scholarly journals Alternative Methods for Dissolution Profile Comparison in the Dissolution Test

2021 ◽  
Vol 10 (4) ◽  
pp. 197-207
Author(s):  
D. P. Romodanovsky ◽  
D. V. Goryachev
Keyword(s):  
Active Substance ◽  
Dissolution Kinetics ◽  
Alternative Methods ◽  
Drug Dissolution ◽  
Dissolution Profile ◽  
Dissolution Test ◽  
Similarity Factor ◽  
Model Independent ◽  
Kinetics Of ◽  
Comparative Dissolution

Introduction. The article discusses the problem of assessing the similarity of the dissolution profiles of two batches of the nebivolol. The use of a generally accepted similarity factor for assessing equivalence is unacceptable in some cases, for example, for drugs with a high variability in the values of the release of the active substance from the formulation. At the same time, at present, there are no generally accepted approaches to comparing the profiles of the dissolution kinetics of drugs, with the exception of the method for assessing the comparability of profiles based on the mathematical calculation of the similarity factor f2, which has certain criteria that limit its application.Aim. To demonstrate alternative methods for assessing the similarity between the dissolution profiles of two drugs using a practical example.Materials and methods. The results of the comparative dissolution test of two series of nebivolol at a dosage of 5 mg. Five model-independent methods for assessing the equivalence of drug dissolution were used. Statistical data processing was performed using Microsoft Excel software.Results and discussion. The paper presents a practical example of using five alternative model-independent methods for assessing the equivalence of the dissolution profile. An example is used to illustrate the proposed equivalence limits and statistical methodology. Also, various approaches to determining the boundaries of equivalence have been proposed to assess the similarity of the dissolution profiles of an active substance.Conclusion. According to the results of the comparative dissolution test of two batches of nebivolol, it was shown that the use of the similarity factor as a criterion for assessing dissolution profiles led to a false positive result. In such cases, the possibility of using alternative methods for assessing the equivalence of dissolution profiles described in the article, or other methods presented in the scientific literature, should be considered, with a justification of their acceptability in each specific case.

scholarly journals Assessment of in Vitro Comparative Dissolution Kinetics of Moxonidine Products as a Factor Potentially Determining Effectiveness of Antihypertensive Treatment

2019 ◽  
Vol 14 (6) ◽  
pp. 951-957
Author(s):  
G. V. Ramenskaya ◽  
I. E. Shokhin ◽  
N. I. Gaponova ◽  
V. R. Abdrakhmanov
Keyword(s):  
Generic Drugs ◽  
Dissolution Kinetics ◽  
Acetate Buffer Solution ◽  
Medicinal Products ◽  
Buffer Solution ◽  
Reference Drug ◽  
Similarity Factor ◽  
Kinetics Of ◽  
Comparative Dissolution

Aim. Investigation of comparative dissolution kinetics of generic medicinal products containing moxonidine versus reference drug. Material and methods. Objects of the research were film-coated tablets containing moxonidine (INN) in a dose 0.4 mg: a reference drug Physiotens® and 4 generic drugs. In vitro dissolution test of moxonidine from the study drugs was performed using comparative dissolution kinetics test (CDKT). The CDKT was performed in the media with the following pH: 1.2 (1:9 mixture of 0.1 M hydrochloric acid and water), 4.5 (acetate buffer solution, prepared as per State Pharmacopoeia, XIII), and 6.8 (phosphate buffer solution, prepared as per State Pharmacopoeia, XIII). The sampling for dissolved moxonidine was performed 5, 10, 15, 20, and 30 min after the test was started. An high performance liquid chromatography method with ultraviolet detection at 220 nm was used to assay. Results. Within 15 min more that 85% of moxonidine dissolved from the reference drug and all study drugs at pH 1.2; dissolution profiles were similar without calculation of similarity factor f2. Similarly, at pH 4.5 dissolution profiles of study drugs #2 and #3 were similar to that of the reference drug, and the similarity factor f2 was not calculated. However, in case of study drugs #1 and #4 significant differences were observed at a single time point (15 min), which suggests that their dissolution profiles are non-similar to that of the reference drug. Similarity factors f2 were calculated 17.52 and 35.30, respectively (less than 50). At pH 6.8 similarity factors f2 for all study generic drugs were also less than 50 (23.8, 49.8, 38.6, and 35.9), so their dissolution curves were non-similar to that of reference drug. Conclusion. In our study we observed difference in release in vitro of medicinal products containing moxonidines: none of the study drugs was fully similar to the reference drug in all media. The differences observed at pH 6.8 were noteworthy, where the samples had or faster kinetics (study drugs #2 and #3), or slower dissolution kinetics (test drugs #1 and #4). Observed differences in moxonidine release rate may impact absorption of active pharmaceutical ingredient into the blood following drug administration.

scholarly journals Uji Disolusi Terbanding Tablet Ofloxacin Berlogo dan Generik Bermerek Terhadap Inovator Dalam Media Dapar HCl pH 4,5

2017 ◽  
Vol 4 (1) ◽  
Author(s):  
Winsa Wira Wijaya ◽  
Prima Happy Ratnapuri ◽  
Mia Fitriana
Keyword(s):  
Acetate Buffer ◽  
Dissolution Profile ◽  
Dissolution Test ◽  
Branded Drug ◽  
Similarity Factor ◽  
Difference Factor ◽  
Zwitter Ion ◽  
Dissolution Efficiency ◽  
Comparative Dissolution

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).

scholarly journals Effect of xanthan gum-based food thickeners on the dissolution profile of fluoroquinolones oral formulations

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Nobuyuki Takahashi ◽  
Yoshiaki Fujita ◽  
Nanako Takahashi ◽  
Akihiro Nakamura ◽  
Tsutomu Harada
Keyword(s):  
Aqueous Solution ◽  
Dissolution Rate ◽  
Xanthan Gum ◽  
Antimicrobial Agents ◽  
Guar Gum ◽  
Generic Drugs ◽  
Drug Dissolution ◽  
Dissolution Profile ◽  
Dissolution Test ◽  
The Impact

Abstract Background Xanthan gum-based food thickeners (XG-FTs) are often ingested by patients with dysphagia to prevent aspiration during drug treatment. Reportedly, XG-FTs affect tablet disintegration, drug dissolution rates, and reduce the efficacy of postprandial antihyperglycemic agents. The absorption rate and quantity of fluoroquinolone antimicrobial agents correlate with drug efficacy, raising concern about the impact of XG-FTs. Previously, we reported that film-coated tablets were less susceptible to the effects of XG-FT than conventional and orally disintegrating tablets. Here, we compare the effect of XG-FTs on dissolution profiles of three oral fluoroquinolone-based film-coated tablets by evaluating the dissolution of crushed products, fine granules, and film-coated fine granules. Methods We examined formulations of tosufloxacin tosylate monohydrate (TFLX), levofloxacin hemihydrate (LVFX), and ciprofloxacin hydrochloride hydrate (CPFX). The formulations were immersed in 20 mL of 1.5% (w/v) XG-FT aqueous solution for 2.5 min followed by a dissolution test using the paddle method according to the Japanese Pharmacopoeia (dissolution test solution pH 1.2; volume 900 mL; temperature 37 ± 0.5 °C). The dissolution profile was evaluated according to the dissolution quantity indicated in product specifications and guidelines for bioequivalence testing of generic drugs. The 15-min mean dissolution rate was determined for a formulation immersed in 1.5% (w/v) XG-FT aqueous solution and compared with that for a non-immersed formulation (control). Fluoroquinolone film-coated tablets were mixed with starch-based FTs, guar gum-based FTs, or XG-FTs to observe their appearances. Results The dissolution profile of LVFX film-coated tablets was not affected by XG-FTs, but the dissolution of TFLX and CPFX was delayed. For crushed film-coated tablets, the 15-min mean dissolution rate was significantly delayed for all three fluoroquinolones when compared with that of uncrushed products. The dissolution profile of TFLX film-coated fine granules was unchanged by XG-FTs. CPFX film-coated tablets and crushed products produced a gel-like precipitate when mixed with XG-FTs and failed to meet product-dissolution specifications. A gel-like precipitate was also observed with guar gum-based FTs. Conclusion The effect of XG-FTs on the dissolution profile of film-coated fluoroquinolone formulations varied depending on the formulation. The CPFX formulation formed a gel-like precipitate when immersed in XG-FTs resulting in a significantly delayed dissolution.

scholarly journals Evaluation of the Release Kinetics of a Pharmacologically Active Substance from Model Intra-Articular Implants Replacing the Cruciate Ligaments of the Knee

Materials ◽  
2019 ◽  
Vol 12 (8) ◽  
pp. 1202 ◽  
Author(s):  
Dorota Wojcik-Pastuszka ◽  
Justyna Krzak ◽  
Bartosz Macikowski ◽  
Ryszard Berkowski ◽  
Bogdan Osiński ◽  
...  
Keyword(s):  
Drug Release ◽  
Active Substance ◽  
Rate Constants ◽  
Incubation Temperature ◽  
Release Kinetics ◽  
Dissolution Kinetics ◽  
Second Order ◽  
Prolonged Release ◽  
Pharmacologically Active ◽  
Kinetics Of

Implants are readily applied as a convenient method of therapy. There is great interest in the prolonged release of active substances from implants. The objective of this work was to evaluate the dissolution kinetics of steroidal anti-inflammatory preparation (SAP) released from novel implants, and to test the influence of the technology on SAP release kinetics. The proposed long-acting preparations may overcome difficulties resulting from repeated injections and often visits to ambulatory clinic, as the stabilizing function of the artificial ligament would be enriched with pharmacological activity. The potential advantages provided by the new coatings of knee implants include the continuous, sustained, and prolonged release of an active substance. The study was carried out using a modified United States Pharmacopoeia (USP) apparatus 4. The amount of SAP was measured spectroscopically. It was revealed that the transport of the drug was mainly a diffusion process. The drug release kinetics was analyzed using zero-, first-, and second-order kinetics as well as Korsmeyer-Peppas, Higuchi, and Hixon-Crowell models. The highest values of the release rate constants were k0 = (7.49 ± 0.05) × 10−5 mg × min−1, k1 = (6.93 ± 0.05) × 10−6 min−1, and k2 = (7.70 ± 0.05) × 10−7 mg−1 × min−1 as calculated according to zero-, first-, and second-order kinetics equations, respectively. The values of the rate constants obtained for the slowest process were k0 = (3.63 ± 0.06) × 10−5 mg × min−1, k1 = (2.50 ± 0.03) × 10−6 min−1, and k2 = (2.80 ± 0.03) × 10−7 mg−1 × min−1. They may suggest the possibility of sustained release of betamethasone from the system. Due to the statistical analysis, differences were observed between most of the studied implants. Incubation, temperature, time of stabilization of layers, and the method of SAP deposition on the matrix affected the drug release.

scholarly journals Comparative studies of the kinetics of dissolution of medicines on the basis of clopidogrel

2021 ◽  
pp. 26-34
Author(s):  
O. P. Baula ◽  
O. O. Saliy ◽  
V. I. Bessаrabov ◽  
A. М. Gerasimchuk
Keyword(s):  
Comparative Studies ◽  
Generic Drugs ◽  
Dissolution Kinetics ◽  
Dissolution Test ◽  
Generic Medicines ◽  
Dissolution Medium ◽  
Clopidogrel Bisulfate ◽  
Kinetics Of Dissolution ◽  
Kinetics Of

Generic medicines occupy dominant positions both in the pharmaceutical market of Ukraine and in industrial production by domestic pharmaceutical enterprises. The use of generic drugs in medical practice is of significant medical and social importance for expanding the accessibility of the general population to essential drugs. In Ukraine, more than twenty generic medicines based on clopidogrel, both foreign and domestic, are registered. All generic drugs containing clopidogrel bisulfate must comply with pharmaceutical bisulfate must comply with pharmaceutical equivalence, the kinetics of release of the active pharmaceutical ingredient using the Dissolution test in vitro, and pharmacokinetic parameters in vivo. The aim of the work was to carry out comparative studies of the dissolution kinetics of four samples of generic drugs based on clopidogrel with the dissolution kinetics of the original drug Plavix®, to evaluate the similarity factor of dissolution profiles and to determine the effect of biopharmaceutical factors on the equivalence of generics. Comparative studies of the kinetics of dissolution were carried out by the in vitro method according to the «Dissolution» test using a device with a blade with a rotation speed of 50 rpm, a dissolution medium with a pH value of 2.0 in a volume of 900 ml at a temperature of 37 ± 1 °C. The determination of the quantitative content of clopidogrel, which passed into the dissolution medium, was carried out by the method of adsorption spectrophotometry in the ultraviolet region at a wavelength of about 240 ± 2 nm. Based on the data obtained, the dissolution profiles of the original drug Plavix® and the studied samples of generic drugs were constructed, the similarity of which was assessed by the value of the similarity factor. According to the research results, it was found that one sample of the generic drug proved its equivalence by the in vitro method to Plavix®, and three other samples of generics had differences in dissolution kinetics in comparison with the original drug. Biopharmaceutical factors were analyzed that could affect the dissolution kinetics of the studied generic drugs, from which the physicochemical characteristics of clopidogrel bisulfate, the qualitative and quantitative composition of excipients and the features of the technological process were determined. Thus, on the basis of the comparative studies of the dissolution kinetics of drugs based on clopidogrel, generics were found that did not correspond to the in vitro equivalence according to the Dissolution test to the original drug, which could be due to the influence of a combination of biopharmaceutical factors.

scholarly journals Comparative dissolution kinetics of biogenic and chemogenic uraninite under oxidizing conditions in the presence of carbonate

2009 ◽  
Vol 73 (20) ◽  
pp. 6065-6083 ◽  
Author(s):  
Kai-Uwe Ulrich ◽  
Eugene S. Ilton ◽  
Harish Veeramani ◽  
Jonathan O. Sharp ◽  
Rizlan Bernier-Latmani ◽  
...  
Keyword(s):  
Dissolution Kinetics ◽  
Kinetics Of ◽  
Comparative Dissolution

Study of Dissolution Kinetics of Mefenamic Acid Solid Dispersion with Polyvinylpyrrolidone

2021 ◽  
pp. 79-95
Author(s):  
R. Alrouhayya ◽  
T.F. Sheshko ◽  
E.B. Markova ◽  
V.S. Boldyrev ◽  
A.A. Razvodova ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Active Substance ◽  
Mefenamic Acid ◽  
Active Component ◽  
Solid Dispersions ◽  
Dissolution Kinetics ◽  
Biologically Active ◽  
Hydrophobic Nature ◽  
Kinetics Of ◽  
Low Solubility

The low solubility of a biologically active substance in an aqueous medium is often the main reason for the reduced therapeutic effect of drugs. The most common approach to solve this problem is to obtain a watersoluble salt of the active substance and an appropriate preparatory formulation based on it. In this case, the solubility of the obtained compound in hydrophobic systems decreases dramatically, which decreases the rate of transmembrane transport and changes the pharmacokinetic laws of the process. In practice, not only the dependence of the therapeutic effect on the salt compound properties, but also a complete loss of the drug active ingredient activity can be observed. The use of biologically active compound solid dispersions in watersoluble polymers is the most promising approach to increase the therapeutic effect of drugs while maintaining the hydrophobic nature of the active component, to reduce the dose load on the patient’s body and obtain prolonged action. In experiments we obtained solid dispersions of mefenamic acid in polyvinylpyrrolidone and studied kinetic regularities of solubility of this promising drug form in aqueous solution of phosphate buffer. By means of mathematical modelling it was found that the phenomenon under study is well described by Ritger --- Peppas model, which considers diffusion of biologically active component into solution according to Fick's law with possible influence on mass transfer at swelling and degradation of polymer matrix

scholarly journals Assessment of physicochemical properties and comparison of the dissolution profile of amoxicillin caplets

2020 ◽  
Vol 16 (2) ◽  
pp. 118-129
Author(s):  
Een Widiyasari ◽  
Teuku Nanda Saifullah Sulaiman
Keyword(s):  
Physicochemical Properties ◽  
Product Quality ◽  
Dosage Form ◽  
Reference Product ◽  
Immediate Release ◽  
Dissolution Profile ◽  
Type Ii ◽  
Dissolution Test ◽  
Disintegration Time ◽  
Similarity Factor

Background: Marketed drugs must meet the required standards to guarantee product quality. Amoxicillin is a generic compound marketed under various trademarks as copy drugs. Amoxicillin caplets are an immediate release dosage form of BCS class I. An essential aspect of evaluating copy drugs is to assess the equivalence for their treatment to the innovator drugs to ensure the safety and effectiveness of the circulating copy drugs. Objective: The study aims to evaluate the physicochemical properties and compare the dissolution profile of amoxicillin caplets available in the market. Methods: Five amoxicillin caplet products, four test products, and one reference product were tested for their physicochemical properties and dissolution. The dissolution test was carried out with a type II device at a speed of 75 rpm in 900 mL of media buffered at pH 1.2, 4.5, and 6.8 and at a temperature of 37 +/- 0.5degrees celcius. The dissolution profile was analyzed by comparing it with the similarity factor (f2) parameters. Results: Two of the four amoxicillin caplet products had a similar dissolution profile to the reference products, namely products A and B. Products C and D were dissimilar because f2 was lower than 50 at pH 4.5. The caplets tested had almost the same dimensions, and all caplets met the requirements for uniformity of content, hardness, disintegration time, and dissolution. Conclusion: Not all of the amoxicillin caplets in the market have a similar dissolution profile to the reference products. Keywords: caplets, amoxicillin, dissolution, similarity factor

Dissolution kinetics profile of the drug «Pimafucin®, vaginal suppositories 100 mg»

2021 ◽  
pp. 33-37
Author(s):  
Aleksandra Mikhailovna Volkova ◽  
Viktoriya Sergeevna Tyukova ◽  
Anastasiya Vladimirovna Meleshko ◽  
Stanislav Anatolievich Kedik ◽  
Aleksey Valerievich Panov
Keyword(s):  
Qualitative Analysis ◽  
Dissolution Kinetics ◽  
Uv Spectrophotometry ◽  
Dissolution Profile ◽  
Dissolution Test ◽  
Pharmaceutical Substances

The article presents the dissolution profile and the results of the dissolution test of the drug «Pimafucin®, vaginal suppositories 100 mg.» The samples were examined by UV-spectrophotometry. The relevance of the study is due to the prevalence and availability of this method for quantitative and qualitative analysis of pharmaceutical substances.

Sign in / Sign up

Export Citation Format

Share Document