Dissolution Apparatus Research Articles

Self-Nanoemulsifying Drug Delivery System Combined with a Polymeric Amorphous System of Glibenclamide for Enhanced Drug Dissolution and Stability.

Self-nanoemulsifying drug delivery systems (SNEDDS) have been widely applied to improve the dissolution and bioavailability of hydrophobic medications like glibenclamide (GB). However, the acid liability of GB limits its loading in SNEDDS formulation owing to the expected drug degradation. The present study investigated the ability of a polymeric amorphous system (PAS) to amorphize raw GB and facilitate its integration within dispersed SNEDDS. Liquid-SNEDDS (L-SNEDDS), solid-SNEDDS (S-SNEDDS), and combined systems (SNEDDS + PAS) were prepared for this purpose. The physicochemical properties of the prepared formulations were examined using a zeta-sizer, SEM, DSC, PXRD, and dissolution apparatus. In addition, GB integrity within formulations following incubation in a stability chamber was also investigated. The prepared formulations were able to be dispersed within the nanosize range. SEM, DSC, and PXRD showed that freeze-drying (FD) was superior to the microwave (MW) method in GB amorphization. Even though L-SNEDDS and S-SNEDDS were able to increase the dissolution efficiency (DE) of GB, drug degradation was observed. However, PAS prepared using FD was able to increase the DE of GB from 2.5% to 84.2% and protect the drug from chemical degradation. The present study revealed that a combined system (SNEDDS + PAS) is a promising approach to enhance the stability of acid-labile drugs and facilitate the integration of amorphous drugs within a dispersed SNEDDS formulation.

Investigations on the Impacts of Drugs or Excipients with Different Physicochemical and Compaction Properties on the Disintegration Behavior of Kollidon®SR-Based Binary Controlled Release Matrix Tablets.

The objective of this study was to examine the impact of the physicochemical properties of the loaded drug or excipient, the concentration of Kollidon®SR (KSR), and the mechanical characteristics of KSR compacts on their disintegration times. Using disintegration apparatus, a two-hour constraint was chosen as the process's end point. Lactose-KSR compacts subjected to the highest compression pressure and Microcrystalline cellulose-KSR compacts with KSR concentrations exceeding 30% exhibited disintegration times of less than ten minutes. Likewise, compacts containing Diltiazem HCl-KSR demonstrated brief disintegration times across all tested KSR concentrations and compression pressures. Compacts of Modafinil, Metformin HCl, and Ascorbic acid-KSR displayed disintegration times ranging from fast to moderate, contingent upon the levels of KSR and compression pressure applied. Compacts containing KSR with Aspirin, Salicylic acid, or Ibuprofen did not exhibit significant disintegration even at minimal amounts of KSR (0.5%). Theophylline-KSR tablets also showed prolonged dissolution times, even at very low concentrations of KSR. The disintegration times of Dic-KSR tablets were roughly close to an hour and were predominantly unaffected by varying KSR levels and only marginally influenced by compression pressures. It is possible to draw the conclusion that different drugs or excipients have different minimum KSR requirements to resist compacts' disintegration process. Compounds that demonstrate low solubility in water can result in extended disintegration times for KSR compacts. The melting points of these compounds, in conjunction with the Py values of the compacts and their compaction properties, could affect the disintegration process, although a precise evaluation is necessary.

Interaction of 6-Thioguanine with Aluminum Metal-Organic Framework Assisted by Mechano-Chemistry, In Vitro Delayed Drug Release, and Time-Dependent Toxicity to Leukemia Cells.

6-thioguanine (6-TG) is an antimetabolite drug of purine structure, approved by the FDA for the treatment of acute myeloid lesukemia, and it is of interest in treating other diseases. The interaction of drugs with matrices is of interest to achieving a delayed, sustained, and local release. The interaction of 6-TG with an aluminum metal-organic framework (Al-MOF) DUT-4 is studied using a novel experimental approach, namely, mechano-chemistry by liquid-assisted grinding (LAG). The bonding of 6-TG to the DUT-4 matrix in the composite (6-TG)(DUT-4) was studied using ATR-FTIR spectroscopy and XRD. This interaction involves amino groups and C and N atoms of the heterocyclic ring of 6-TG, as well as the carboxylate COO- and (Al)O-H groups of the matrix, indicating the formation of the complex. Next, an in vitro delayed release of 6-TG was studied from composite powder versus pure 6-TG in phosphate buffered saline (PBS) at 37 °C. Herein, an automated drug dissolution apparatus with an autosampler was utilized, and the molar concentration of the released 6-TG was determined using an HPLC-UV analysis. Pure 6-TG shows a quick (<300 min) dissolution, while the composite gives the dissolution of non-bonded 6-TG, followed by a significantly (factor 6) slower release of the bonded drug. Each step of the release follows the kinetic pseudo-first-order rate law with distinct rate constants. Then, a pharmaceutical shaped body was prepared from the composite, and it yields a significantly delayed release of 6-TG for up to 10 days; a sustained release is observed with the 6-TG concentration being within the therapeutically relevant window. Finally, the composite shows a time-dependent (up to 9 days) stronger inhibition of leukemia MV-4-11 cell colonies than 6-TG.

The Milling Method in Formation of Inclusion Complex p-Methoxycinnamic Acid-Hydroxypropyl-β-Cyclodextrin.

p-methoxycinnamic acid (pMCA) is a substance with several pharmacological activities, derived from the rhizome of Kaempferia galanga Linn. The solubility of pMCA can be increased by the formation of inclusion complexes (IC) using hydroxypropyl-βcyclodextrin (HPβCD) compounds. IC are obtained through the milling method, which is a simple, environmentally friendly, and low-cost manufacturing method. The process involves the pounding of material with a certain speed and impact force. This research aims to characterize the pMCA-HPβCD IC made using the milling method. Milling the mixture of pMCA and HPβCD using a ball mill is a common technique to enhance the formation of the inclusion complex. The IC’s physical characteristics were analyzed in terms of their morphology, particle size, crystallinity, and thermal properties. The dissolution profile was also performed using paddle-typed dissolution apparatus (Type II) with 500 mL distilled water as dissolution medium. The amount of pMCA dissolved was determined using UV spectrophotometry. The dissolution parameter was determined as dissolution efficiency at 60 minutes (DE60). The IC particles were irregular in shapes and porous. The size was reduced as compared to the individual components. The XRD revealed that the ICs were amorphous. The DE60 of IC increased by a factor of 4.3 compared to the pure pMCA. In conclusion, the milling method successfully formed complex of pMCA-HPβCD with different characteristics from the initial compound and was significantly increased the percentage of the dissolved pMCA.

QBD approach for green synthesis of Rutin silver nanoparticles- screening for antioxidant, anticancer and anticlastogenic potential

Rutin is a flavonoid glycoside abundant in many plants exhibiting pharmacological activities like antioxidant, anticancer, anti-inflammatory and antimicrobial activities. Plant biomarkers suffer low bioavailability and solubility that lack clinical effectiveness. The smart nanoparticles conversion addresses this limitation with optimal particle size and targeted drug delivery. The present study involves QbD approach for formulation of Rutin silver nanoparticles and evaluation of antioxidant, anticancer and anticlastogenic potential. QbD experimentation involved particle size and drug release as dependent variables over the silver nitrate concentration, methanol and sonication time as independent variables devising 15 formulations (F1 –F15). F12 formulation was found to be optimized with 126.3 nm average size, stable and dispersible characterized by UV, FTIR, SEM and DLS studies. The calibration curve of Rutin was plotted at 352 nm with linearity (LOD = 0.061 μg/ml and LOQ = 0.187 μg/ml). The invitro drug release studies by USP dissolution apparatus I (Basket type) proved the sustained release characteristics with 97.3 % drug release when compared to the Rutin. The pharmacological screening for potential antioxidant and anticancer activity on G361 and MCF 7 cell line of F12 formulation have shown promising results and also enhanced solubility in water compared to Rutin. Anticalstogenic potential as a function of induced micronuclei frequency was evaluated as a characteristic feature in bone marrow cells obtained from mice. Results indicate pre-treatment with the F12 reduced frequency of micronuclei in mouse bone marrow cells caused by Cyclophosphamide (CP) significantly. The protective effect of F12 in suppression was demonstrated at both dosages of 100 and 200 mg/kg. Thus the findings suggest the novel Rutin silver nanoparticles as lead drug serving as antioxidant, anticancer and anticlastogenic agent.

Comparative in-Vitro dissolution study of some sitagliptin generic tablets under biowaiver conditions by UV-Spectroscopy

The objective of this study is to evaluate the bioequivalence of generic sitagliptin tablets from different manufacturers using in-vitro dissolution study under biowaiver conditions through UV Spectroscopy, and compare them with the innovator brand. The dissolution media consisted of three different buffers with varying pH levels, including HCl Buffer pH 2.0, Phosphate Buffer pH 4.0, and Phosphate Buffer pH 7.2. The dissolution process was conducted using a USP type-2 dissolution apparatus with a 900 ml basket. The rotational speed of the paddle was set at 50 RPM, while maintaining a temperature of 37.5°C +/- 2°C. Samples were collected at four different intervals as recommended by the USFDA, which were 15, 30, 45, and 60 minutes. Validation parameters such as Accuracy, Precision, Linearity, LOD, and LOQ were assessed. The dissolution profiles exhibited no significant variability between different brands and within the same brand. Furthermore, the dissolution results of all tablet formulations, including the innovator brand, were analysed using the difference factor (f1) and similarity factor (f2). The findings from this study indicate that both generic brands of sitagliptin tablets meet the USFDA dissolution specifications and can be considered interchangeable.

Disintegration characteristics and mechanism of red clay improved by steel slag powder

Red clay is prone to softening and disintegration when exposed to water, often triggering severe geological disasters. To enhance its resistance to disintegration, this paper employs a homemade wet-dry cycling disintegration apparatus, combined with XRD, SEM, MIP, and fractal theory, to analyze the effects of different activators on the disintegration characteristics and microscopic mechanisms of SSP-improved soil. Under wet-dry cycling, the disintegration process of SSP-improved soil can be divided into five stages: rapid water absorption, saturation wetting, rapid disintegration, softening and dissolution, and stable non-disintegration. As the activator and SSP content increase, the resistance to disintegration of SSP-improved soil gradually enhances. After the addition of activators, the porosity, pore area, pore length and width, and probability entropy of SSP-improved soil decrease (i.e., 7 % NS < 7 % CSW < 7 % NH < undisturbed soil), while the average shape factor, regional probability distribution index, and fractal dimension increase. This is because activators promote ion exchange, cementation, crystallization, and carbonation reactions in SSP-improved soil, generating a substantial amount of hydration products such as C-S(A)-H, Ca(OH)2 and CaCO3, which fill and encapsulate inter-particle pores, thereby reducing water flow channels within the pores. In contrast, the pore structure between particles in undisturbed soil is simple and well-connected, providing favorable conditions for the migration and dissolution of fine particles and the loss of cementing materials, which accelerates the destruction and disintegration of the soil structure.

Unleashing the Potential of β -cyclodextrin Inclusion Complexes in Bitter Taste Abatement: Development, Optimization and Evaluation of Taste Masked Anti-emetic Chewing Gum of Promethazine Hydrochloride.

Motion sickness also known as kinetosis is a condition in which there exists a disagreement between visually perceived movement and the vestibular system's sense of movement. Nausea, vomiting, dizziness, fatigue, and headache are the most common symptoms of motion sickness. This study mainly focuses on the taste masking of Promethazine Hydrochloride (PMZ) by inclusion complexation method, its formulation development in the chewing gum form by using directly compressible gum base HIG® and its quality and performance testing. Different molar ratios (1:1, 1:2, 1:3 and 1:4) of PMZ-cyclodextrin complexes were prepared by using β-Cyclodextrin(β-CD) as a taste masking agent. These complexes were evaluated for FTIR, DSC, % Entrapment Efficiency, % drug yield, and taste evaluation by E-Tongue. The optimized ratio was further evaluated by sophisticated analytical techniques such as Scanning Electron Microscopy (SEM) and X-Ray Diffraction (XRD). A central composite design (CCD) (3 ^2) was utilized to examine the effects of independent variables (amount of gum-X1 and amount of plasticizer-X2) on dependent variables (%CDRY1 and hardness Y2). The prepared gums were evaluated for drug content, organoleptic properties, in-vitro dissolution testing by fabricated disintegration apparatus, texture analysis, etc. The optimization statistics showed that on decreasing the amount of gum, in- vitro drug release increases and hardness decreases. The optimized batch MCG-2 of Promethazine MCG showed 92.34 ± 0.92% of drug release, whereas for marketed formulation (Phenergan®-25mg) drug release value was 86.19 ± 1.88%. Results provided evidence that PMZ MCGs could be a better alternative to conventional tablet formulations with improved drug release, palatability and texture.

Encapsulation of Gemcitabine on Porphyrin Aluminum Metal-Organic Framework by Mechano-Chemistry, Delayed Drug Release and Cytotoxicity to Pancreatic Cancer PANC-1 Cells.

Gemcitabine is a widely used antimetabolite drug of pyrimidine structure, which can exist as a free-base molecular form (Gem). The encapsulated forms of medicinal drugs are of interest for delayed and local drug release. We utilized, for the first time, a novel approach of mechano-chemistry by liquid-assisted grinding (LAG) to encapsulate Gem on a "matrix" of porphyrin aluminum metal-organic framework Al-MOF-TCPPH2 (compound 2). The chemical bonding of Gem to compound 2 was studied by ATR-FTIR spectroscopy and powder XRD. The interaction involves the C=O group of Gem molecules, which indicates the formation of the encapsulation complex in the obtained composite. Further, the delayed release of Gem from the composite was studied to phosphate buffered saline (PBS) at 37 °C using an automated drug dissolution apparatus equipped with an autosampler. The concentration of the released drug was determined by HPLC-UV analysis. The composite shows delayed release of Gem due to the bonded form and constant concentration thereafter, while pure Gem shows quick dissolution in less than 45 min. Delayed release of Gem drug from the composite follows the kinetic pseudo-first-order rate law. Further, for the first time, the mechanism of delayed release of Gem was assessed by the variable stirring speed of drug release media, and kinetic rate constant k was found to decrease when stirring speed is decreased (diffusion control). Finally, the prolonged time scale of toxicity of Gem to pancreatic cancer PANC-1 cells was studied by continuous measurements of proliferation (growth) for 6 days, using the xCELLigence real-time cell analyzer (RTCA), for the composite vs. pure drug, and their differences indicate delayed drug release. Aluminum metal-organic frameworks are new and promising materials for the encapsulation of gemcitabine and related small-molecule antimetabolites for controlled delayed drug release and potential use in drug-eluting implants.

Evaluation of Dissolution Release Profiles of Nicotine and Three Distinct Flavor Markers in Loose Moist Smokeless Tobacco Products

Summary This study describes the dissolution release profiles of nicotine and flavor markers from three loose moist smoke-less tobacco (MST) products, same brand, each made with a distinct flavor. The US Pharmacopeia flow-through cell dissolution apparatus 4 (USP-4) was employed, following a previously published method that was validated to study the nicotine release from MST products. Herein, we expanded the scope of the analytical method by incorporating three flavor markers including methyl salicylate, ethyl salicylate, and glycyrrhizic acid to provide an understanding of the dissolution release profiles of not only nicotine but also of flavor markers. The dissolution release profiles of nicotine were found to be equivalent across all three tobacco products. In contrast, the release profiles of the studied flavor markers exhibited distinct differences, primarily influenced by their chemical properties, particularly polarity. Notably, glycyrrhizic acid demonstrated the most rapid release rate, while ethyl salicylate exhibited the slowest release rate. This study serves as a valuable resource for researchers, manufacturers, and regulatory bodies involved in the evaluation of MST products attributes and performance.

Transethosomal Carrier of Curcumin for Improved Topical Delivery: Optimization, In-vitro and Stability Assessment

Objective:: Currently, there is a clear lack of effective topical treatments for psoriasis. In light of this unaddressed requirement, the work intends to develop, enhance, and assess the effectiveness of a curcumin transethosomal gel for managing psoriasis. This work signifies the delivery of a potential solution to fill the gap in topical psoriasis treatment. Material and Methods:: Curcumin-loaded transethosomes were prepared using a mechanical dispersion method. An initial study was conducted to determine the ideal concentrations of Lipoid S100 and Isopropyl Myristate (IPM). To refine the ultimate transethosomal formulation, a full factorial design (32) was employed, incorporating different levels of Lipoid S100 and IPM. Drug release investigations and pharmacokinetics assessments of curcumin concentrations were performed using a specialized dissolution apparatus and an animal model, respectively. Results:: The characterization profile and analytical examinations have affirmed the stability of the formulation throughout the study duration. Our findings indicate that the drug release mechanism conforms to a diffusion pattern akin to Fickian transport. Furthermore, In-vivo investigations revealed that the curcumin concentration in the bloodstream after oral administration was significantly superior to that of the conventional formulation. Conclusion:: Using curcumin-loaded transethosomes extends drug contact time and facilitates controlled drug release, leading to enhanced bioavailability, decreased dosage needs, and heightened patient safety.

The impact of sinkers on coning issues exhibited by tablets in USP2 dissolution apparatus

The objective of this research is to explore the impact of sinkers on the dissolution rate of tablets exhibiting coning in paddle dissolution tests. The ICH M9 guideline refers to the use of sinkers to mitigate coning issues. However, the effectiveness of sinkers on coning phenomena has not been comprehensively investigated. Therefore, this study evaluated whether applying sinkers of different shapes could alleviate coning problems. The dissolution profiles of amlodipine tablet formulations which had been clinically demonstrated to be bioequivalent were assessed in a USP2 Apparatus with and without sinkers. Moreover, the effects of artificially induced coning formed by adding cellulose particles of various sizes on dissolution profiles, and the impacts of sinkers on the dissolution delay caused by the cellulose particles were investigated. Our study suggested that the CLIPS sinker was effective in obtaining in vivo relevant dissolution profiles by facilitating the dispersion of coning. The effect of sinkers varied depending on their shapes and the characteristics of the particles that constituted the coning. These findings enhance our understanding of the effectiveness of sinkers in addressing coning issues and aid in predicting the in vivo dissolution performance of tablet formulations that exhibit coning during dissolution testing.

Bioequivalence prediction with small-scale biphasic dissolution and simultaneous dissolution-permeation apparatus—An aripiprazole case study

Both biphasic dissolution and simultaneous dissolution-permeation (D-P) systems have great potential to improve the in vitro-in vivo correlation compared to simple dissolution assays, but the assay conditions, and the evaluation methods still need to be refined in order to effectively use these apparatuses in drug development.Therefore, this comprehensive study aimed to compare the predictive accuracy of small-volume (16–20 mL) D-P system and small-volume (40–80 mL) biphasic dissolution apparatus in bioequivalence prediction of five aripiprazole (ARP) containing marketed drug products.Assay conditions, specifically dose dependence were studied to overcome the limitations of both small-scale systems. In case of biphasic dissolution the in vivo maximum plasma concentration (Cmax) prediction greatly improved with the dose reduction of ARP, while in case of the D-P setup the use of whole tablet gave just as accurate prediction as the scaled dose. With the dose reduction strategy both equipment was able to reach 100 % accuracy in bioequivalence prediction for Cmax ratio. In case of the in vivo area under the curve (AUC) prediction the predictive accuracy for the AUC ratio was not dependent on the dose, and both apparatus had a 100 % accuracy predicting bioequivalence based on AUC results.This paper presents for the first time that not only selected parameters of flux assays (like permeability, initial flux, AUC value) were used as an input parameter of a mechanistic model (gastrointestinal unified theory) to predict absorption rate but the whole in vitro flux profile was used. All fraction absorbed values estimated by Predictor Software fell within the ±15 % acceptance range during the comparison with the in vivo data.

Study on Mudcake disintegration in clayey strata during shield tunneling: Effects of dispersants and bentonite slurry

While tunnel boring machines (TBMs) tunneling in clayey strata, the adhered excavated soil on the cutterhead and cutting tools tends to form mudcake after compaction and consolidation. Mudcake can obstruct the cutterhead openings and rendering the cutting tools ineffective, leads to a substantial reduction in advance rate. Dispersants are recognized as an effective method for the disintegration of mudcakes. A novel set of equipment, comprising a mudcake compression device and a mudcake disintegration apparatus, is developed for assessing mudcake disintegration properties. The results showed that mudcakes underwent a tripartite disintegration process in water, including an initial stage, a rapid disintegration stage, and a stable stage. In the initial stage, the mudcakes absorbed water before disintegration, resulting in marginal changes in the weight of the disintegrated mudcakes. In the rapid disintegration stage, the weight of the disintegrated mudcakes increased quickly. During the stable stage, the weight of the disintegrated mudcakes remained relatively constant. The submersion of mudcakes in a dispersant solution substantially increased the rate of disintegration. Greater dispersant concentration corresponded to an increase in the disintegration rate. No weight gain was observed in mudcakes during the initial disintegration stage. When mudcakes disintegrated in a bentonite slurry, the weight of the disintegrated mudcakes initially decreased and then stabilized. The weight of the disintegrated mudcakes turned negative, indicating an increase in the weight of mudcakes. This suggested that bentonite significantly hindered mudcake disintegration.

Study on the Influence of Moisture Content and Void Ratio on the Disintegration of Red Clay

Guilin is a famous karst area, and currently the view that the disintegration of red clay will cause soil cave collapse is increasingly recognized. In order to study the influence of the coupling effect of moisture content and void ratio on the disintegration of red clay, different moisture contents and void ratios of Guilin red clay were placed on a self-made disintegration apparatus to record the real-time disintegration amount and observe the disintegration phenomenon. Images of the structural characteristics of soil were obtained by a scanning electron microscope (SEM). Additionally, nuclear magnetic resonance (NMR) was applied to analyze the distribution of water in both natural and saturated states. The results show that the disintegration rate of red clay decreases as the initial moisture content increases, but increases with the increase of void ratio. Both moisture content and void ratio affect the structural characteristics of red clay. When the moisture content remains constant, the soil changes from a three-peak to a two-peak structure as the void ratio increases. The total area and secondary peak area of the T2 spectrum increase, while the starting T2 value of the main peak shifts to the right and the area decreases. Meanwhile, the starting T2 value of the secondary peak shifts to the right and the area increases. When the void ratio remains constant, the starting T2 value of the main peak gradually shifts to the left and the area decreases as the moisture content increases. However, the starting T2 value of the secondary peak shifts to the right and the area decreases or first decreases and then increases. The disintegration rate does not exhibit a significant relationship with either pore volume or macropore volume. The combined water saturation shows a bilinear relationship with both the moisture content and void ratio, where it increases as the initial moisture content increases, but decreases as the void ratio increases, with a correlation coefficient of 0.9929. The disintegration rate has an exponential relationship with the combined water saturation, and it decreases as the combined water saturation increases, with a correlation coefficient of 0.9934.

Colon-targeted 3D-Printed mesalamine tablets: Core-shell design and in vitro/ex-vivo evaluation

ObjectivesThe present study is intended to develop a shell-core tablet using a hot melt extrusion (HME)-based dual-nozzle fused deposition modeling (FDM) three-dimensional (3D) printing approach. The primary objective was to establish a sustained-release colonic drug delivery system and improve mesalamine's permeability by incorporating Vitamin E TPGS as a permeation enhancer. MethodThe study utilized Kollidon® SR for sustained release, L-100, and HPMC HME L100 for the tablet's protective shell. Six filament formulations were tested, and the mechanical properties of the shell filaments, including the three-point bending, Hooke's law, and stiffness, were assessed. Drug release profiles of the tablets were evaluated using the USP-II dissolution apparatus, and permeability characteristics were gauged using the non-everted intestinal sac method. Solutions containing 5% w/v mesalamine and 2.5% w/v Vitamin E TPGS were employed, with pure mesalamine as a control. ResultsOptimal filament ratios were identified as 50:50 for the core and 30:70 for Eudragit L-100 to HPMC HME L100 for the shell. The resulting tablets achieved a prolonged drug release of up to 24 h for the core. They ensured minimal drug release in the upper gastrointestinal tract (∼5% in the first 5 h), effectively targeting the colon. Incorporating Vitamin E TPGS led to a 3.6-fold increase in mesalamine absorption compared to the control, and the addition of Kollidon® SR notably improved the flow properties of Mesalamine powder. ConclusionIn conclusion, this innovative approach has the potential to achieve a colon-specific drug delivery system.

Spectroscopic Monitoring and Modeling Drug Dissolution for Undergraduate Chemistry Curriculum.

The pharmaceutical and medicine manufacturing industry has become the largest industrial sector for the employment of chemists, indicating a need for experiments with a pharmaceutical sciences context in the undergraduate chemistry curriculum. In the pharmaceutical industry, testing drug dissolution is a key analytical task for solid oral dosage forms that is performed in different phases of drug development to test the release behavior of new formulations, ensure consistency between manufacturing lots, and help predict the in vivo absorption of the drug substance after administration. However, there are a limited number of laboratory experiments in dissolution testing developed for the undergraduate chemistry curriculum. To help students obtain hands-on experience in dissolution testing, a protocol has been developed for an undergraduate chemistry laboratory course for students to build a dissolution apparatus, monitor dissolution processes, model the dissolution to extract kinetic parameters, and evaluate the consistency between dissolution curves with FDA regulated methods. Students successfully collected dissolution curves and completed the modeling analysis with nonlinear least-squares fitting. The designed dissolution protocol has been evaluated to have consistency and reproducibility to be implemented in the undergraduate chemistry laboratory curriculum.

Application of the variability budget approach to the Dissolution test

The aim. This study aimed to evaluate the completeness of our knowledge about the sources of variation in the Dissolution test with 100 % release by compiling a variability budget.&#x0D; Materials and methods. The study was performed on 500 mg metformin tablets, using pharmacopoeial quality reagents, State Pharmacopoeia of Ukraine (SPhU) Metformin HCl reference standard, Pharmatest DT70 Dissolution apparatus, Perkin Elmer Lambda 35 spectrophotometer, Mettler Toledo XP 204 analytical balance, and ISO class A volumetric glassware. The SPhU metrological approach was employed.&#x0D; Results and discussion. The variability budget was compiled based on the comparison of uncertainty estimates obtained from the requirements for maximum permissible variation in normal analytical practice (UNAP, bottom-up estimation) and experimental data (Uexp). This involved characterizing Metformin content in tablets using the Uniformity of Dosage Units (UDU) test as an independent method. The 100 % release of Metformin in the Dissolution test (infinity point) was proved by increasing the dissolution time. Having optimized Dissolution and UDU analytical procedures for variability budget compiling, we achieved insignificance of Uexp compared to the target uncertainty (Utg) for the Dissolution test in compliance testing. The differences in UDU and Dissolution mean results did not exceed UNAP for the release time of 45 and 60 min, i.e. uncertainty budget was proven. Uexp for the Dissolution test indicated the presence of an unknown statistically significant source of random variation, which, however, was less than Utg; therefore, the procedure is suitable for compliance testing.&#x0D; Conclusion. Experimental results confirmed the completeness of our knowledge about sources of variation (absence of bias) for the Dissolution test with 100 % release. An essential condition for compiling the budget was the optimization of uncertainty of analytical procedures. For UDU, all significant sources of variation were within the expected range. Yet, there is a need for additional research to identify and manage an unknown source of practically significant random variation for the Dissolution test

TENOXICAM-TROMETHAMINE MULTICOMPONENT CRYSTAL: PHYSICOCHEMICAL CHARACTERISTICS, SOLUBILITY, AND DISSOLUTION EVALUATION

Objective: Tenoxicam is classified as a nonsteroidal anti-inflammatory drug employed for managing musculoskeletal conditions. However, its effectiveness is obstructed by its restricted ability to dissolve in water. This investigation aims to create a multicomponent crystal involving tenoxicam and tromethamine to augment tenoxicam's solubility and dissolution rate.&#x0D; Methods: Using the solvent drop grinding technique, the multicomponent crystal was synthesized by combining tenoxicam and tromethamine in equimolar proportions. The physicochemical properties of multicomponent crystal were assessed through powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and FT-IR spectroscopy. Solubility test and dissolution rate profile were conducted to evaluate the effectiveness of multicomponent crystal formation in compared to intact tenoxicam. The solubility test occurred in CO2-free distilled water over 48 h and was quantified using UV spectrophotometry at 368 nm. Dissolution rate profiles were conducted using a USP type II dissolution apparatus in HCl 0.1 N, and CO2-free distilled water as the dissolution media.&#x0D; Results: The multicomponent crystal displayed distinctive characteristics in the diffractogram, including altered melting points, and shifts in the FT-IR spectrum peaks. Within the multicomponent crystal system, the solubility of tenoxicam exhibited a notable increase, specifically by a factor of 11.130. Moreover, the dissolution efficiency of tenoxicam in HCl 0.1 N solution and CO2-free distilled water showed substantial enhancements, with respective increases of 2.600-fold and 8.605-fold observed at the 60-minute mark.&#x0D; Conclusion: In conclusion, the tenoxicam and tromethamine multicomponent crystal formation using a solvent drop grinding technique resulted in a novel crystalline structure, enhancing the solubility and dissolution of tenoxicam both in CO2-free distilled water and HCl 0.1 N.

Development of multiple structured extended release tablets via hot melt extrusion and dual-nozzle fused deposition modeling 3D printing

The study aims to fabricate extended release (ER) tablets using a dual-nozzle fused deposition modeling (FDM) three-dimensional (3D) printing technology based on hot melt extrusion (HME), using caffeine as the model compound. Three different ER tablets were developed, which obtained “delayed-release”, “rapid-sustained release”, and “release-lag-release” properties. Each type of tablet was printed with two different formulations. A novel printing method was employed in this study, which is to push the HME filament from behind with polylactic acid (PLA) to prevent sample damage by gears during the printing process. Powder X-ray diffractometry (PXRD) and differential scanning calorimetry (DSC) results showed that caffeine was predominately amorphous in the final tablets. The dissolution of 3D printed tablets was assessed using a USP-II dissolution apparatus. ER tablets containing PVA dissolved faster than those developed with Kollicoat IR. Overall, this study revealed that ER tablets were successfully manufactured through HME paired with dual-nozzle FDM 3D printing and demonstrated the power of 3D printing in developing multi-layer tablets with complex structures.