Drug Dissolution Testing Research Articles

QUALITY ASSESSMENT OF VARIOUS BRANDS OF CEFIXIME 400 MG CAPSULES AVAILABLE IN YEMENI MARKET

Objective: The study aimed to assess the quality control of different brands of cefixime 400 mg capsule brands available in Yemeni drug market. Methods: The pharmacopeial specifications of five cefixime 400 mg capsule brands available in Yemeni drug market, including two domestic brands, were assessed in this study. Assessment included assay content, capsule weight variation and disintegration. In addition, drug dissolution and antimicrobial activity test were assessed. Results: Out of five brands, three brands of cefixime 400 mg capsules passed official specified assay tests according to United States Pharmacopeia (USP) specifications. The five brands showed a similar profile of weight variation and drug disintegration that were within the limits. However, the results of drug content for five brands showed in range 78.78-104.46 % in which three brands (B, D and E) in compliance to USP specifications (90-110%) and two brands (A and C) not compliance to USP specification. Also, the results of dissolution profile were in range 86.2-109.8% for four brands (A, B, D and E) that compliance to USP specifications, and 73.56% for brand C that was not compliance to USP specifications. Conclusion: Based on the results obtained in this study, the drug content for three brands (B, D, E) is within the pharmacopeial limit, but the drug content of (A, C) is out of the limit. while the capsule disintegration, weight variations, and antibacterial activity in all tested brands are within the pharmacopeial limit. The dissolution profile for four brands (A, B, D, E) is within the pharmacopeial limit, but the dissolution profile for (C) is less than the allowed limit.

Formulation and Physical Evaluation of CTM Tablets by Direct Compression Method: A Systematic Literature Review

The direct compression method is one of the well-known formulation approaches in tablet manufacture. In this method, the active ingredients and additives of the formulation are mixed together and then compressed into tablets using a special device such as a compression machine. This study is a systematic review that aims to explore the formulation and physical evaluation of CTM tablets by direct compression method. The literature search process was carried out on various databases (PubMed, Web of Sciences, EMBASE, Cochrane Libraries, and Google Scholar) regarding the formulation and physical evaluation of CTM tablets by direct compression method. This study follows the preferred reporting items for systematic reviews and meta-analysis (PRISMA) recommendations. The direct compression method enables the manufacture of CTM tablets in a single production step, reducing the complexity and time required. The CTM tablet formulation process using the direct compression method involves homogeneous mixing of the raw materials and direct compression of the mixture into tablets using a compression machine. The direct compression method has advantages in production efficiency, simplicity, and cost-effectiveness, controlling the dosage of the drug contained in the tablet, and physical uniformity of the tablet. However, the direct compression method also has drawbacks, such as the risk of material segregation, difficulty in achieving controlled drug release, and the potential for direct effects on the active ingredients. Physical evaluation of tablets involves measuring the weight, thickness, and diameter of the tablets, as well as hardness or compressive strength tests to ensure the physical quality of the tablets produced. Drug release tests and dissolution tests were carried out to ensure that the CTM tablets released the drug consistently and under control according to regulatory requirements. Stability tests and chemical tests were carried out to check the physical and chemical changes of the tablets during storage and to ensure the integrity and purity of chlorpheniramine.

Development of Biopredictive Dissolution Method for Extended-Release Desvenlafaxine Tablets.

This study aimed to develop a biopredictive dissolution method for desvenlafaxine ER tablets using design of experiments (DoE) and physiologically based biopharmaceutics modeling (PBBM) to address the challenge of developing generic drug products by reducing the risk of product failure in pivotal bioequivalence studies. For this purpose, a PBBM was developed in GastroPlus® and combined with a Taguchi L9 design, to evaluate the impact of different drug products (Reference, Generic #1 and Generic #2) and dissolution test conditions on desvenlafaxine release. The influence of the superficial area/volume ratio (SA/V) of the tablets was observed, mainly for Generic #1, which presented higher SA/V than the others, and a high amount of drug dissolved under similar test conditions. The dissolution test conditions of 900 mL of 0.9% NaCl and paddle at 50 rpm with sinker showed to be biopredictive, as it was possible to demonstrate virtual bioequivalence for all products, despite their release-pattern differences, including Generic #3 as an external validation. This approach led to a rational development of a biopredictive dissolution method for desvenlafaxine ER tablets, providing knowledge that may help the process of drug product and dissolution method development.

Preparation and characterization of naproxen solid dispersion using different hydrophilic carriers and in-vivo evaluation of its analgesic activity in mice

BackgroundSolid dispersion (SD) has been used conventionally as a successful technique for improving the dissolution profile and bioavailability of poorly water-soluble drugs. The aim of this study was to progress the dissolution rate and bioavailability of naproxen (BCS class II) by SD technique. Materials & methodsIn this study, hydrophilic carriers are used for preparing solid dispersion of naproxen by evaporation method. The prepared optimized SDNs were evaluated by in-vitro drug dissolution test, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The in-vivo analgesic effects tests of the optimized SDNs (SDN-2 and SDN-5) were performed by tail immersion method and writhing method. ResultsAll the prepared SDNs exhibited a significant increase in the dissolution of naproxen compared to that of the pure drug. Among them, SDN-2 (the dispersion with sodium starch glycolate at 1:2 ratio of naproxen and sodium starch glycolate) and SDN-5 (using the combination of PEG-8000 and sodium starch glycolate with naproxen at 1:1:1 ratio) showed faster dissolution rate as compared to other solid dispersions (SDNs) and pure naproxen. SDN-2 showed 5.4 times better dissolution rate and SDN-5 depicted 6.5-fold increment of dissolution rate compared to pure naproxen drug. DSC, PXRD and SEM microscopy showed that the drugs crystallinity was decreased during the preparation process. FTIR study revealed that naproxen was stable in polymeric dispersions and there was no interaction among the drug and polymers. In writhing method, the percentage inhibition of the number of writhes showed significantly greater (p < 0.01), (p < 0.0001) analgesic activity for the higher dose treatment groups SDN-2(H), and SDN-5(H), respectively, when contrasted to the pure drug naproxen. For tail immersion test, there is increase in latency time at 90 min which is significantly greater (P < 0.01), (P < 0.05), (P < 0.01) for treatment groups SDN-2(H), SDN-5(L), and SDN-5(H), respectively that ultimately authenticates that the optimized SDNs (SDN-2, SDN-5) showed better analgesic activity in mice in comparison with the pure drug. ConclusionIt can be concluded that dissolution of the naproxen could be improved by the making solid dispersion using sodium starch glycolate and/or combination of sodium starch glycolate and PEG 8000 due to the complete transformation of drug into amorphous form with the entire loss of crystallinity, as evidenced by DSC, PXRD, and SEM and also consequences the enhanced analgesic activity in mice.

Computational prediction of pharmacokinetic parameters as an in vitro approach for assessing paracetamol tablets for IVIVC; a strategy in COVID-19 disruptive times.

In vitro-in vivo correlation (IVIVC) is a desirable attribute for any drug dissolution test to establish relevance and confidence in evaluating the quality and safety of products. The pharmacokinetic parameters of paracetamol have been studied extensively but information about the IVIVC is scanty and mostly controversial; this justifies its choice as a model drug for this study. This work is aimed to evaluate and compare the IVIVC dissolution profile of different brands of paracetamol tablets using authentic pharmacokinetic parameters such as; maximum observed dug concentration (Cmax), time to reach Cmax (Tmax) and Area under Curve concentration-time curve (AUC) obtained from literature. In vitro release data were obtained for each brand (n=12) using the USP II apparatus at 50 rpm in 900 ml phosphate buffer of pH 5.8, maintained at 37±0.5 °C and the results were mathematically extrapolated to predict in vivo data. The percent predicted error (% PE) for Cmax ranges from 1.70 to 6.52 % across the brands, while those for Tmax and AUC were &lt; 0 % and &gt; 20 % respectively. The observed low prediction error for Cmax and Tmax (&lt;10 %) demonstrated that the paracetamol IVIVC model was valid based on FDA guidelines. While a satisfactory result could not be achieved for AUC, promising results were obtained exploiting the convolution based IVIVC model.

Solubility Enhancement of a Poorly Water-Soluble Drug Using Hydrotropy and Mixed Hydrotropy-Based Solid Dispersion Techniques.

The biopharmaceutics classification system places rosuvastatin calcium in class II has a low and fluctuating oral bioavailability. The research focus is to maximize rosuvastatin calcium solubility in water and dissolution rate by employing and combining various hydrotropic agents to make a solid dispersion using solvent evaporation techniques. Methodology. The experimental study was conducted at Duhok University, College of Pharmacy. Initially, assess rosuvastatin's solubility in hydrotropic agents including urea, mannitol, citric acid, sodium benzoate, and sodium salicylate at concentrations of 10, 20, 30, and 40% w/v. Then, various ratios of 2 and 3 hydrotropic agents were employed to reduce the concentration of each hydrotropic agent. By using a solvent evaporation procedure, solid dispersions were made. The solid dispersion powders underwent evaluation for their percentage drug content, percentage yield, solubility, dissolution test, XRD, DSC, SEM, and FTIR. For statistical analysis, GraphPad InStat Demo software was used to conduct a two-way analysis of variance (ANOVA). In comparison to the pure drug, the solubility of hydrotropic solid dispersions and physical mixtures of rosuvastatin with a combination of hydrotropic agents (sodium salicylate, sodium benzoate, and urea) in the ratio of 13.33 for each increased in all formulations significantly, and all manufactured formulations' drug release ranged from 98.83 to 104.78%, indicating a noticeably higher dissolution rate. The concept of mixed hydrotropic solid dispersion was shown to be an original, risk-free, and cost-effective method for enhancing the bioavailability of drugs that have a low degree of solubility in water.

Detecting Crystallinity in Amorphous Solid Dispersions Using Dissolution Testing: Considerations on Properties of Drug Substance, Drug Product, and Selection of Dissolution Media

Dissolution testing has long been used to monitor product quality. Its role in quality control of amorphous solid dispersion (ASD) formulations is relatively new. In the presence of the crystalline phase, the dissolution of ASDs is determined by the dynamics between the dissolution rate of the amorphous solids and the rate of crystal growth. The detection of crystalline phase by dissolution test has not been well understood in the context of drug properties, formulation characteristics and dissolution test variables. This study systematically evaluated the impact of key parameters such as intrinsic crystallization tendency of the API, drug loading, extent of dissolution sink conditions and level of crystallinity on the ASD dissolution behavior. The results indicated diverse dissolution behaviors due to the differences in the intrinsic crystallization propensity of the drug, the drug loading, the ASD polymers and the dissolution sink index. Each of the complex dissolution profiles were interpreted based on visual observations during dissolution, the appropriate sink index based on the amorphous solubility, and the competition between drug dissolution versus crystallization. The findings of this study provide insights towards the various considerations that should be taken into account towards rationally developing a discriminatory dissolution method.

A Brief Review on Dissolution Method Development

Dissolution testing is a critical methodology; widely utilized in the development of a new pharmaceutical product. The test, in its simplest form, consists of placing the formulation in a dissolution apparatus containing suitable dissolution medium. The BCS has been a predictive tool for assess the prospective effects of formulation on the human, drug oral bioavailability. When used in combination with in vitro dissolution tests, the BCS can maintain the prediction of in vivo product performance and the development. Filtration is critical in drug dissolution testing as filtration stops the dissolution process and allows for accurate quantitation through separation of dissolved and un-dissolved components. The objective of this investigation was to determine if other sinker shapes will influence the rate, extent, or variability of dissolution. Dissolution test is required to study the drug release from the dosage form and its in vivo performance. Dissolution test is used to asses the lot-to-lot quality of drug product. development and validation of dissolution procedure(s) and to provide practical approaches for determining specificity, linearity, range, accuracy, precision, LOD, LOQ and robustness of methods.

The Molded Tablet, a disintegrant-free orally disintegrating tablet, resists thickening solution-reduced drug dissolution

In clinical practice, a thickening solution is frequently coadministered with medicinal tablets to facilitate swallowing by older patients. This study investigated the effect of thickening solutions on the reduction in drug dissolution from orally disintegrating tablets (ODTs) by testing a disintegrant-free ODT, the Molded Tablet (MT), and various disintegrant-containing ODTs. After measurement of the tensile strength of the test ODTs, a drug dissolution test was performed on ODTs treated with or without thickening solutions. Drug dissolution from the common disintegrant-containing ODTs was reduced significantly by treatment with thickening solutions, but the reduction was more moderate for the test MT. The present study also measured the swelling behavior and mechanical strength of the test ODTs after treatment with thickening solution. We observed that the MTs displayed less swelling in the thickening solution and that the swollen tablets had lower mechanical strength than the disintegrant-containing ODTs. This study suggests that the disintegrants contained in ODTs play a key role in reducing drug dissolution accompanied by treatment with a thickening solution, i.e., the disintegrants allow the ODT to interact closely with the thickening solution and this interaction has a substantial impact on the drug dissolution from ODTs.

Development of novel univariate and multivariate validated chemometric methods for the analysis of dasatinib, sorafenib, and vandetanib in pure form, dosage forms and biological fluids

New precise, responsive and selective univariate and multivariate chemometric spectrophotometric methods were developed and validated for determination of vandetanib (VTB), dasatinib (DTB), and sorafenib (SFB) in pure form, tablets, spiked human (plasma and urine). Determination of these drugs is essential because of their therapeutic benefits. These methods included double divisor ratio spectra derivative univariate method and chemometric multivariate method including partial least-squares (PLS) and principal component regression (PCR). A novel univariate method was developed for the estimation of these drugs. This method depends on the UV-Spectrophotometric data for simultaneous analysis of a ternary overlapped mixture. The Double divisor ratio spectra derivative absorption minima at 358.4 nm was used for quantification of VTB, absorption maxima at 300.3 nm for quantification of DTB and absorption maxima at 259.8 nm for quantification of SFB. This method shown a linearity in the extent of 2–9 μg/mL for VTB and DTB and over the concentration range of 3–9 μg/mL SFB within correlation coefficient (r2) of 0.9999. This method was successfully applied to pure form, tablet dosage form, spiked human (urine and plasma). Chemometric PLS and PCR models were found to be linear in the range of 2–9, 2–9, and 3–9 μg/mL for VTB, DTB and SFB, respectively. These models were estimated using eighteen mixtures as calibration set and seven mixtures as validation set. In the original data, the minimum root mean square error of prediction (RMSEP) was 0.11, 0.09 and 0.09 for VTB, DTB and SFB by PLS and 0.05, 0.04 and 0.03 by PCR while in the derivative data, the RMSEP was 0.09, 0.10 and 0.09 by PLS and 0.06, 0.06 and 0.03, by PCR for VTB, DTB and SFB, respectively. These methods were applied for the determination of the drugs in pure form and dosage form. Updating PLS model permitted the determination of the VTB, DTB and SFB in spiked human urine, plasma and drug-dissolution test of their tablet.

Development of stable amorphous solid dispersion and quantification of crystalline fraction of lopinavir by spectroscopic-chemometric methods

This study aimed to improve the dissolution of the poorly soluble drug lopinavir (LPV) by preparing amorphous solid dispersions (ASDs) using solvent evaporation method. The ASD formulations were prepared with ternary mixtures of LPV, Eudragit® E100, and microcrystalline cellulose (MCC) at various weight ratios. The ASDs were subjected to solid-state characterization and in vitro drug dissolution testing. Chemometric models based on near infrared spectroscopy (NIR) and NIR-hyperspectroscopy (NIR-H) data were developed using the partial least squares (PLS) regression and externally validated to estimate the percent of the crystalline LPV in the ASD. Initially, the solid-state characterization data of ASDs showed transformation of the drug from crystalline to amorphous. Negligible fraction of crystalline LPV was present in the ASD (3%). Compared to pure LPV, ASDs showed faster and higher drug dissolution (<2% vs. 60.3–73.5%) in the first 15 min of testing. The ASD was stable against crystallization during stability testing at 40 °C/75% for a month. In conclusion, the prepared ASD was stable against devitrification and enhance the dissolution of LPV.

Controlled-release antihistamines using supercritical antisolvent process

Antihistamines are widely used to treat allergic diseases; these drugs plasma concentration reaches a peak in a relatively short time, counteracting the allergy’s acute effects. Considering the chronicity of some symptoms, the effect of the antihistamine has to be prolonged over time; therefore, it is important to propose controlled-release systems. Supercritical Antisolvent coprecipitation is used to process cetirizine dihydrochloride and ketotifen, two antihistamines, using zein as the carrier to obtain controlled-release systems. The effect of temperature and polymer/drug ratio on the morphology and mean size of the powders is evaluated. From the UV–vis drug dissolution tests, it is possible to observe that the release of the active ingredient is significantly prolonged for both the antihistamines. Thanks to the presence of an initial burst effect, last generation formulations with bimodal releases are obtained, which allow to offer immediate relief from allergic symptoms followed by a prolonged release of the active ingredient.

Solubility enhancement of mefenamic acid by inclusion complex with β-cyclodextrin: in silico modelling, formulation, characterisation, and in vitro studies

The aim of this study was to prepare and characterise inclusion complexes of a low water-soluble drug, mefenamic acid (MA), with β-cyclodextrin (β-CD). First, the phase solubility diagram of MA in β-CD was drawn from 0 to 21 × 10−3 M of β-CD concentration. A job’s plot experiment was used to determine the stoichiometry of the MA:β-CD complex (2:1). The stability of this complex was confirmed by molecular modelling simulation. Three methods, namely solvent co-evaporation (CE), kneading (KN), and physical mixture (PM), were used to prepare the (2:1) MA:β-CD complexes. All complexes were fully characterised. The drug dissolution tests were established in simulated liquid gastric and the MA water solubility at pH 1.2 from complexes was significantly improved. The mechanism of MA released from the β-CD complexes was illustrated through a mathematical treatment. Finally, two in vitro experiments confirmed the interest to use a (2:1) MA:β-CD complex.

ESTUDO COMPARATIVO DO CONTROLE DA QUALIDADE DE COMPRIMIDOS DE NIMESULIDA COMPLEXADA E NÃO COMPLEXADA COM Β-CICLODEXTRINA

O controle da qualidade de sólidos por meio de ensaios físico-químicos apresenta grande importância na garantia da qualidade de medicamentos. Diante disto, este estudo teve como objetivo comparar a qualidade de comprimidos de nimesulida com β-ciclodextrina (Maxsulid®) e sem β-ciclodextrina (Nisulid®) como forma de investigar se os testes vigentes se aplicam às formas farmacêuticas que contenham complexos de inclusão com ciclodextrinas em sua composição. Para tal, foram realizados ensaios físico-químicos descritos na Farmacopeia Brasileira 6ª edição para comprimidos de nimesulida. Frente ao exposto, ambos os medicamentos obtiveram resultados satisfatórios na maioria dos testes de caracterização físico-química. Os testes de doseamento e dissolução foram realizados por meio de determinações quantitativas utilizando a Cromatografia Líquida de Alta Eficiência. Os resultados do doseamento mostraram que a metodologia aplicada não está adequada para extrair o fármaco do complexo de inclusão e assim doseá-lo de maneira eficiente. No teste de dissolução, os dois medicamentos foram aprovados de acordo com os critérios estabelecidos na Farmacopeia Brasileira. Porém, Maxsulid® foi o único a obter sua totalidade dissolvida em 120 minutos. Dessa forma, fica clara a importância da implementação de protocolos analíticos adequados às novas tecnologias aplicadas na produção de medicamentos.

Preparation of Ginkgolide Solid Dispersions with Low-Molecular-Weight Chitosan and Assessment of their Protective Effect on Isoproterenol- Induced Myocardial Injury.

Ginkgolides are widely used in cardio-protective therapy; however, poor bioavailability currently limits their application. The purpose of this study was to demonstrate whether solid dispersions prepared with Low- Molecular-Weight Chitosan (LMWC) could improve the protective effect of ginkgolides on Myocardial Injury (MI). Ginkgolide Solid Dispersions (GKSD) were prepared with LMWC. Their properties were then characterized using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy. In vivo pharmacokinetic studies were performed in rats, and the protective effect of GKSD on MI was investigated by western blotting and immunohistochemical analyses. Drug dissolution testing showed that GDSD were released at a significantly higher rate than ginkgolides, dissolved by alternative methods, suggesting that LMWC facilitates the release of ginkgolides. Differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy all showed that GKSD was amorphous. In-vivo testing revealed larger AUC0-t, higher Cmax, and shorter Tmax for GKSD compared to that in original ginkgolides. Myocardial injury was induced in rats with isoproterenol to test the protective effect of GKSD. GKSD alleviated MI and reduced myocardial fibrosis, as observed by Hematoxylin and Eosin staining. Compared with the crude drug group, the secretion of malonyl dialdehyde and nitric oxide and expression of NOX-2 and NOX-4 were lower. The activities of the cardiac marker enzymes SOD, CAT, GPX, GPX-1, and GSH were higher in GKSD-administered rats, indicating a beneficial effect of GKSD in eliminating free radicals during myocardial injury. Additionally, western blotting and immunohistochemical analysis showed that GKSD markedly reduced the expression of signaling proteins RHOA, ROCK1, ROCK2, and RAC1. Solid dispersions prepared with low molecular weight chitosan improved the oral bioavailability of ginkgolide and enhanced its protective effect on myocardial injury.

On-line dissolution analysis of multiple drugs encapsulated in electrospun nanofibers.

Electrospun nanofiber is a very attractive material which can be used as the support to form multiple-drug dosage. Understanding the dissolution process of different active drug ingredients released from electrospun fibers is of great importance to control and evaluate the quality of medicated nanofibers. Here we present the first study of on-line automatic analysis of dissolution of multiple drugs in electrospun fiber mats. Single-needle electrospinning technology is utilized to combine polymers, hydrophilic polyvinylpyrrolidone (PVP) and hydrophobic polycaprolactone (PCL) as carrier to load three poorly water-soluble non-steroidal anti-inflammatory drugs (paracetamol, nimesulide, and ibuprofen). The loading of the drugs in PVP/PCL electrospun fibers are characterized by various techniques, including scanning electron microscopy, X-ray diffraction, Fourier infrared spectroscopy and differential scanning calorimetry. The in vitro dissolution is investigated by our home-made portable analyzer, which can simultaneously on-line determine multiple drugs released from the nanofibers by a single step. The analysis shows a wide linear detection range of the drugs with limit-of-detection (LOD) down to μg/mL-level. The dissolution profiles of three ingredients in nanofibers can be monitored every thirty seconds from the beginning to the end in the entire dissolution process from only one HSCE run. The kinetic information of the dissolution, including the dissolution curve, characteristic dissolution time and dissolution efficiency, is obtained and evaluated for different dissolution media, drug loading content and the ratio of PVP/PCL. Our study provides a promising method for rapid and accurate dissolution testing of nanofiber-based drugs, and would extend the applications of separation techniques in pharmaceutical analysis.

Portable and automated analyzer for rapid and high precision in vitro dissolution of drugs

We developed a novel portable and automated dissolution test analyzer for rapid and high precision in vitro dissolution testing of drugs. The analyzer consists of a flow-through-cell drug dissolution system, an automated sequential sampling system, a high-speed capillary electrophoresis (HSCE) system, and a data acquisition system. Combining the high-temporal resolution flow-gating sampling approach with HSCE, which has outstanding advantages of efficient separation and resolution, the analyzer can achieve rapid analysis and exhibits the ability in miniaturization for on-site assessment of different active pharmaceutical ingredients. To integrate the flow-through-cell dissolution system with HSCE, a specially designed flow-gating-injection (FGI) interface was employed. The performance of the analyzer was investigated by analyzing the dissolution of immediate-release drugs including single dose (amoxicillin dispersible tablets) and fixed dose combination (amoxicillin and clavulanate potassium) drug tablets with the high-temporal resolutions of 12 s and 20 s, respectively. The dissolution profiles of different active pharmaceutical ingredients could be simultaneously and automatically monitored with high repeatability and accuracy. The analyzer was successfully utilized for the pharmaceutical quality control and bio-relevant dissolution testing, as well as in vivo-in vitro correlation analysis. Our portable analyzer is miniaturized, convenient and of low-cost, and will provide a valuable tool for dissolution testing in pharmaceutical research and development.

Continuous synthesis of drug nanocrystals by solid hollow fiber cooling crystallization.

Size reduction of drug with poor water solubility to nanoscale is an effective way to help improve the efficacy of drug delivery to the human body. A solid hollow fiber cooling crystallization technique has been adopted to continuously produce griseofulvin drug nanoparticles under modest conditions with accurate controllability. In the solid hollow fiber cooling crystallization device, drug solution flowed through the bores of solid hollow fibers while the cooling liquid was circulated counter-currently in the shell side of the device to cool down the drug solution in the tube side. Due to intense heat exchange between the cooling liquid and the drug solution through the thin fiber walls, the temperature of drug solution decreased rapidly so that drug nanoparticles were precipitated out from the solution by sudden reduction of solubility. Through variation of the experimental conditions and parameters, the mean size of the produced nanoparticles was regulated and controlled. The nanoparticles were dispersed uniformly, the chemical structure and bonds of prepared nanoparticles was the same with as-received griseofulvin. Both raw material and NPs the polymorph(s) present form I, the melting point was 220 °C. Drug dissolution testing was also executed to verify that nanocrystals have a higher dissolution profile.

Automatic Dissolution Testing with High-Temporal Resolution for Both Immediate-Release and Fixed-Combination Drug Tablets

Dissolution testing plays many important roles throughout the pharmaceutical industry, from the research and development of drug products to the control and evaluation of drug quality. However, it is a challenging task to perform both high-efficient separation and high-temporal detection to achieve accurate dissolution profile of each active ingredient dissolved from a drug tablet. In our study, we report a novel non-manual-operation method for performing the automatic dissolution testing of drug tablets, by combining a program-controlled sequential analysis and high-speed capillary electrophoresis for efficient separation of active ingredients. The feasibility of the method for dissolution testing of real drug tablets as well as the performance of the proposed system has been demonstrated. The accuracy of drug dissolution testing is ensured by the excellent repeatability of the sequential analysis, as well as the similarity of the evaluation of dissolution testing. Our study show that the proposed method is capable to achieve simultaneous dissolution testing of multiple ingredients, and the matrix interferences can be avoided. Therefore it is of potential valuable applications in various fields of pharmaceutical research and drug regulation.

Compatibility study of hydroxychloroquine sulfate with pharmaceutical excipients using thermal and nonthermal techniques for the development of hard capsules

Hydroxychloroquine is effectively used in the treatment for malaria, lupus erythematosus and rheumatoid arthritis. The study of drug–excipient compatibility is an important tool for the development of safe and effective pharmaceutical forms. The present study describes the use of thermal and nonthermal techniques for evaluating the physicochemical compatibility of hydroxychloroquine with excipients for the development of solid dosage forms, including microcrystalline cellulose, corn starch, mannitol, magnesium stearate and colloidal silicon dioxide. The analytical techniques employed to evaluate the drug and the drug–excipient interactions in solid binary mixtures (1:1 w:w) were differential scanning calorimetry (DSC), thermogravimetry, Fourier transform infrared spectroscopy (FTIR) and isothermal stress test. Four different formulations were prepared and drug dissolution test was determined by rotating-basket system method in water. Evidence of solid-state interactions of hydroxychloroquine and mannitol, magnesium stearate and colloidal silicon dioxide was observed in the DSC analysis and subsequently confirmed by FTIR; however, no degradation profile was observed by HPLC and no interference was seen in the drug dissolution rate and no change in physicochemical properties of hydroxychloroquine was observed. The combination of techniques is very important to correctly identify drug–excipients incompatibilities in the earliest stage of a formulation design in order to ensure the choice of suitable excipients for the development of stable and effective dosage forms of hydroxychloroquine.