◽

10.51352/jim.v3i2.129 ◽

2018 ◽

Vol 3 (2) ◽

pp. 197

Author(s):

Dwi Nurahmanto ◽

Friska Wira Sabrina ◽

Lidya Ameliana

Keyword(s):

Solid Dispersion ◽

Lattice Design ◽

Simplex Lattice Design ◽

Peg 4000 ◽

First Pass Metabolism ◽

First Pass ◽

Inflammatory Drugs ◽

Simplex Lattice ◽

Optimum Formula ◽

Pass Metabolism

Piroxicam, a non steroidal anti inflammatory drugs (NSAID), is an oxicam derivative which can be used for treatment of various rheumatic diseases, such as rheumatoid arthritis and osteoarthritis. Piroxicam patch is an affective approach evading piroxicam’s side effect such as peptic ulcer and first pass metabolism. One of the patch components is polymer that the function is to control the speed of drug release from the patch. The aims of this study were to determine the optimum formula of a combination of polyvinylpyrolidone (PVP) and Carbopol to % moisture content (MC) and the flux release in solid dispersion piroxicam patch using Simplex Lattice Design. Piroxicam was prepared in the form of a solid dispersion in PEG 4000 to increase its solubility. The design formula of solid dispersion piroxicam patch made with the ratio PVP : Carbopol, that were 1 : 0; 0.5 : 0.5; 0 : 1. The optimum formula was chosen with the ratio PVP : Carbopol, 1: 0, which gave the best result of % MC and flux release. The result of % MC was 6.91% and the result of flux release was 35.543 µg/cm2.menit1/2.

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Preparation and evaluation of an ispaghula based directly compressible matrixing agent for controlled release

Acta Pharmaceutica ◽

10.2478/v10007-008-0015-2 ◽

2008 ◽

Vol 58 (3) ◽

pp. 309-316 ◽

Cited By ~ 1

Author(s):

Anita Lalwani ◽

Jolly Parikh

Keyword(s):

Controlled Release ◽

Hydroxypropyl Methylcellulose ◽

Hydrogen Phosphate ◽

Lattice Design ◽

Phosphate Dihydrate ◽

Simplex Lattice Design ◽

Dependent Variables ◽

Simplex Lattice ◽

Preparation And Evaluation

Preparation and evaluation of an ispaghula based directly compressible matrixing agent for controlled releaseThe objective of the present investigation was to prepare and evaluate an ispaghula husk based directly compressible (DC) adjuvant that can be used as matrixing agent using an agglomeration technique. Addition of hydroxypropyl methylcellulose was found necessary to improve cohesion. Lactose (X1), calcium hydrogen phosphate dihydrate (X2) and Avicel PH101 (X3), used along with ispaghula in preparation of agglomerates, were selected as three independent variables in a simplex lattice design affecting compressional and dissolution characteristics of the drug from the DC adjuvant. The agglomerates were evaluated for their flow properties. Tablets were prepared using 70% agglomerates and 30% acetaminophen, a poorly compressible drug, and were subjected toin vitrodrug release study. Amounts of the drug released at the end of 60 min (Y60), 300 min (Y300) and 480 min (Y480) were selected as dependent variables in a simplex lattice design. Batch IH05 that contained lactose and calcium hydrogen phosphate dihydrate in a 1:2 ratio could control the release for 12 hours and thus form the basis for twice a-day-dosing.

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The Optimization of Maltodextrin and Arabic Gum in the Microencapsulation of Aqueous Fraction of Clinacanthus nutans Using Simplex Lattice Design

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v8i2.13877 ◽

2018 ◽

Vol 8 (2) ◽

Author(s):

Intan Martha Cahyani ◽

Ebta Narasukma Anggraeny ◽

Bekti Nugraheni ◽

Christiana Retnaningsih ◽

V Kristina Ananingsih

Keyword(s):

Antioxidant Activity ◽

Moisture Content ◽

Flow Rate ◽

Aqueous Fraction ◽

Arabic Gum ◽

Design Expert ◽

Lattice Design ◽

Simplex Lattice Design ◽

Clinacanthus Nutans ◽

Simplex Lattice

The aqueous fraction of Clinacanthus nutans leaf extracts contains flavonoids which known had antioxidative properties. To improve acceptability, this viscous and bitter aqueous fraction was microencapsulated using maltodextrin and Arabic gum. This research aims to discover the effectivity of maltodextrin and Arabic gum and the concentrations for optimum microencapsulation. Optimization design was done using Design Expert with simplex lattice design with ratios of 1:0; 0.75:0.25; 0.5:0.5; 0.25:0.75 and 0:1. The evaluations done to the results were microcapsule yield, moisture content, flow rate, and antioxidant activity. The optimum ratio of maltodextrin and Arabic gum was obtained at 0.806:0.194 with 1.49% moisture content, flow rate 4.375 g/s and antioxidant activity at the value of 842,499 ppm. The result of one-sample T-test showed that the prediction result of Design Expert did not differ significantly from the experiment result. From the data, it was concluded that the resulting equation was valid

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Application of simplex lattice design for the development of extended release tablets of model drug diclofenac sodium

Therapeutic Delivery ◽

10.4155/tde-2019-0034 ◽

2019 ◽

Vol 10 (8) ◽

pp. 515-525

Author(s):

Shivaji Phadke ◽

Tanvi Kanekar ◽

Suhas Gumaste ◽

Vaishnavi Parikh

Keyword(s):

Drug Release ◽

Extended Release ◽

Diclofenac Sodium ◽

Hydroxypropyl Methylcellulose ◽

Dicalcium Phosphate ◽

Wet Granulation ◽

Lattice Design ◽

Simplex Lattice Design ◽

Component Design ◽

Simplex Lattice

Aim: Simplex lattice design was applied to predict extent of drug release from extended release diclofenac sodium tablets. Methods: The effects of composition on dissolution rate were evaluated by varying the levels of hydroxypropyl methylcellulose, dicalcium phosphate and cornstarch via three component design. Results: The rate of drug release was primarily dictated by the proportion of hydroxypropyl methylcellulose and was also affected by the proportion of dicalcium phosphate and the method of processing (direct compression/wet granulation). Polynomial equations constructed for directly compressed and wet-granulated formulations could successfully predict the extent of drug release at an arbitrary time point of 3 h. Conclusion: Simplex lattice design is a viable tool to predict the drug release patterns of extended release formulations.

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High-Payload Buccal Delivery System of Amorphous Curcumin–Chitosan Nanoparticle Complex in Hydroxypropyl Methylcellulose and Starch Films

International Journal of Molecular Sciences ◽

10.3390/ijms22179399 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9399

Author(s):

Li Ming Lim ◽

Kunn Hadinoto

Keyword(s):

Oral Delivery ◽

Hydroxypropyl Methylcellulose ◽

Buccal Delivery ◽

Limited Effectiveness ◽

First Pass Metabolism ◽

First Pass ◽

Starch Films ◽

Hydroxypropyl Starch ◽

High Payload ◽

Pass Metabolism

Oral delivery of curcumin (CUR) has limited effectiveness due to CUR’s poor systemic bioavailability caused by its first-pass metabolism and low solubility. Buccal delivery of CUR nanoparticles can address the poor bioavailability issue by virtue of avoidance of first-pass metabolism and solubility enhancement afforded by CUR nanoparticles. Buccal film delivery of drug nanoparticles, nevertheless, has been limited to low drug payload. Herein, we evaluated the feasibilities of three mucoadhesive polysaccharides, i.e., hydroxypropyl methylcellulose (HPMC), starch, and hydroxypropyl starch as buccal films of amorphous CUR–chitosan nanoplex at high CUR payload. Both HPMC and starch films could accommodate high CUR payload without adverse effects on the films’ characteristics. Starch films exhibited far superior CUR release profiles at high CUR payload as the faster disintegration time of starch films lowered the precipitation propensity of the highly supersaturated CUR concentration generated by the nanoplex. Compared to unmodified starch, hydroxypropyl starch films exhibited superior CUR release, with sustained release of nearly 100% of the CUR payload in 4 h. Hydroxypropyl starch films also exhibited good payload uniformity, minimal weight/thickness variations, high folding endurance, and good long-term storage stability. The present results established hydroxypropyl starch as the suitable mucoadhesive polysaccharide for high-payload buccal film applications.

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Design, Development and Characterization of Nifedipine Microspheres

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v9i3.2627 ◽

2019 ◽

Vol 9 (3) ◽

pp. 138-146

Author(s):

Arun Kumar Chalamalasetty ◽

Boggula Narender ◽

Bolledla Nirosha ◽

Bakshi Vasudha ◽

Peddapalli Himabindu

Keyword(s):

Particle Size ◽

Drug Release ◽

Oral Bioavailability ◽

Ethyl Cellulose ◽

Hydroxypropyl Methylcellulose ◽

Prolonged Release ◽

Design Development ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism

Back ground: Nifedipine is a calcium channel blocker and is used in treatment of angina of angina pectoris and hypertension. Nifedipine readily and almost completely absorbed from GIT, but undergoes first pass metabolism, resulting in low oral bioavailability is about 50%. Aim: The aim of the present study was to prepare and evaluate the microspheres of nifedipine with a goal of improving the bioavailability and giving a prolonged release of drug. Method: Emulsification (o/w) solvent evaporation method was employed in the preparation of nifedipine microparticles using ethyl cellulose and combination of ethyl cellulose and hydroxypropyl methylcellulose as the polymers. Results: FT-IR spectra of physical mixture showed no significant shifting of the peaks therefore it reveals that the drug is compatible with the polymer used. The percentage yield obtained in all the formulations was good and in the range of 59.25-94.44%. Among all the formulations, formulation with combination of ethyl cellulose and hydroxypropyl methylcellulose polymers M9 showed high amount of drug release i.e. (91.23%) in 12hrs. Drug release from microspheres with small mean particle size was faster than those with large mesh particle size and followed Higuchi model of kinetics. Conclusion: The obtained results could be used as essence to develop microspheres, which bypasses first-pass metabolism and results in the improvement of bioavailability. Hence, the present study has been a satisfactory attempt to formulate microspheres of nifedipine, with a view of improving its oral bioavailability and giving a prolonged release of drug. Keywords: Microspheres, nifedipine, hydroxypropyl methylcellulose E5, ethyl cellulose.

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Identification of a Cranberry Juice Product Capable of Inhibiting Enteric CYP3A-Mediated First-Pass Metabolism in Humans

Planta Medica ◽

10.1055/s-2008-1075176 ◽

2008 ◽

Vol 74 (03) ◽

Author(s):

N Ngo ◽

Z Yan ◽

TN Graf ◽

DR Carrizosa ◽

EC Dees ◽

...

Keyword(s):

Cranberry Juice ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism

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Development, Characterization and Optimization of Mucoadhesive Tablet for Buccal Delivery of Domperidone

Drug Delivery Letters ◽

10.2174/2210303108666181108120840 ◽

2019 ◽

Vol 9 (1) ◽

pp. 37-49

Author(s):

Jagdale Sachin ◽

Panbude Aishwarya ◽

Navasare Priya

Keyword(s):

Drug Release ◽

Factorial Design ◽

Research Work ◽

Wet Granulation ◽

Buccal Delivery ◽

Scanning Calorimetry ◽

Mucoadhesive Polymers ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism

Background and Objective: Upon oral administration domeperidone is rapidly absorbed, but subjected to the first pass effect which lowers systemic bioavailability to 15%. Mucoadhesive tablet can remain attached to buccal mucosa and becomes capable of bypassing hepatic first-pass metabolism to improve absorption directly into systemic circulation. The present research work was carried with an aim to develop, evaluate and optimize mucoadhesive tablet containing domperidone (DOME) for buccal delivery using different bio-adhesive polymeric combinations. Methods: The buccal tablets were formulated by wet granulation method using isopropyl alcohol. The preliminary formulations were prepared using combinations of HPMC K4, HPMC K15, HPMC K100, HPMC E5 as mucoadhesive polymers. 32 full factorial design was applied to determine the effect of independent variables like concentration of mucoadhesive polymers (HPMC K15 and HPMC K100) over dependent variables like mucoadhesive properties (swelling index, bioadhesive strength and in vitro drug release). The prepared mucoadhesive tablets were evaluated for their tablet properties and mucoadhesive properties. The interactions between drug and polymers were studied by Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). Results: All formulations of factorial design showed satisfactory physicochemical, mechanical and bioadhesive characteristics. The formulation F9 exhibited maximum cumulative drug release, mucoadhesive strength and swelling index. Conclusion: The developed buccal tablet of domperidone might prove alternative to bypass the hepatic first pass metabolism and to avoid degradation which in turn may result in reducing the frequency of administration. Thus, mucoadhesive tablet of domeperidone may become viable alternative overcoming the side effects; achieving greater therapeutic effectiveness and improving the patient compliance.

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