Similar Dissolution Profiles Research Articles

Enhancing Albendazole Delivery Using Mesoporous Santa Barbara Amorphous‐15: A Box‐Behnken Design Study

Over 70% of pharmaceutical compounds face the challenge of poor water solubility, which impacts on their bioavailability. This study focuses on the use of Santa Barbara Amorphous‐15 (SBA‐15) mesoporous silica material as carrier, which is synthesized and characterized to address this limitation. Albendazole (ABZ), an antiparasitic agent with low water solubility, serves as model drug. A Box‐Behnken design (BBD) is used to investigate the impact of immersion method loading factors (temperature: 25–50 °C, time: 24–72 h, and SBA‐15 amount: 83.2–252.0 mg) on drug loading percentage (DL%) and dissolution efficiency (DE%). The ABZ loading is confirmed by elemental analysis and Fourier transform infrared spectroscopy. Stability tests are performed, comparing drug dissolution profiles and X‐ray diffraction patterns immediately after loading and after 12 months of storage at 25 °C and 60% relative humidity (RH%). DL% varies between 18% and 36% (w/w), showing that the amount of SBA‐15 is the most significant factor on DL%. The lowest SBA‐15 amount yielded the highest DL%. Regarding DE%, all the design samples exhibit higher values than pure ABZ, with the amount of SBA‐15 being the primary influencing factor. Several samples from the BBD show high DE% (>70%) corresponding to high DL% values. After 12 months, most samples maintain similar dissolution profiles, demonstrating the good stability of the drug in the carrier over time. This study provides valuable insights into optimizing the loading process to enhance ABZ solubility and long‐term stability using mesoporous SBA‐15.

The vehicle of administration, feed or water, and prandial state influence the oral bioavailability of amoxicillin in piglets.

Feed and water components may interact with drugs and affect their dissolution and bioavailability. The impact of the vehicle of administration (feed and water) and the prandial condition of weaner piglets on amoxicillin´s oral bioavailability was evaluated. First, amoxicillin's in vitro dissolution and stability in purified, soft, and hard water, as well as release kinetics from feed in simulated gastric and intestinal media were assessed. Then, pharmacokinetic parameters and bioavailability were determined in fasted and fed pigs using soft water, hard water, or feed as vehicles of administration following a balanced incomplete block design. Amoxicillin showed similar dissolution profiles in soft and hard water, distinct from the dissolution profile obtained with purified water. Complete dissolution was only achieved in purified water, and merely reached 50% in soft or hard water. Once dissolved, antibiotic concentrations decreased by around 20% after 24h in all solutions. Korsmeyer-Peppas model best described amoxicillin release from feed in simulated gastric and intestinal media. Feed considerably reduced antibiotic dissolution in both simulated media. In vivo, amoxicillin exhibited significantly higher bioavailability when delivered via water to fasted than to fed animals, while in-feed administration yielded the lowest values. All treatments showed a similar rate of drug absorption. In conclusion, we demonstrated that water and feed components, as well as feed present in gastrointestinal tract of piglets decrease amoxicillin´s oral bioavailability. Therefore, the use of oral amoxicillin as a broad-spectrum antibiotic to treat systemic infections in pigs should be thoroughly revised.

Model Independent and Dependent Methods for Dissolution Profiles Comparison: Can we take the Road Less Travelled?

Dissolution testing plays an important role in pharmaceutical development due to its ability to provide critical insight into in vivo performance. Dissolution testing during routine pharmaceutical development can ensure batch-to-batch consistency and helps to ensure that the commercial batches are of representative quality to that of studied in the pivotal clinical studies. For comparing the dissolution profiles, there are multitude of approaches suggested by various regulatory agencies that consist of model independent and dependent approaches. The present review aims to summarize the current understanding of dissolution profile similarity approaches. Dissolution profile comparison approaches suggested by various regulatory agencies were compared and contrasted. Further, detailed procedural aspects were provided for the determination of similarity using model independent and dependent approaches. Model independent approaches such as f2 bootstrap, and Multivariate Statistical Distance (MSD) were portrayed from a practical perspective. Advanced tools such as Bias-Corrected and accelerated (BCa) for f2 bootstrap were discussed in depth. Further, model dependent approaches such as zero order, and Weibull models were discussed from realistic scenarios. Finally, the utility of modeling and simulation approaches such as physiologically based pharmacokinetics model (PBPK) and physiologically based biopharmaceutics model (PBBM) were discussed in the context of their ability and potential to supersede traditional dissolution dissimilarity. Overall, this article acts as a ready-to-use guide for pharmaceutics and biopharmaceutics scientists for effective methodologies for dissolution profile comparison for internal decision-making and regulatory justifications.

PREDICTION OF SULFAMETHOXAZOLE AND TRIMETHOPRIM PLASMA LEVELS FROM TABLETS AND DISSOLUTION MEDIA OF PHYSIOLOGICAL RELEVANCE

Objective: To estimate plasma concentrations-time profiles of Sulfamethoxazole (SMZ) and Trimethoprim (TMP) from fixed-dose combination formulations through in vitro data of dissolution media of physiological relevance and a convolution model. Methods: Dissolution profiles of SMZ/TMP tablets (400/80 mg) were obtained with USP paddle apparatus at 100 rpm and 900 ml of 0.1 N HCl, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer. The reference drug product and two generic formulations were tested. Drugs were quantified by a derivative method. Dissolution profiles were compared with model-dependent and independent methods. SMZ/TMP plasma levels were simulated with dissolution data and published in vivo information. Percent of prediction error (PE) for peak plasma concentration (Cmax) and area under the curve from zero time to infinity (AUC0-inf) at each condition were calculated. Results: In all used conditions, similar dissolution profiles were found excepting for TMP at pH 1.2 (f2<50). The in vitro release performance for reference and generic formulations was explained by the Weibull function only for SMZ at pH 6.8 and TMP at pH 4.5. Values of PE>19% for both generic formulations were found with TMP at pH 1.2. Conclusion: Significant differences in TMP dissolution profiles of generic formulations at pH 1.2 reflect the subsequent differences found in predicted Cmax and AUC0-inf.

Dissolution profile evaluation of selected brands of amoxicillin-clavulanate potassium 625 mg tablets retailed in Hawassa town, Sidama Regional State, Ethiopia

Poor quality amoxicillin-clavulanate potassium tablets have been recently discovered in generic drugs related to Augmentin-like medicines containing amoxicillin and clavulanic acid, as well as its derivatives containing falsified active ingredients. One of the most important dosage form characteristics are a detailed active pharmaceutical ingredients dissolution release profile evaluation obtained through dissolution testing. The dissolution test is used in the development of both brand-name and generic drugs. Prior to beginning bioequivalence studies, it is critical to compare the dissolution profiles of various pharmaceutical products. As a result, dissolution is a critical quality control parameter for drugs because it has a direct impact on absorption of pharmaceutical products. Dissolution profile evaluation of seven brands of amoxicillin-clavulanate potassium tablets is retailed in Hawassa town, Sidama Regional State, Ethiopia. The seven brands of amoxicillin-clavulanate potassium tablets were collected from Hawassa town, Sidama Regional State, Ethiopia. The dissolution study was conducted as per USP40-NF35. Then, the dissolution profile test results were compared by one-way ANOVA Dunnett’s test, model independent, and model dependent method. All of the included brand tablets complied with a single-point dissolution study specification. All brand tablets had similar dissolution profiles (p > 0.05), difference factor (f1) < 15%, and dissolution efficiency (≤10%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$(\\le 10\\varvec{\\%}$$\\end{document}). However, the f2 (similarity factor) value justifies that all brand tablets were not within USFDA specification (≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document}50%). The evaluated brands followed the Korsemeyer-Peppas followed by the Weibull curve models. All brand tablets passed the single point USP dissolution specification and the USFDA therapeutic interchangeability guideline. The similarity factor (f2), on the other hand, confirmed that none of the tested brand tablets were interchangeable with the innovator product. Therefore, researchers, national medicine regulatory bodies, and the manufacturer should conduct a properly designed dissolution test as proof of an in vitro bioequivalence study supported by in vivo bioavailability data.

Impact of crystal polymorphism of rifaximin on dissolution behavior

IntroductionRifaximin is an intestinal antiseptic which has five (pseudo) polymorphs α, β, γ, δ and ε. These last (pseudo)polymorphs have different physicochemical properties. The objective of the study is to assess the impact of rifaximin polymorphism on its dissolution rate which could affect its bioavailability. Material and methodsThe analytical validation of dissolution assay method by UV–Visible spectrophotometry was carried out according to ICH Q2. The physicochemical characterization (solubility test, FTIR, DSC, XRD) was carried out on four active pharmaceutical ingredient (MP1, MP2, MP3, MP4). MP1 and MP2 were used by the manufacturer of generic brand 1 (G1) and MP3 and MP4 were used by the manufacturer of generic brand 2 (G2). The comparative in-vitro dissolution study was carried out on the leader brand (P), G1 and G2. ResultsThe four MPs were analyzed by XRD. The results of analysis showed that MP1 and MP4 were a mixture of α form and amorphous form. MP2 had an amorphous form and MP3 had a crystalline form β. The spectra of FTIR showed that the four MP had characteristics bands of rifaximin in the domain 4000-400 cm−1. The differences between the spectra of the four MPs were observed among the amorphous form (MP2), around the region 1800 to 1820 cm−1 which is attributed to the vibration of the CO group. An additional difference observed among the amorphous form (MP2) is around the region 1400 cm−1 which is attributed to the banding OH. The thermograms of MP1, MP2 and MP4 showed endothermic peaks which are probably attributed to the departure of water which indicate that MP1, MP2 and MP4 are pseudopolymoph (hydrate). For the four MPs, probably the melting points are interrupted by the phenomenon of phase transformations (Crystallization) which are reflected by exothermic peaks around 200°C–250 °C.Our results showed that the crystalline polymorphism of rifaximin influences its solubility. According to the results of the solubility test, the β crystal form of rifaximin (MP3) had the lowest solubility (3.47 μg/ml). MP2 had the highest solubility (8.35 μg/ml) and MP1 and MP4 had intermediate solubilities (5.47 μg/ml and 6.74 μg/ml). Comparative in vitro dissolution results showed that the dissolution profile of P was not similar to that of G1 and G2 (% dissolution (P)30min = 60%; % dissolution (G1) 30 min = 100% and % dissolution (G2) 30 min = 115%; f1(P versus G1) = 44; f1(P versus G2) = 61) in M1, while G1 and G2 had comparatively similar dissolution profiles (% dissolution (G1) 30 min = 100%; % dissolution (G1) 30 min = 110%; f1 (G1 versus G2) = 14) in M1. ConclusionThis study highlighted the impact of rifaximin polymorphism on its physico-chemical properties (crystal structure, thermal behavior, solubility) and on its dissolution behavior which could affect the rifaximin bioavailability.

Trace polymer coated clarithromycin spherulites: Formation mechanism, improvement in pharmaceutical properties and development of high-drug-loading direct compression tablets

Clarithromycin (CLA) is a high dose antibiotic drug exhibiting poor flowability and tabletability, making the tablet development challenging. This study aims to develop spherulitic CLA by introducing trace amount of polymer in crystallization solution. Its formation mechanism, physicochemical properties and potential for the direct compression (DC) tablets development were also investigated. Morphological analyses and the in situ observation on crystallization process revealed that the CLA spherulites are formed by fractal branching growth from both sides of the threadlike precursor fibers. 1H NMR analysis and nucleation time monitoring indicated that the existence of hydroxypropyl cellulose in solution slowed down the crystal nucleation and growth rate by forming hydrogen bonding interactions with CLA molecules, making the system maintain high supersaturation, providing high driving forces for CLA spherulitic growth. In comparison to commercial CLA, the CLA spherulites exhibit profoundly improved flowability, tabletability and dissolution behaviors. XPS, contact angle and Raman mapping analysis confirmed the presence of a thin HPC layer on the surfaces and interior of CLA spherulitic particles, resulting in increasing powder plasticity, interparticulate bonding strength and powder wettability, thus better tabletability and dissolution performances. The improved flowability and tabletability of CLA spherulites also enabled the successful development of DC tablet formulation with a high CLA loading (82.8 wt%) and similar dissolution profiles to reference listed drug. This study provides a novel solid form of CLA with superior manufacturability for further development.

Development of Quantitative Comparative Approaches to Support Complex Generic Drug Development.

On October 27-28, 2022, the US Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) hosted a virtual public workshop titled "Best Practices for Utilizing Modeling Approaches to Support Generic Product Development." This report summarizes the presentations and panel discussions for a session titled "Development of Quantitative Comparative Approaches to Support Complex Generic Drug Development." This session featured speakers and panelists from both the generic industry and the FDA who described applications of advanced quantitative approaches for generic drug development and regulatory assessment within three main topics of interest: (1) API sameness assessment for complex generics, (2) particle size distribution assessment, and (3) dissolution profile similarity comparison. The key takeaways were that the analysis of complex data poses significant challenges to the application of conventional statistical bioequivalence methods, and there are various opportunities for using data analytics approaches for developing and applying suitable equivalence assessment method.

Evaluation of Different Methods for Dissolution Profile Similarity Comparison of Montelukast Tablets in Türkiye

Evaluation of Different Methods for Dissolution Profile Similarity Comparison of Montelukast Tablets in Türkiye

The Influence of the coating on the release of Ibuprofen from the Tablet: Comparative Dissolution Study of the different types of coating

Ibuprofen is a non-steroidal anti-inflammatory drug known for its remarkable therapeutic effects. It can be available in different forms among which are coated and sugar-coated tablets.The objective of this study was to compare the dissolution profile between these two forms. The study was conducted with 5 ibuprofen drugs: 3 generics and one reference drug based on coated tablets, and one drug containing the coated tablets.The parameters used to evaluate and compare the dissolution profiles were the similarity (f2) and difference (f1) factors.The results obtained showed similar dissolution profiles for the two types of coating, with a more significant release for the sugar-coated tabletsduring the first 30 minutes.Dissolution studies are important studies to establish equivalence between generic and brand name drugs, and also to predict the release of the AP.

Quality and in vitro bioequivalence evaluation of different brands of amoxicillin + clavulanic acid (500 + 62.5) mg tablets distributed in Burkina Faso

In a previous study, we reported the evaluation of the physicochemical quality and in vitro bioequivalence of different brands of amoxicillin capsules 500 mg marketed in Burkina Faso. As our goal was to document the quality and biopharmaceutical performance of essential antibiotics marketed in resource-limited countries, we investigated here, the interchangeability with the originator of five brands of amoxicillin + clavulanic acid (500mg+62.5mg) tablets distributed in Burkina Faso. The physicochemical quality of the different brands was first verified according to the USP monograph. The comparative evaluation of the in vitro dissolution profiles was performed in three different pH environments (1.2 - 4.5 - 6.8) using statistical calculations of the difference (f1) and similarity (f2) factors. All brands of amoxicillin + clavulanic acid (500mg+62.5mg) tablets, including the originator, met USP specifications for weight uniformity, identification, content and dissolution of active ingredients. However, the similarity and difference factor values showed that two generic brands (B and E) did not have similar amoxicillin dissolution profiles to the comparator product in pH 4.5 media (f1 = 23,54 and 17.02; f2=35.96 and 46.90, respectively). Therefore, these two products cannot be used interchangeably with the originator. The other three generic brands were similar to the originator and can therefore probably be used interchangeably.

Impact of Additives on Drug Particles during Liquid Antisolvent Crystallization and Subsequent Freeze-Drying.

The impact of single or combinations of additives on the generation of nanosuspensions of two poorly water-soluble active pharmaceutical ingredients (APIs), fenofibrate (FF) and dalcetrapib (DCP), and their isolation to the dry state via antisolvent (AS) crystallization followed by freeze-drying was explored in this work. Combinations of polymeric and surfactant additives such as poly(vinyl alcohol) or hydroxypropyl methyl cellulose and sodium docusate were required to stabilize nanoparticles (∼200-300 nm) of both APIs in suspension before isolation to dryness. For both FF and DCP, multiple additives generated the narrowest, most-stable particle size distribution, with the smallest particles in suspension, compared with using a single additive. An industrially recognized freeze-drying process was used for the isolation of these nanoparticles to dryness. When processed by the liquid AS crystallization followed by freeze-drying in the presence of multiple additives, a purer monomorphic powder for FF resulted than when processed in the absence of any additive or in the presence of a single additive. It was noted that all nanoparticles freeze-dried in the presence of additives had a flat, flaky habit resulting in large surface areas. Agglomeration occurred during freeze-drying, resulting in micron-size particles. However, after freeze-drying, powders produced with single or multiple additives showed similar dissolution profiles, irrespective of aging time before drying, thus attenuating the advantage of multiple additives in terms of size observed before the freeze-drying process.

Post-market quality assessment of 22 ciprofloxacin brands by HPLC available in Bangladesh market

Antibiotic resistance has been recognized as a public health threat in recent years, and mortality due to resistance is increasing alarmingly every year. Antibiotic resistance, among many factors, may arise due to the consumption of substandard antibiotic brands that provide subnormal levels of the drug in the blood. Post-market evaluation can provide important information in assessing pharmaceutical products in terms of quality, purity, and therapeutic aspects. Ciprofloxacin, a broad-spectrum antibiotic, has been used against a wide range of infectious diseases in Bangladesh. The present study aimed to determine the quality attributes of twenty-two commonly prescribed brands of ciprofloxacin 500 mg tablet collected from Dhaka city and the rural regions of Jessore. RP-HPLC coupled with UV–visible spectrophotometry was used to determine the potency of ciprofloxacin in tablets, and the zone of inhibition was determined using Kirby-Bauer's disc diffusion method to assess the antimicrobial efficacy against different strains of microorganisms. We found that 95.45% of brands (21 out of 22 brands) of ciprofloxacin tablets met United States Pharmacopoeia (USP) and British Pharmacopoeia (BP) specified potency, whereas one brand failed. From dissolution studies, we observed that 68.2% of brands (15 out of 22 brands) followed USP/NF dissolution test specifications, whereas 31.8% (7 out of 22 brands) failed to release 80% of the labeled amount of drug within 30 min. Drug release kinetics data showed that most brands followed the Weibull drug release kinetic model. Fit factor analysis exhibited that 8 brands out of 22 (36.4%) failed to comply similar dissolution profiles with the reference product. Minimum inhibitory concentrations, assessed against five bacterial strains, further showed good antimicrobial sensitivity by all brands.

Optimization of a Mucoadhesive Vaginal Gel Containing Clotrimazole Using a D-Optimal Experimental Design and Multivariate Analysis.

The aim of this study was to develop a suitable clotrimazole (CLT)-loaded mucoadhesive vaginal gel (CLT-MVG) for topical applications in vaginal candidiasis. Ten CLT-MVG formulations were prepared, consisting of mixtures of acid polyacrylic (Carbopol 940) and polyethene oxides, Sentry Polyox WSRN 1105 or 750, according to an experimental D-optimal design, and CLT was suspended at a ratio of 1%. The prepared CLT-MVG formulations were studied in vitro, and the formulation containing Carbopol 940 0.89% combined with PEO 1105 1.39% was identified with the optimal rheological and in vitro bioadhesion properties, ensuring the prolonged release of CLT, with a similarity factor greater than 50, indicating dissolution profile similarity for three batches of the optimized formulation. This optimized formulation showed a pH in the tolerance range, and an adequate ex vivo mucoadhesion time, while the FT-IR studies revealed no interactions between the excipients and CLT. The microscopic analysis identified a mean particle size of suspended CLT of 5.24 ± 0.57 μm. The in vitro antifungal activity of the optimized formulation was tested on twenty strains of Candida albicans and proved to be better compared to a marketed clotrimazole preparation, showing a greater inhibition effect (p < 0.05). The optimized formulation could be a good candidate for the local treatment of vaginal mycosis.

Dissolution Profile Similarity Assessment—Best Practices, Decision Trees and Global Harmonization

During the write-up of the meeting summary reports from the 2019 dissolution similarity workshop held at the University of Maryland's Center of Excellence in Regulatory Science and Innovation (M-CERSI), several coauthors continued their discussions to develop a "best-practice" document defining the steps required to assess dissolution profiles in support of certain biowaivers and postapproval changes. In previous reports, current challenges related to dissolution profile studies were discussed such that the steps outlined in the two flow charts ("decision trees") presented here can be applied. These decision trees include both recommendations for the use of equivalence procedures between reference and test products as well as application of the dissolution safe space concept. Common approaches towards establishing dissolution safe spaces are described. This paper encourages the preparation of protocols clearly describing why and how testing is performed along with the expected pass/fail criteria prior to generating data on the materials to be evaluated. The target audience of this manuscript includes CMC regulatory scientists, laboratory analysts, as well as statisticians from industry and regulatory health agencies involved in the assessment of product quality via in vitro dissolution testing. Building upon previous publications, this manuscript provides a solution to the current ambiguity related to dissolution profile comparison. The principles outlined in this and previous manuscripts provide a basis for global regulatory alignment in the application of dissolution profile assessment to support manufacturing changes and biowaiver requests.

3D Printing Technology Based on Versatile Gelatin-Carrageenan Gel System for Drug Formulations.

Currently, there is a shortage of pediatric medicines on the market, and 3D printing technology can more flexibly produce personalized medicines to meet individual needs. The study developed a child-friendly composite gel ink (carrageenan-gelatin), created 3D models by computer-aided design technology, then produced personalized medicines using 3D printing to improve the safety and accuracy of medication for pediatric patients. An in-depth understanding of the printability of different formulations was obtained by analyzing the rheological and textural properties of different gel inks and observing the microstructure of different gel inks, which guided the formulation optimization. Through formulation optimization, the printability and thermal stability of gel ink were improved, and F6 formulation (carrageenan: 0.65%; gelatin: 12%) was selected as the 3D printing inks. Additionally, a personalized dose linear model was established with the F6 formulation for the production of 3D printed personalized tablets. Moreover, the dissolution tests showed that the 3D printed tablets were able to dissolve more than 85% within 30 min and had similar dissolution profiles to the commercially available tablets. This study demonstrates that 3D printing is an effective manufacturing technique that allows for flexible, rapid, and automated production of personalized formulations.

Effect of different seed crystals on the supersaturation state of ritonavir tablets prepared by hot-melt extrusion

Hot-melt extrusion (HME) is a technology increasingly common for the commercial production of pharmaceutical amorphous solid dispersions (ASDs), especially for poorly water-soluble active pharmaceutical ingredients (APIs). However, recrystallization of the APIs during dissolution must be prevented to maintain the supersaturation state enabled by ASD. Unfortunately, the amorphous formulation may be contaminated by seed crystals during the HME manufacturing process, which could lead to undesirable crystal growth during the dissolution process. In this study, the dissolution behavior of ritonavir ASD tablets prepared using both Form I and Form II polymorphs was examined, and the effects of different seed crystals on crystal growth rates were investigated. The aim was to understand how the presence of seed crystals can impact the dissolution of ritonavir, and to determine the optimal polymorph and seeding conditions for the production of ASDs. The results showed that both Form I and Form II ritonavir tablets had similar dissolution profiles, which were also similar to the reference listed drug (RLD). However, it was observed that the presence of seed crystals, particularly the metastable Form I seed, led to more precipitation compared to the stable Form II seed in all formulations. The Form I crystals that precipitated from the supersaturated solution were easily dispersed in the solution and could serve as seeds to facilitate crystal growth. On the other hand, Form II crystals tended to grow more slowly and presented as aggregates. The addition of both Form I and Form II seeds could affect their precipitation behaviors, and the amount and form of the seeds had significant effects on the precipitation process of the RLD tablets, as are the tablets prepared with different polymorphs. In conclusion, the study highlights the importance of minimizing the contamination risk of seed crystals during the manufacturing process and selecting the appropriate polymorph for the production of ASDs.

Characterizing interspecies differences in gastric fluid properties to improve understanding of in vivo oral drug formulation performance

An in-depth understanding of the properties of gastric fluid(s) prior to an in vivo pharmacokinetic investigation can vastly improve predictions of in vivo performance. Previously, properties of animal and human gastric fluids have been characterized with varying methods. Unfortunately, characterization has often not been thorough, and some properties, such as density and viscosity, have not been reported. Here, human, porcine and canine gastric fluids were harvested and characterized for pH, viscosity, surface tension, density, and osmolarity. We found that the variability of pH and surface tension between dogs was significantly higher than the variability between pigs, and, furthermore, gastric fluids collected from the same canine species (beagles) housed in two different countries (Denmark and China) had surprisingly different pH values. Next, an in vitro dissolution study in diluted gastric fluids from each species was performed using minitablets containing ibuprofen. Human gastric fluids and porcine gastric fluids showed similar dissolution profiles and corroborated well with biorelevant human Fasted State Simulated Gastric Fluid (FaSSGF). In contrast, differences in canine gastric fluids caused highly variable dissolution results. We systematically compared our findings to those in the literature and based on this evaluation, propose obtaining aspirates from the animals used for in vivo studies to ensure knowledge on the fluid properties affecting the performance of the formulated drug in question.

Development of Gastro-floating drug delivery system by 3D Printing: Impact of formulation and design on the release profile of Baclofen

Objectives: Baclofen is a skeletal muscle relaxant with a short half-life and a narrow absorption window in the upper part of the gastrointestinal tract, and this study aims to formulate a sustained-release tablet of baclofen and 3D printing of gastro-floating device and study the effect of various polymers and device design on the release profile of baclofen.&#x0D; Method: Firstly, four formulas were produced through the hot-melt extrusion and direct compression of the extrudate to produce 30 mg baclofen tablets, then four gastro-floating devices (A, B, C, and D) were designed with two air pockets to enable the floating of the device and have drug-releasing windows with total surface area 4, 10, 20, and 40 mm2 respectively, for drug release. 3D printing of the devices was done by an FDM printer and the tablets were inserted into each device and test it for drug release.&#x0D; Results: Decreasing the surface area of the drug releasing windows revealed a significant reduction in the dissolution of baclofen irrespective of the type of polymers and useful for sustained release formulation but may be associated with lag time. Devices with one and two releasing windows (Device B and C respectively) sometimes revealed similar dissolution profiles and this related to the position of the window regarding the surface of the dissolution media. Device D with four windows and a 40 mm2 surface area was found to produce more reliable results. F3 which contains Eudragit RS-100 as the main polymer showed sustained release in device D where the complete dissolution of the drug occurred in 12 hours, and the gastro-floating device remained floating all the time and was assayed for drug content, FT-IR, and DSC study.&#x0D; Conclusion: Hot-melt extrusion was successfully employed to produce sustained release tablets of baclofen. FDM 3D printers are considered a potential tool to produce gastro-floating devices with the required design and release profile.

Evaluation and Characterization of Stabilized Drug, Formulated as Oro Dispersible Tablet Using Advanced Method

In a challenge to prepare a stable Oro-dispersible tablet (ODT) of Desloratadine, using dry resin was incorporated into a fast-disintegrating matrix to prepare an optimized ODT that achieved the desired criteria of stabilization and patient acceptance. In this study, the critical process parameters (CPPs) and critical material attributes (CMAs) were determined via risk assessment methods within the framework of Quality by Design (QbD). The results showed that resin (Amberlite IRP64®) can be used as a dry stabilizer and the selected variables in the optimization phase have a strong influence on the blend flowability, disintegration time, and wetting time of the ODTs. Furthermore, by comparing the optimized formula with the marketed one, the optimized formula showed a significantly lower disintegration, lower wetting time, and an almost similar dissolution profile.