Drug Dissolution Rate Research Articles

Enhancing the bioavailability of clozapine through microwave-assisted formulation of a stable β-cyclodextrin inclusion complex

The low oral bioavailability of clozapine due to its poor aqueous solubility, poor dissolution rate, and extensive hepatic first-pass metabolism poses a challenge to the effective treatment of psychiatric disorders. The objective of the current research was to address the above issues by developing a clozapine inclusion complex (CLZ-IC) using the microwave irradiation method. To optimize the formulation and processing variables, namely the molar ratio of CLZ to β-CD (X1) and the irritation reaction time (X2), a 32 factorial design was performed. The phase solubility study revealed the formation of a stable inclusion complex with a stoichiometry of 1:1, suggesting that β-cyclodextrin could effectively solubilize clozapine. The characterization data confirmed the formation of the inclusion complex of clozapine in β-cyclodextrin. The optimized inclusion complex showed a solubility of 342 ± 26 µg/ml and a percentage dissolution of 91.1 ± 3.4% after four hours. The inclusion-complex tablets exhibited excellent physical properties and showed an improved in vitro dissolution profile, with 80% of the drug being released within 100 minutes, compared to marketed tablets (80% release in 300 min). In vivo pharmacokinetic studies conducted in a rat model demonstrated an increase in Cmax, area under the curve (AUC), and relative bioavailability by a factor of 2.26 with the optimized formulation, indicating a significant improvement in drug absorption compared to the marketed tablet. The techno-economic analysis suggests a cost-benefit ratio of 25.08 after 7 years, indicating the suitability for large-scale production. Overall, using Design of Experiment, in silico, and in vivo studies proved effective in optimizing the inclusion-complex formation and enhancing the bioavailability of clozapine. In conclusion, the optimized clozapine-β-cyclodextrin inclusion complex prepared using a time-saving (90 sec) and cost-effective microwave irradiation method exhibited excellent physical properties and demonstrated significant improvements in the drug's solubility, dissolution rate, and pharmacokinetic performance.

Quality by Design Based Development of Electrospun Nanofibrous Solid Dispersion Mats for Oral Delivery of Efavirenz

Poor aqueous solubility often results in poor dissolution behavior and, consequently, poor bioavailability for those drugs whose intestinal absorption is dissolution rate limited. It is essential for formulation scientists to identify strategies to improve the solubility and dissolution rate of candidate drugs in order to improve their bioavailability. The present study investigated electrospun polymeric nanofibers for efavirenz (an antiretroviral drug), a Class II drug in the Biopharmaceutical Classification System. In order to fabricate nanofibers, hydrophilic spinnable polymer like Soluplus was used. Statistical design of experiments was used to optimize electrospinning parameters. Scanning electron microscopy (SEM) studies confirmed the presence of nanofibrous material in the mat. The x-ray diffraction (XRD) and differential scanning calorimetry (DSC) studies advocated the amorphization of efavirenz in the nanofiber samples. The optimized nanofiber-based platform significantly improved in vitro dissolution of efavirenz (89.0 ± 3.2% in 120 minutes) compared to pure efavirenz crystals (27.3 ± 2.4%).

Efficiency of single pharmaceutical surfactants to mimic intestinal biorelevant media solubilization and dissolution of etravirine: Comparison of intrinsic and film dissolution models

We understand that quality control dissolution media may best anticipate in vivo product performance by mimicking in vivo media, but preferably involve at most a single pharmaceutical surfactant for routine laboratory use. The objective here was to estimate the concentrations of six pharmaceutical surfactants to mimic etravirine solubility and intrinsic dissolution rate, as well as dissolution rate from a film model, in each Fed State Simulated Intestinal Fluid Version 2 (FeSSIF-V2) and Fasted State Simulated Intestinal Fluid Version 2 (FaSSIF-V2). Solubility studies and colloid sizing measurements were conducted. Results indicate that all six surfactants were more efficient than FeSSIF-V2 or FaSSIF-V2 at solubilizing drug, and also exhibited higher micelle diffusivities than FeSSIF-V2 and FaSSIF-V2 mixed-micelles. The rank-order potency (on mM basis) of the six pharmaceutical surfactants to mimic etravirine solubility in each FeSSIF-V2 and FaSSIF-V2 was: polysorbate 80 (PS80) > polysorbate 20 (PS20) > polyoxyethylene(23) lauryl ether (POE23) > POE10 > hexadecyltrimethylammonium bromide (HEX) > sodium lauryl sulfate (SLS). This rank-order potency was almost the same to mimic drug dissolution rate into each FeSSIF-V2 and FaSSIF-V2, except POE10 > POE23. For the most potent surfactant, PS80, 0.461 mM and 0.140 mM PS80 was estimated to mimic etravirine's solubility and dissolution rate into FeSSIF-V2, respectively, using the intrinsic dissolution model. The low PS80 concentration to mimic dissolution rate reflects the relatively high diffusivity of PS80 micelles, compared to FeSSIF-V2 mixed-micelle diffusivity, which was the case for all six pharmaceutical surfactants. Results are also presented in terms of a film dissolution model for surfactant-mediated dissolution, where dissolution enhancement was less than that in the intrinsic dissolution model, and the film model required lower surfactant concentration than in intrinsic dissolution model to mimic FeSSIF-V2-enhanced dissolution. Findings have promised to identify single pharmaceutical surfactant concentrations that mimic key performance attributes of biorelevant media.

Dosage form Design: From concept to Compliance - Navigating Regulatory Standards and Patient needs

Dosage form design is a pivotal aspect of pharmaceutical formulation, encompassing the meticulous crafting of pharmaceutical products to ensure efficacy, safety, and patient acceptance. This paper comprehensively explores dosage form design, delving into its definition, significance, and multifaceted roles in pharmaceutical development. From therapeutic considerations and biopharmaceutical factors to patient compliance and convenience, every facet of dosage form design is meticulously examined. Therapeutic considerations underscore the need for controlled drug release profiles, optimal bioavailability, precise dosing, and route-dependent administration to maximize therapeutic outcomes and minimize adverse effects. Biopharmaceutical factors, such as drug solubility, permeability, dissolution rate, and absorption site, shape dosage form design strategies to enhance drug performance and bioavailability. Moreover, patient compliance and convenience are pivotal in ensuring adherence to treatment regimens, with considerations ranging from dosage frequency and taste to packaging and patient education. Furthermore, this paper elucidates the intricate interplay between dosage form design and regulatory compliance, emphasizing the importance of adhering to rigorous standards to uphold patient safety and efficacy. By synthesizing theoretical insights with practical applications, this review elucidates the comprehensive approach required for effective dosage form design, encompassing scientific rigor, regulatory adherence, and patient-centric considerations.
 Conclusion
 This paper underscores the paramount importance of dosage form design in pharmaceutical development, serving as a cornerstone for optimizing therapeutic outcomes, ensuring patient adherence, and advancing public health initiatives. Through a nuanced understanding of dosage form design principles and their implementation, pharmaceutical scientists and healthcare professionals can forge a path toward innovative drug delivery solutions that transcend conventional boundaries and empower patients to achieve optimal health outcomes.

Sertaconazole-PLGA nanoparticles for management of ocular keratitis

Ocular fungal infections can pose severe health conditions that may develop into vision impairment and blindness. Sertaconazole (STZ) is a widely used antifungal; however, its low aqueous solubility restricts its topical application for managing ocular keratitis. This investigation aimed to develop polymeric nanoparticles as delivery carriers to improve the ophthalmic availability of STZ for treating fungal keratitis. The impact of STZ solid dispersion incorporation within polymeric nanoparticles for in vitro drug release enhancement was also evaluated. STZ-laden PLGA NPs were formulated via nanoprecipitation technology, using a 24-full factorial layout to optimize the formulation. The formed nanoparticles were assessed for encapsulation efficiency percentage, hydrodynamic size, surface charge, and polydispersity index. The selected formula exhibited a particle size of 305.9 ± 4.36 nm, an entrapment efficiency (EE%) of 98.8 ± 0.008%, a surface charge of 22.57 ± 0.23 mV, and a low polydispersity index, indicating a uniform size distribution. Incorporating STZ in a solid dispersion form with PEG 2000 at a 1:3 w/w drug-to-carrier ratio increased the hydrodynamic size of the PLGA NPs. However, no significant variation in the entrapment efficiency percentage was recorded. The developed STZ-solid dispersion-loaded PLGA NPs have round-shaped structures. DSC and FTIR spectroscopy data indicated drug amorphization with successful loading within the PLGA matrix. Introducing the drug as a solid dispersion within PLGA NPs resulted in enhancing the rate of drug dissolution at initial time intervals, followed by a controlled drug release over 24 h. STZ-PEG2000-laden PLGA NPs enhanced permeability through rabbits’ corneas (Papp), 2.5-fold higher versus STZ-loaded PLGA NPs. The antimycotic activity of the developed formulation was tested against Candida albicans, and a 4-fold reduction in the MIC value was detected upon applying the nanoparticles’ formulation embedding STZ solid dispersion versus that containing the free drug. In conclusion, the formulation of solid dispersions of STZ loaded in PLGA nanoparticles may serve as a starting point for an efficient approach to the ocular delivery of hydrophobic medications and a viable setup for the upcoming research in animal models of fungal keratitis.

Design of Etched- and Functionalized-Halloysite/Meloxicam Hybrids: A Tool for Enhancing Drug Solubility and Dissolution Rate.

The study focuses on the synthesis and characterization of Meloxicam-halloysite nanotube (HNT) composites as a viable approach to enhance the solubility and dissolution rate of meloxicam, a poorly water-soluble drug (BCS class II). Meloxicam is loaded on commercial and modified halloysite (acidic and alkaline etching, or APTES and chitosan functionalization) via a solution method. Several techniques (XRPD, FT-IR, 13C solid-state NMR, SEM, EDS, TEM, DSC, TGA) are applied to characterize both HNTs and meloxicam-HNT systems. In all the investigated drug-clay hybrids, a high meloxicam loading of about 40 wt% is detected. The halloysite modification processes and the drug loading do not alter the structure and morphology of both meloxicam and halloysite nanotubes, which are in intimate contact in the composites. Weak drug-clay and drug-functionalizing agent interactions occur, involving the meloxicam amidic functional group. All the meloxicam-halloysite composites exhibit enhanced dissolution rates, as compared to meloxicam. The meloxicam-halloysite composite, functionalized with chitosan, showed the best performance both in water and in buffer at pH 7.5. The drug is completely released in 4-5 h in water and in less than 1 h in phosphate buffer. Notably, an equilibrium solubility of 13.7 ± 4.2 mg/L in distilled water at 21 °C is detected, and wettability dramatically increases, compared to the raw meloxicam. These promising results can be explained by the chitosan grafting on the outer surface of halloysite nanotubes, which provides increased specific surface area (100 m2/g) disposable for drug adsorption/desorption.

Taste Masking of Dexketoprofen Trometamol Orally Disintegrating Granules by High-Shear Coating with Glyceryl Distearate.

Orally disintegrating granules (ODGs) are a pharmaceutical form commonly used for the administration of NSAIDs because of their easy assumption and fast dispersion. The development of ODGs is not easy for drugs like dexketoprofen trometamol (DXKT), which have a bitter and burning taste. In this work, high-shear coating (HSC) was used as an innovative technique for DKXT taste masking. This study focused on coating DXKT granules using the HSC technique with a low-melting lipid excipient, glyceryl distearate (GDS). The HSC technique allowed for the coating to be developed through the thermal rise resulting from the friction generated by the granules movement inside the equipment, causing the coating excipient to soften. The design of the experiment was used to find the best experimental coating conditions in order to gain effective taste masking by suitably reducing the amount of drug released in the oral cavity. The influence of the granule dimensions was also investigated. Coating effectiveness was evaluated using a simulated saliva dissolution test. It was found that low impeller speed (300 rpm) and a 20% coating excipient were effective in suitably reducing the drug dissolution rate and then in taste masking. The coated granules were characterized for their morphology and solid-state properties by SEM, BET, XRPD, DSC, and NIR analyses. A human taste panel test confirmed the masking of DXKT taste in the selected batch granules.

Interactions of Cyclodextrins and their Hydroxyl Derivatives with Etodolac: Solubility and Dissolution Enhancement.

Poor solubility and dissolution rate of drugs are largely responsible for erratic drug absorption and limited oral bioavailability. Etodolac (ETO) is a non-steroidal anti-inflammatory drug (NSAID) that is classified as BCS class II (dissolution rate-dependent absorption). ETO has high safety and efficacy in pain relief and control of inflammation. ETO is commercially available as (400- 600 mg) tablets; poor solubility and dissolution rate of ETO could result in variable oral absorption and inconsistent analgesic responses. The aim of this study was to improve solubility and dissolution rates of ETO by complexation with cyclodextrins (CDs). Four different CDs namely β-, γ-, HP β-CDs, and HP γ-CDs were prepared using three different methods; solvent evaporation (CO), freeze-drying (FD), and physical mixing (PM). The prepared drug: excipient mixtures were investigated for aqueous solubility, as well as via</i> DSC, XRD, FTIR, SEM, dissolution, and docking. The results revealed a solubility phase diagram of the AL type, indicating a 1:1 complexation of ETO: CD. These results agreed with our molecular docking calculations. DSC, FTIR, XRD, and SEM results confirmed the formation of an inclusion complex. The complexation efficiency, solubility, and dissolution enhancement were in the order of HPγ-CD > γ -CD > HPβ-CD > β-CD. FD method was superior to both CO and PM. Superior dissolution enhancements of ETO were recorded for the FD mixture (up to 90% dissolved in less than 10 min). In conclusion, γ- and hydroxypropyl γ-derivative of cyclodextrins can be considered a promising excipient for enhancement of dissolution rates concerned for ETO.

Design and Characterization of a Melt Electrostatic Precipitator for Advanced Drug Formulations

Electrostatic precipitators (ESP) are especially known for the efficient separation of micron and submicron particles from aerosols. Wet electrostatic precipitators are particularly suitable for highly resistive materials. Using these, particles can be directly transferred into a liquid for further processing or safer handling, which is advantageous for either hazardous or valuable materials. In this work, a wet ESP, which enables the separation of highly resistive particles into a heated liquid, was designed and investigated. To do this, spray-dried drug particles were embedded in a molten sugar alcohol to enhance the drug dissolution rate. After cooling, the solidified product showed advantageous properties such as a high drug dissolution rate and easy handling for further processing. For the design of the wet ESP, different discharge electrode configurations were tested. A wall film served as the collection electrode, which was generated by a specially designed distributer die. A laminar flow regime was achieved with a homogeneous film serving as the collection electrode, which is particularly important for a high separation efficiency. A prototype was designed and constructed in this respect. The particle separation into hot liquids or onto hot surfaces is challenging due to thermal effects in ESPs. The influence of thermophoresis and drag force on the particle transport was investigated, and optimum operation parameters were found for the present ESP. A broad field of applications can be covered with the presented device, where particles are embedded in even hot liquids to form liquid suspensions or, as it is presented here, solid dispersions. The dissolution of the drug-containing solid dispersion was studied in vitro. A remarkably faster drug dissolution was observed from the solid dispersion, as compared to a powder mixture of the drug and xylitol.

Formulation and Evaluation of Biopolymer Incorporated Nanogel of Nabumetone

ABSTRACT: The objective of this research was to improve the solubilization, dissolution rate, and thereby anti-inflammatory activity of the BCS class II drug Nabumetone (NSAID). A solid dispersion (SD) approach with Gelucire 50/13 was used to enhance the solubility. Microwave-induced fusion method was used for the development of SD, as it demonstrated a remarkable increase in the solubility and dissolution rate of pure drugs when compared to traditional solid dispersions. A number of parameters of the SD were evaluated in vitro, including solubility, dissolution, and Fourier Transformed Infrared Spectra obtained (FT-IR). The rate of dissolution was inclined to betterment with the drug: polymer ratio 1:0.5 showing drug release 99.60 ± 29. The objective of the work was to evolve a Nanogel for topical delivery of Nabumetone. The emulsification-diffusion method was used to create nanogel using the polymers Carbopol-940, Gelucire-50/13, and triethanolamine as gelling agents. Chitosan was added to the formulation as a biopolymer. Menthol was employed as a penetration enhancer. Using the spontaneous emulsification-diffusion method, six distinct formulations of Nabumetone-loaded Nanogel were successfully created and evaluated for particle size, zeta potential, thermodynamic stability, and rheology study. Using a cellophane membrane, the gels were examined for diffusion study further, and drug content, viscosity, spreadability, pH, and clarity were accessed. The formulation F4 batch had the best in-vitro drug release profile, with a 96.04% release rate over 270 minutes. Optimized gel F4 underwent a skin irritation study on Wistar rats and passed the test. The topical application of Nabumetone as Nanogel proved to be an effective approach to drug delivery.

Formulation and In Vitro Evaluation of Diacerein Microspheres Using Ethyl-cellulose as Rate Retarding Agent

Diacerein is a newly developed anti-inflammatory drug that is chemically and pharmacologically different from NSAIDs. Diacerein is poorly soluble in water and possesses a slower dissolution rate. The development of Diacerein microspheres improved the aqueous solubility and the drug dissolution rate. Similarly, Diacerein microspheres enabled us to control the drug's release rate and minimize the dosing frequency. The solvent evaporation method prepared diacerein microspheres using ethyl cellulose and hydroxyl propyl cellulose as encapsulation material. In this study, six different formulations were prepared using different proportions of ethyl cellulose, and two formulations encompassing different combinations of ethyl cellulose and hydroxyl propyl cellulose were prepared. Different proportions of gelatin were used as emulsifying agents. The formulated microspheres were evaluated through FTIR, SEM, %age yield, chemical assay, release kinetics, in vitro dissolution studies, and entrapment efficiency. FTIR spectra depicted that there was no drug-to-polymer interaction. SEM confirmed the spherical nature of microspheres, and the drug entrapment efficiency was 89%. Our study demonstrates that microspheres could be a suitable technique to formulate DCN sustained release formulation.

Effect of Croscormellose Sodium in Sustained Release Layer of Valsartan in Bilayer Tablet with Clopidogrel as Immediate Drug Release and Valsartan as Sustained Drug Release

The aim of the study was to design and evaluate bilayer tablets of clopidogrel as immediate release and quick relief and valsartan for sustained release and check the effect of croscarmellose sodium (2%) in Carbopol for sustained release action. Bilayer tablets was prepared using direct compression method. Super disintegrants such as Crospovidone, Croscarmellose sodium were evaluated for immediate release of clopidogrel. Polymers HPMC K4, guar gum, ethyl cellulose and carbopol for controlling release of Valsartan. The compressed bilayer tablets were evaluated for weight variation, thickness, hardness, friability, drug content and in vitro drug release in 0.1N HCl and phosphate buffer pH 6.8. All the pre and post compression parameters were found to be within the acceptable limits. The formulations were optimized based on results of dissolution and formulations CF5 for immediate release &amp; VF11 for sustained release. VF11 was formulated with addition of superdisentigrant and showed better controlled release and dissolution similar to VF8. The release kinetics of Valsartan was subject to curve fitting analysis in order to identify the best fit kinetic model. The regression analysis proves that VF11 follow first order release and drug release by diffusion process based on Fick’s law of diffusion. The data for stability studies infer no considerable change in drug content, dissolution rates and other quality control test were within limits.&#x0D; Keywords: Bilayer tablets, clopidogrel, valsartan, direct compression method.

Preparation of glyburide nanocrystals with improved dissolution properties by dry-ball- and wet-bead- milling: Systematic comparison by experimental design of the performance of the two methods

The effectiveness of dry-ball and wet-bead nano-milling methods in producing nanocrystals of glyburide with increased dissolution rate has been compared. A full factorial design was applied to both methods to systematically evaluate the effect of the most critical factors (milling time, milling speed, ball/bead volume, drug amount) on the responses to be optimized (particle size and dissolution rate). Different experimental conditions were found to obtain the best results: the dry-method required to increase frequency and milling time and reduce ball volume and drug amount, while the wet-method to increase milling rate and drug amount and reduce bead volume and milling time. The results obtained under the respective optimal conditions evidenced a similar performance in nanocrystal production (120 and 180 nm for dry-ball and wet-bead milling, respectively) while a higher % dissolved at 10 min (28 vs 14 %) was found for the wet-method, principally ascribed to the presence, in this case, of the solubilizing polymer P188, added as stabilizer. Differently from the wet-method, the dry-method showed no direct relationship between particle size reduction and drug dissolution rate increase. Solid-state studies evidenced a role of the drug crystallinity loss, caused by the dry-milling, in affecting dissolution rate and proved the stability of the drug under both the milling processes.

Stereolithographic 3D printing: Formulation design based on percolation thresholds

Stereolithograpy (SLA) is an optical photosolidification technology, which can be used to produce 3D printed dosage forms. In the present work, the model drug 4-Aminosalicylic was combined with the photopolymer poly(ethylene glycol) diacrylate (PEGDA), the plasticizer poly(ethylene glycol) (PEG) and the photoinitiator diphenyl(2,4,6- trimethylbenzoyl) phosphine oxide (DPPO) to form a printable resin. The design of a commercial SLA printer was modified to enable printing of different light-curing mixtures in the same tank. This optimisation allowed to evaluate up to 18 different resins by printing in parallel, thus reducing time and costs. Resulting 3D printed drug delivery systems were analysed with respect to mechanical parameters and drug dissolution rate. The principles of percolation theory were applied, for the first time, to provide a mechanistic insight into the impact of varying PEGDA-PEG ratios. It could be demonstrated that a critical point is reached at 18 %v/v of PEGDA, representing the minimum amount needed in the resins to produce solid objects. This critical point was related to the site percolation threshold of PEGDA. Additional critical points were identified related to the percolation thresholds of PEGDA and PEG in the formulation. We conclude that percolation theory is a valuable concept to obtain mechanistic insights into 3D printed systems manufactured by SLA and to define the Design Space of these innovative dosage forms.

Dissolution rates of various brands of proton pump inhibitors in combination with domperidone: an in vitro study

Background: Drug solubility, bioavailability, and dissolution rates are important in establishing in vivo efficacy. Eight brands of domperidone proton pump inhibitor combination drugs were compared to enable physicians to take an informed decision regarding the dissolution rates of various domperidone-PPI combinations available in the Indian market to allow identification and prescription of the drug with better bioavailability. Methods: The in vitro dissolution rate of a combination of domperidone-PPI drugs was measured using the United States Pharmacopeia dissolution paddle apparatus. Each flask of the dissolving testing apparatus contained one tablet and 900 mL of the media, which was dissolved in pure water with 1% Tween® stored at 37.4°C. At regular intervals, aliquots were removed, filtered, and the amount of drug released was measured. The cumulative drug release was calculated using a standard formula. Results: P04 and P07 had the fastest and the slowest onsets of action, respectively. P01 (Omez DSR) and P08 exhibited the longest and the shortest durations of action, respectively. The P05, P06, and P08 formulations had greater particulate matter than the other formulations. Under in vitro conditions, the bioavailability of Omez DSR was nearly two-fold higher than P07 and five-fold higher than P08. Conclusions: Although P04 exhibited the fastest onset of action, Omez DSR had the longest duration of action, superior bioavailability, and ensured the rapid and continuous release of domperidone. Omez DSR demonstrated superior properties compared with other brands.

In vitro and in silico methods to investigate the effect of moderately increasing medium viscosity and density on ibuprofen dissolution rate

Medium viscosity can affect drug dissolution rate, however, it is not usually considered in routine dissolution testing or less complex biorelevant media.The effects of moderately increasing medium viscosity on the in vitro and in silico dissolution of ibuprofen were investigated with two viscosity enhancing agents (VEA) (hydroxypropyl methylcellulose (HPMC) and sucrose), three viscosity levels (range 0.7–5.5 mPa.s), two solubilities and two fluid velocities in the paddle, flow-through and intrinsic dissolution apparatuses. A factorial design analysis highlighted which factors significantly affected key dissolution metrics. Experimental results in the flow-through apparatus (FTA) were compared with in silico dissolution profiles generated by an in-house simulation code (SIMDISSOTM).Increasing viscosity reduced the intrinsic dissolution rate of ibuprofen for both VEAs. The dissolution rate reduction was also observed in the FTA with sucrose, but less so with HPMC, suggesting particle wetting, motion and surface area effects. Particle motion simulations suggested reduced particle lifting times as viscosity increased, indicating an effect of viscosity on particle dispersal. The viscosity- and fluid density-mediated reduction in the dissolution rate observed with sucrose was accurately simulated by SIMDISSOTM, in particular at higher velocities. Velocity had a significant impact on dissolution rates in the paddle apparatus, with a significant viscosity-related reduction in dissolution observed in the low solubility-low velocity scenario.Even small increases in medium viscosity can reduce the dissolution rate of a BCS class II drug, and in silico particle motion and dissolution data can assist interpretation of particulate dissolution behaviour.

Complexes of Ibuprofen Thiazolidin-4-One Derivatives with β-Cyclodextrin: Characterization and In Vivo Release Profile and Biological Evaluation.

Generally, NSAIDs are weakly soluble in water and contain both hydrophilic and hydrophobic groups. One of the most widely used NSAIDs is ibuprofen, which has a poor solubility and high permeability profile. By creating dynamic, non-covalent, water-soluble inclusion complexes, cyclodextrins (CDs) can increase the dissolution rate of low aqueous solubility drugs, operating as a drug delivery vehicle, additionally contributing significantly to the chemical stability of pharmaceuticals and to reducing drug-related irritability. In order to improve the pharmacological and pharmacokinetics profile of ibuprofen, new thiazolidin-4-one derivatives of ibuprofen (4b, 4g, 4k, 4m) were complexed with β-CD, using co-precipitation and freeze-drying. The new β-CD complexes (β-CD-4b, β-CD-4g, β-CD-4k, β-CD-4m) were characterized using scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction and a phase solubility test. Using the AutoDock-VINA algorithm included in YASARA-structure software, we investigated the binding conformation of ibuprofen derivatives to β-CD and measured the binding energies. We also performed an in vivo biological evaluation of the ibuprofen derivatives and corresponding β-CD complexes, using analgesic/anti-inflammatory assays, as well as a release profile. The results support the theory that β-CD complexes (β-CD-4b, β-CD-4g, β-CD-4k, β-CD-4m) have a similar effect to ibuprofen derivatives (4b, 4g, 4k, 4m). Moreover, the β-CD complexes demonstrated a delayed release profile, which provides valuable insights into the drug-delivery area, focused on ibuprofen derivatives.

Solubility enhancement of fexofenadine using self-nano emulsifying drug delivery system for improved biomimetic attributes

Fexofenadine is a poorly water-soluble drug, which limit its bioavailability and ultimately therapeutic efficacy. Liquid self-nano emulsifying drug delivery system (L-SNEDDs) is an approach that can enhance the solubility of fexofenadine by increasing its surface area and reducing the particle size, which increases the rate and extent of drug dissolution. In this investigation, L-SNEDDs of fexofenadine was made up using surfactants and co-surfactant. The SNEDDS formulation was optimized using a pseudo-ternary phase diagram and characterized. The optimized L-SNEDDS incorporated fexofenadine were thermodynamically stable and showed mean droplet size and zeta potential of 155nm and -18mV, respectively unaffected by the media pH. In addition, the viscosity, and refractive index were observed 18.4 and 1.49cps, respectively for optimized L-SNEDDS fortified fexofenadine. The results of Fourier transform infrared spectroscopy revealed an insignificant interaction between the fexofenadine and excipients. A drug loading efficiency of 94.20% resulted with a complete in vitro drug release in 2h, compared with the pure drug, which demonstrate significant improvement in the efficacy. Moreover, these results signify that on further in vivo assessment L-SNEDDS fortified fexofenadine can indicate improvement in pharmacokinetic and clinical outcome. Thus, the investigation revealed that, the L-SNEDDs incorporated fexofenadine was most effective with a mixture of surfactant and co-surfactant with improved solubility intend to relieve pain associated with inflammation with single-dose oral administration.

Feasibility study of the use of a homemade direct powder extrusion printer to manufacture printed tablets with an immediate release of a BCS II molecule

Among the various 3D printing techniques, FDM is the most studied in pharmaceutical research. However, it requires the fabrication of filaments with suitable mechanical properties using HME, which can be laborious and time-consuming. DPE has emerged as a single-step printing technique that can overcome FDM limits as it enables the direct printing of powder blends without the need of filaments. This study demonstrated the manufacturing of cylindrical-shaped printed tablets containing CBD, a BCS II molecule, with an immediate release. Different blends of PEO/E100 and PEO/SOL, each with 10 % of CBD, were printed and tested according to the Eur. Ph. for uncoated tablets. Each printed cylinder met the Eur. Ph. specifications for friability, mass variation and mass uniformity. However, only the E100-based formulations enabled a CBD immediate release, as formulations containing SOL formed a gel once in contact with the dissolution medium, reducing the drug dissolution rate.

Preparation and Characterization of Carvedilol Solid Dispersion by Kneading Method

Solid dispersion using hydrophilic carrier is one of the approaches that has a potential to increase solubility, dissolution rate and consequently the oral bioavailability of poorly-water soluble drugs. In this study, class II drug "Carvedilol" (CVD) was used because of its poor solubility, it serves as a model drug that contributes to irregular dissolution and limited bioavailability. CVD: PVP K30 solid dispersion formulations SD1, SD2 and SD3 were prepared by kneading method at different weight ratios ,1:1; 1:2 and 1:4 respectively and evaluated for drug content, solubility and dissolution rate. Kneading method enhances the stability of drugs and suitable for processing thermolabile substances. The optimum solid dispersion ratio was characterized also for drug-carrier interaction by FTIR spectroscopy, and crystallinity by SEM and PXRD and compared with physical mixture and pure drug powder.&#x0D; The results showed that the solubility of carvedilol increased by increasing the proportion of PVP K30 used in the dispersion of the drug. On the other hand, dissolution study revealed a significant enhancement in the dissolution rate of the drug using solid dispersion compared to pure drug and physical mixture. X-ray diffraction of the solid dispersion suggest that the drug's transformation from crystalline to amorphous form may be responsible for the observed improvement in dissolving rate. The carvedilol solid dispersion improved the solubility and dissolution, which depend on the carrier concentration ratio. The dissolution of drugs increased with an increase in carrier content. The studies of PXRD, SEM, and FTIR revealed the amorphous nature of the drug in solid dispersion. The solid dispersion by kneading approach using PVP K30 as a carrier is a potential method for improving CVD's solubility and dissolution rate.