Bioequivalence Evaluation of Two Brands of Lisinopril Tablets by in vitro Comparative Dissolution Test and in vivo Bioequivalence Test

ABSTRAK Uji disolusi terbanding merupakan pengujian yang dapat digunakan untuk memastikan ekivalensi dan sifat-sifat produk obat. Uji disolusi terbanding dilakukan dalam media disolusi dengan pH yang disesuaikan dengan kondisi in vivo yaitu pada pH 1,2; 4,5; dan 6,8. Obat generik dan generik bermerek yang wajib uji ekivalensi salah satunya yaitu ofloxacin. Ofloxacin merupakan suatu obat yang memiliki sifat kationik, anionik, dan zwitter ion. Penelitian ini bertujuan untuk menentukan ekivalensi profil disolusi terbanding yang dianalisis dengan parameter f1, f2, dan DE70 antara ofloxacin generik berlogo dan generik bermerek terhadap inovator dalam media dapar asetat pH 4,5. Uji disolusi dilakukan sesuai USP 32-NF 27 yaitu menggunakan alat uji tipe 2 pada suhu 37 ± 0,50C dengan kecepatan putar 50 rpm. Analisis hasil yang digunakan untuk menentukan ekivalensi profil disolusi yaitu difference factor (f1), similarity factor (f2), dan dissolution efficiency (DE70). Hasil penelitian ini memberikan kesimpulan bahwa sampel yang memiliki ekivalensi profil disolusi terbanding yang dianalisis dengan parameter f1, f2, dan DE70 terhadap produk inovator dalam media dapar asetat pH 4,5 yaitu sampel A (generik bermerek) dan sampel B (generik berlogo). Kata kunci : ofloxacin, disolusi terbanding, difference factor (f1), similarity factor (f2), dan dissolution efficiency (DE70). ABSTRACT Comparative dissolution is a test that can be used to ensure equivalence and properties of medicinal products. Comparative dissolution test has done in a dissolution medium with pH adjusted to in vivo conditions at pH 1,2; 4,5; and 6,8. One of generic and generic branded drug that need equivalence test is ofloxacin. Ofloxacin is a drug which are cationic, anionic, and zwitter ion. The aim of this study was to determine equivalence comporative of dissolution profiles, then analyzed with f1, f2, and DE70 parameters between generic and generic branded to innovators ofloxacin in media acetate buffer pH 4,5. Dissolution test was accordance to USP 32-NF 27 that used equipment test type 2 at temperature 37 ± 0,50 C with rotary speed 50 rpm. The analysis results were used to determine equivalence dissolution profile e.g. difference factor (f1), similarity factor (f2), and dissolution efficiency (DE70). The results this study showed that samples had equivalence comporative of dissolution profiles which were analyzed with f1, f2, and DE70 parameters to innovator product in media acetate buffer pH 4,5 was sample code A (generic branded) and sample code B (generic). Keywords: ofloxacin, comparative dissolution, difference factor (f1), similarity factor (f2), and dissolution efficiency (DE70).

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Combined Methodologies for Determining In Vitro Bioavailability of Drugs and Prediction of In Vivo Bioequivalence From Pharmaceutical Oral Formulations

Frontiers in Chemistry ◽

10.3389/fchem.2021.741876 ◽

2021 ◽

Vol 9 ◽

Author(s):

A. De Simone ◽

L. Davani ◽

S. Montanari ◽

V. Tumiatti ◽

S. Avanessian ◽

...

Keyword(s):

Drug Release ◽

Drug Concentration ◽

Dissolution Test ◽

Brand Name ◽

Artificial Membrane ◽

New Approach ◽

Oral Formulations ◽

Permeability Assay

With the aim of developing an in vitro model for the bioavailability (BA) prediction of drugs, we focused on the study of levonorgestrel (LVN) released by 1.5 mg generic and brand-name tablets. The developed method consisted in combining a standard dissolution test with an optimized parallel artificial membrane permeability assay (PAMPA) to gain insights into both drug release and gastrointestinal absorption. Interestingly, the obtained results revealed that the tablet standard dissolution test, combined with an optimized PAMPA, highlighted a significant decrease in the release (15 ± 0.01 μg min−1 vs 30 ± 0.01 μg min−1) and absorption (19 ± 7 × 10–6 ± 7 cm/s Pe vs 41 ± 15 × 10–6 cm/s Pe) profiles of a generic LVN tablet when compared to the brand-name formulation, explaining unbalanced in vivo bioequivalence (BE). By using this new approach, we could determine the actual LVN drug concentration dissolved in the medium, which theoretically can permeate the gastrointestinal (GI) barrier. In fact, insoluble LVN/excipient aggregates were found in the dissolution media giving rise to non-superimposable dissolution profiles between generic and brand-name LVN tablets. Hence, the results obtained by combining the dissolution test and PAMPA method provided important insights confirming that the combined methods can be useful in revealing crucial issues in the prediction of in vivo BE of drugs.

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REVITALISASI PENGGUNAAN OBAT GENERIK

Farmasains Jurnal Farmasi dan Ilmu Kesehatan ◽

10.22219/far.v1i2.1170 ◽

2012 ◽

Vol 1 (2) ◽

Author(s):

Nanang Yunarto

Keyword(s):

Generic Drugs ◽

Health Care Facilities ◽

Drug Dissolution ◽

Dissolution Test ◽

Test Results ◽

Drug Bioavailability ◽

Branded Drugs ◽

The Government

The government through the Ministry of Health is very serious about revitalizing the use of generic drugs by issuing a policy that stipulated in the Regulation of the Minister of Health No. HK. 02.02/Menkes/068/1/2010 about duty to use generic drugs in government health care facilities. To maximize the use of generic drugs, it is very important to improve understanding and trust of society that generic drugs have the quality, safety and effectiveness are similar to branded drugs. Besides that, there is a lot of research and the study of generic drugs will increase the knowledge, so that health professionals, especially doctors do not hesitate to prescribe generic drugs. Quality used as a basis of reference to establish the truth of the eficacy and safety. For availability of certain products can be demonstrated in vitro. Studies of drug dissolution gave the same indication with drug bioavailability. Ideally, in vitro drug dissolution correlates bioavailability in vivo. From the research results of dissolution test generic drugs Amoxiciline 500 mg tablets, Isosorbit Dinitrat 5 mg tablets and Omeprazole capsules compared to branded drugs show no less generic drugs than branded drugs, dissolution test results even better generic drugs

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The Development of Eudragit® NM-Based Controlled-Release Matrix Tablets

Medicina ◽

10.3390/medicina48040028 ◽

2012 ◽

Vol 48 (4) ◽

pp. 28 ◽

Cited By ~ 2

Author(s):

Kateřina Dvočková ◽

Rasa Kalėdaitė ◽

Jan Gajdziok ◽

Miloslava Rabišková ◽

Martina Bajerová ◽

...

Keyword(s):

Controlled Release ◽

Microcrystalline Cellulose ◽

Matrix Tablets ◽

Prolonged Release ◽

Dissolution Profile ◽

Dissolution Test ◽

Ph Level ◽

Controlled Release Tablets

Eudragit® NM was investigated as a matrix former in combination with microcrystalline cellulose as an insoluble filler for preparing controlled-release tablets containing model drugs with different solubility. Material and Methods. Three sets of matrix tablets differing in the drug-to-filler ratio (1:1, 2:1, and 4:1) and polymer amount with diltiazem hydrochloride (freely soluble) or caffeine (sparingly soluble) were prepared. Samples were evaluated by the dissolution test at pH 6.8 corresponding to the upper part of the small intestine; the selected samples were tested at a changing pH level to better simulate in vivo conditions. Results. The prepared matrix tablets fulfilled all the requirements of the European Pharmacopoeia. Tablets with Eudragit® NM showed excellent mechanical characteristics. In vitro studies showed that the set 1:1 was the most suitable for the sustained release of a freely soluble drug concerning the burst effect and the total drug amount released within 12 hours. The significant effect of the drug-to-filler ratio and polymer amount on the dissolution profile was confirmed by similarity factor analysis. A faster drug release was observed during the dissolution test within changing pH levels because of the pH-dependent solubility of diltiazem. A prolonged release of the sparingly soluble drug was not achieved, and a trend for fast disintegration was observed. Conclusions. The combination of Eudragit®NM with microcrystalline cellulose as an insoluble filler seems to be suitable only for freely soluble drugs, when the amount of the drug and the filler is similar.

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