Improved Dissolution Rate Research Articles

Upscaling co-amorphous formulation of naringin-quinacrine dihydrochloride translating from laboratory to pilot scale using spray drying for improved physicochemical and mechanical properties

The current work focuses on improving the poor physicochemical and mechanical properties of naringin (NRN) and quinacrine dihydrochloride (QDH) by formulating a co-amorphous system where the properties of individual drugs complement each other. Additionally, an attempt was made to evaluate the effectiveness of spray-drying in scaling up the stable co-amorphous formulations produced by lab-scale process like rotary evaporation. Analytical processes including PXRD, DSC, SEM, and FT-IR spectroscopy confirmed the amorphization of NRN-QDH and molecular interactions between two. A significant enhancement in the NRN solubility along with 10 &19-folds improvement in dissolution rate was observed in FaSSGF & FaSSIF. The flow properties and compression behaviour of QDH were improved in the resultant co-amorphous formulation as confirmed by the micromeritics and Heckel analysis. These positive results encourage further investigation of the preclinical studies to prove the pharmacokinetic and dynamic benefits of this combination and their successful transfer to clinical applications.

Nano-strategies for advancing oral drug delivery: Porous silicon particles and cyclodextrin encapsulation for enhanced dissolution of poorly soluble drugs

Development of novel active pharmaceutical ingredients (API) for oral use often face challenges due to low bioavailability. Nanoparticle-based drug delivery systems and cyclodextrin (CD) encapsulation offer promising solutions by enhancing API solubility or dissolution rates. Porous silicon nanoparticles have shown potential to encapsulate APIs in their amorphous form within the pores, improving their dissolution rates compared to crystalline counterparts. A novel synthesis approach, circumventing the expensive and tedious synthesis from Si wafer material, has been developed using centrifugal Chemical Vapor Deposition (cCVD). Herein, various cCVD Si particles were evaluated for their ability to enhance the dissolution rate of the model drugs celecoxib (CEL), phenytoin (PHT), griseofulvin (GRI), diclofenac (DCF) and naproxen (NAP). Our findings demonstrate increased dissolution rates of all tested APIs when formulated with cCVD Si particles, compared to free API in pH 7.4 or pH 2.0. Particle characteristics were largely retained after loading, and the solid state of the loaded APIs were evaluated using Differential Scanning Calorimetry (DSC). Dissolution kinetics were influenced by the particle properties, mass loading and API characteristics. Loading of CD-CEL, −GRI and −DCF complexes into the cCVD Si particles showed a potential for further enhanced dissolution rates, representing the first reported investigation of this combination. In conclusion, the cCVD Si particles are promising for improving the dissolution rate of poorly soluble drugs, potentially due to precipitation of amorphous or metastable forms. Further enhancements were observed upon loading CD-drug complexes, thereby offering promising strategies for optimizing drug bioavailability.

Box Behnken model-based Liquisolid Compact Technique for the improvement of solubility and dissolution rate of Azelnidipine

Box Behnken model-based Liquisolid Compact Technique for the improvement of solubility and dissolution rate of Azelnidipine

Preparation and Characterization of Solid Dispersion of Sorafenib Tosylate for Enhancement of Bioavailability.

Solid dispersions have garnered significant attention as an effective strategy for enhancing the solubility and, consequently, the bioavailability of poorly water-soluble drugs. By forming solid dispersions of these drugs with water-soluble carriers, issues related to limited solubility have been mitigated, leading to improved dissolution rates. The core focus of solid dispersion technology revolves around the creation of two-component systems involving the drug and a polymer, where the successful dispersion and stabilization of the drug play pivotal roles in the formulation development process. As a result, this technology is widely acknowledged as a highly valuable approach for enhancing the dissolution properties of poorly water-soluble drugs. In recent years, a substantial body of knowledge has been amassed concerning solid dispersions. Nonetheless, their practical implementation in the commercial sphere remains somewhat limited. In the current investigation, we embarked on the preparation of a solid dispersion of sorafenib tosylate, with the primary objective of achieving the maximum release of the drug within the shortest possible timeframe. Our aim was to develop and optimize the solid dispersions of sorafenib tosylate in a manner that ensures the successful design and formulation of this system.

Design and development of Fujicalin-based axitinib liquisolid compacts for improved dissolution and bioavailability to treat renal cell carcinoma

Poor dissolution of axitinib (AXT) limits its effectiveness through the oral route. The present study investigated, prospective of liquisolid (LS) technology to improve dissolution rate and oral bioavailability of AXT to treat renal cell carcinoma. LS compacts were fabricated with PEG 200, Fujicalin SG, and Aerosil 200 as solvent, carrier, and coat material, respectively. The behavior of LS-systems during tabletting was investigated using Kawakita, Heckel, and Leuenberger analysis. LS compacts were examined for P-XRD, DSC, SEM, and in vitro drug dissolution. For optimization, a 32 full factorial design was utilized. Cell line A498 was utilized for in vitro cytotoxicity study. A bioavailability study was performed using rabbits. DSC and P-XRD analysis confirmed the transition of crystalline AXT to its partial amorphization and molecular dispersion. Consequently, LS6 demonstrated a significantly rapid drug dissolution (Q20; >99 %) than the directly compressed tablets (18.05 %). Additionally, 2.03-fold increase in oral bioavailability, and inhibited dose-dependent cell growth with 1.75-fold increased apoptosis rate. Overall, an LS6 compact consisting of 15 % AXT concentration in PEG 200 and a 20 w/w ratio of Fujicalin SG: Aerosil 200 exhibited improved formulation properties, enhanced dissolution rate, and bioavailability. Thus developed potential product may contribute low-cost production with patient-improved survival expectations.

Enhancing ketoprofen's solubility and anti-inflammatory efficacy with safe methyl-β-cyclodextrin complexation

Improved solubility and anti-inflammatory (AI) properties are imperative for enhancing the effectiveness of poorly water-soluble drugs, particularly non-steroidal anti-inflammatory drugs (NSAIDs). To address these critical issues, our focus is on obtaining NSAID materials in the form of inclusion complexes (IC) with methyl-beta-cyclodextrin (MCD). Ketoprofen (KTP) is selected as the NSAID for this study due to its potency in treating various types of pain, inflammation, and arthritis. Our objective is to tackle the solubility challenge followed by enhancing the AI activity. Confirmation of complexation is achieved through observing changes in the absorbance and fluorescence intensities of KTP upon the addition of MCD, indicating a 1:1 stoichiometric ratio. Phase solubility studies demonstrated improved dissolution rates after the formation of ICs. Further analysis of the optimized IC is conducted using FT-IR, NMR, FE-SEM, and TG/DTA techniques. Notable shifts in chemical shift values and morphological alterations on the surface of the ICs are observed compared to their free form. Most significantly, the IC exhibited superior AI and anti-arthritic (AA) activity compared to KTP alone. These findings highlight the potential of ICs in expanding the application of KTP, particularly in pharmaceuticals, where enhanced stability and efficacy of natural AIs and AAs are paramount.

Fiber Optics Analysis of Floating Hollow Microspheres for a Poorly Water-Soluble Drug

This study investigates the development and evaluation of floating hollow microspheres for the delivery of omeprazole, a poorly water-soluble drug. The research aims to enhance omeprazole's bioavailability by addressing its low solubility and susceptibility to degradation in an acidic gastric environment. Hollow ethyl cellulose microspheres encapsulating omeprazole were prepared using the solvent evaporation technique. The microspheres displayed 91.3% buoyancy and 82.41% drug entrapment efficiency, with sustained drug release in simulated gastric fluid over 12 hours. Characterization techniques such as X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) were used. XRD analysis indicated that the encapsulated drug was in an amorphous state, improving dissolution rates and bioavailability. FTIR confirmed successful drug encapsulation, and SEM revealed the morphology and porous structure of the microspheres. The results highlighting the potential of floating hollow microspheres to enhance the oral bioavailability of poorly water-soluble drugs. Recommendations include refining the formulation process and exploring microfluidic technology for generating uniform microspheres with high drug loading. The study provides valuable insights for the development of advanced drug delivery systems.

Drug Nanocrystals in Oral Absorption: Factors That Influence Pharmacokinetics.

Despite the safety and convenience of oral administration, poorly water-soluble drugs compromise absorption and bioavailability. These drugs can exhibit low dissolution rates, variability between fed and fasted states, difficulty permeating the mucus layer, and P-glycoprotein efflux. Drug nanocrystals offer a promising strategy to address these challenges. This review focuses on the opportunities to develop orally administered nanocrystals based on pharmacokinetic outcomes. The impacts of the drug particle size, morphology, dissolution rate, crystalline state on oral bioavailability are discussed. The potential of the improved dissolution rate to eliminate food effects during absorption is also addressed. This review also explores whether permeation or dissolution drives nanocrystal absorption. Additionally, it addresses the functional roles of stabilizers. Drug nanocrystals may result in prolonged concentrations in the bloodstream in some cases. Therefore, nanocrystals represent a promising strategy to overcome the challenges of poorly water-soluble drugs, thus encouraging further investigation into unclear mechanisms during oral administration.

Optimization of solid dispersion technique and gliclazide to carrier (PVP K30) ratio for solubility enhancement

Background and objective: Poorly water-soluble dugs provide less dissolution rate and bioavailability; hence, it minimizes the pharmacological effect of orally administered medications. Gliclazide is a sulfonylurea antidiabetic medication of the second generation, used to treat type II diabetes mellitus. It belongs to the class II drugs of biopharmaceutic classification system, indicating that it has high permeability and poor aqueous solubility. The aim of this study is to determine an optimum solid dispersion method and drug to carrier ratio to improve the solubility of gliclazide. Methods: Solid dispersions of gliclazide were formulated with polyvinyl pyrrolidone K30 using various drug to carrier ratios (1:1, 1:3, and 1:5) by utilizing kneading and solvent evaporation methods. Solubility and dissolution rate of solid dispersion formulas were compared with pure drug and co-ground mixtures. The formulations were further evaluated in terms of percentage of yield, drug content, FTIR, SEM, DSC, and XRD studies. Results: The highest solubility improvement of gliclazide was obtained at the ratio 1:5 of gliclazide and PVP K30 utilizing solvent evaporation method, solubility increased about 2.54 folds (98.299 ± 5.77 µg/ml) as compared to pure gliclazide (38.739 µg/ml). Meanwhile, the greatest improvement in gliclazide dissolution rate was observed in the same solid dispersion formula that was about 105.76 % after 30 minutes. FTIR demonstrated no unwanted interaction between the drug and carrier. While, SEM, DSC, and XRD showed crystallinity of the drug was minimized and converted to amorphous form in solid dispersion formula. Conclusion: Based on the investigations of this study, it can be concluded that the drug to carrier weight ratios and preparation methods had the influence on the drug solubility and the release rate. The obtained data revealed that the solvent evaporation is the best method of solid dispersion for enhancing gliclazide solubility using PVP K30 with the ratio 1:5 of the drug and carrier.

Development of Orodispersible Tablets with Solid Dispersions of Fenofibrate and Co-Processed Mesoporous Silica for Improved Dissolution.

Poor water solubility is an important challenge in the development of oral patient-friendly solid dosage forms. This study aimed to prepare orodispersible tablets with solid dispersions of a poorly water-soluble drug fenofibrate and a co-processed excipient consisting of mesoporous silica and isomalt. This co-processed excipient, developed in a previous study, exhibited improved flow and compression properties compared to pure silica while maintaining a high specific surface area for drug adsorption. Rotary evaporation was used to formulate solid dispersions with different amounts of fenofibrate, which were evaluated for solid state properties and drug release. The solid dispersion with 30% fenofibrate showed no signs of crystallinity and had a significantly improved dissolution rate, making it the optimal sample for formulation or orodispersible tablets. The aim was to produce tablets with minimal amounts of additional excipients while achieving a drug release profile similar to the uncompressed solid dispersion. The compressed formulations met the requirements for orodispersible tablets in terms of disintegration time, and the drug release from best formulation approximated the profile of uncompressed solid dispersion. Future research should focus on reducing the disintegration time and tablet size to enhance patient acceptability further.

Design of Experiments-Driven Optimization of Spray Drying for Amorphous Clotrimazole Nanosuspension.

This study employed a Quality by Design (QbD) approach to spray dry amorphousclotrimazole nanosuspension (CLT-NS) consisting of Soluplus® and microcrystallinecellulose. Using the Box-Behnken Design, a systematic evaluation was conducted toanalyze the impact of inlet temperature, % aspiration, and feed rate on the criticalquality attributes (CQAs) of the clotrimazole spray-dried nanosuspension (CLT-SDNS). In this study, regression analysis and ANOVA were employed to detect significantfactors and interactions, enabling the development of a predictive model for the spraydrying process. Following optimization, the CLT-SD-NS underwent analysis using Xraypowder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), Dynamic Scanning Calorimetry (DSC), and in vitro dissolution studies. The resultsshowed significant variables, including inlet temperature, feed rate, and aspiration rate,affecting yield, redispersibility index (RDI), and moisture content of the final product. The models created for critical quality attributes (CQAs) showed statistical significanceat a p-value of 0.05. XRPD and DSC confirmed the amorphous state of CLT in theCLT-SD-NS, and FTIR indicated no interactions between CLT and excipients. In vitrodissolution studies showed improved dissolution rates for the CLT-SD-NS (3.12-foldincrease in DI water and 5.88-fold increase at pH 7.2 dissolution media), attributed torapidly redispersing nanosized amorphous CLT particles. The well-designed studyutilizing the Design of Experiments (DoE) methodology.

Raspberry ketone loaded self nanoemulsifying system of cardamom oil: Assessment of phase behavior, dissolution rate and anti-hyperlipidemic activity

Raspberry ketone (RK), a polyphenolic antioxidant, possesses free radical scavenging against oxidative species and has potential of anti-inflammatory, anti-proliferative and anti-aging activities. Major pharmaceutical restriction associated with RK is its poor dissolution characteristic owing to its hydrophobic nature. Present investigation is an attempt to improve dissolution behavior of RK using cardamom oil (CO) based self nanoemulsifying system (SNE) design and preclinical assessed for anti-hyperlipidemic activity. Demarcation of phase boundaries to exactly locate nanoemulsion areas were explored using ternary plots drawn between CO as oil phase, Tween 80/PEG 600 as Smix at 1:1; 1:2; 2:1 and 3:1 ratios. Previously ternary components were selected on the basis of solubility of RK and aqueous dispersibility of CO. Nanoemulsion areas developed under ternary phase region were quantified using trapezoidal method and found in the order 1:1 > 1:2 > 3:1 > 2:1 of Smix. Aqueous dilutibility of SNEs followed the pattern of dilutions lines drawn across the ternary phase and its interference. Optimized SNE produced 97.1 % transmittance with average droplet size 101 nm, zeta potential −2.27 mV and 0.186 mS/cm conductivity. In-vitro RK release was examined in HCl buffer at pH 1.2 and phosphate buffer at pH 6.8 showed a significant difference in the RK dissolved (p < 0.01) compared to RK suspension (control F6). Optimized formulation (F3) at two doses level (RK loading of 80 and 160 mg/kg) vs. RK suspension (160 mg/kg) was pre-clinically administered for four weeks to assess anti-hyperlipidemic activity. Lipid profile markers (levels of VLDL, HDL, LDL, total triglyceride and total cholesterol) were significantly reduced from nanoemulsion formulation as compared to its suspension. SNE formulations were stable with no appreciable loss in quality and performance for six month storage at 30 ± 2 °C; 65 ± 5 % RH conditions. CO based SNE design significantly extended the ternary area for nanoemulsion development as well as RK solubility; which in turn improved dissolution rate of RK and showed anti-hyperlipidemic activity.

Solubility and Dissolution Rate Enhancement of Aceclofenac by Solid Dispersion Employing Kneading and Solvent Evaporation Techniques

Background: Aceclofenac (ACF) is a non-steroidal anti-inflammatory drug with potent anti-inflammatory and analgesic properties. ACF is belongs to BCS class II which has poor solubility in water (practically insoluble) and high permeability that leads to a low dissolution rate and reduced bioavailability. Objective: to enhance the solubility and dissolution rate of ACF using the solid dispersion method (SD) by two common techniques which were solvent evaporation (SE) and kneading (Kn) by using different carriers Mannitol, PVP k30, Soluplus®, and Urea in both techniques at 1:1 and 1:5 wight ratio. Methods: The effects of type of carrier and preparation method on solubility and dissolution rate of SD were studied. Solid dispersions were characterized for their, percentage yield, drug content, drug solubility and in-vitro dissolution rate in comparison with pure drug. Results: The best formula is obtained by the Kn formula (F16) which was formulated by the use of ACF: Soluplus®: with a weight ratio of 1:5 which gave a high percentage yield (99.5%), high drug content (99.8± 0.003%) and the best solubility enhancement which was 361 folds compared to pure ACF and faster dissolution rate which was 80% in 10 minutes compared to 20% for pure drug. Conclusion: the solubility and in-vitro dissolution rate of ACF was efficiently improved when prepared by SD techniques, utilizing both solvent evaporation and kneading methods. Furthermore, the kneading method was superior to solvent evaporation method due to the greater enhancement of solubility and dissolution rate obtained by all carriers and ratios with higher improvement by 1:5 ratio, and can be considered a successful and efficient strategy for solubility and in-vitro dissolution rate improvement of hydrophobic drugs.

Comparison of two self-nanoemulsifying drug delivery systems using different solidification techniques for enhanced solubility and oral bioavailability of poorly water-soluble celecoxib

In this study, we aimed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) and a solid self-nanoemulsifying granule system (S-SNEGS) to enhance the solubility and oral bioavailability of celecoxib. This process involved the preparation of a liquid SNEDDS (L-SNEDDS) and its subsequent solidification into a S-SNEDDS and a S-SNEGS. The L-SNEDDS consisted of celecoxib (drug), Captex® 355 (Captex; oil), Tween® 80 (Tween 80; surfactant) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS; cosurfactant) in a weight ratio of 3.5:25:60:15 to produce the smallest nanoemulsion droplet size. The S-SNEDDS and S-SNEGS were prepared with L-SNEDDS/Ca-silicate/Avicel PH 101 in a weight ratio of 103.5:50:0 using a spray dryer and 103.5:50:100 using a fluid bed granulator, respectively. We compared the two novel developed systems and celecoxib powder based on their solubility, dissolution rate, physicochemical properties, flow properties and oral bioavailability in rats. S-SNEGS showed a significant improvement in solubility and dissolution rate compared to S-SNEDDS and celecoxib powder. Both systems had been converted from crystalline drug to amorphous form. Furthermore, S-SNEGS exhibited a significantly reduced angle of repose, compressibility index and Hausner ratio than S-SNEDDS, suggesting that S-SNEGS was significantly superior in flow properties. Compared to S-SNEDDS and celecoxib powder, S-SNEGS increased the oral bioavailability (AUC value) in rats by 1.3 and 4.5-fold, respectively. Therefore, S-SNEGS wolud be recommended as a solid self-nanoemulsifying system suitable for poorly water-soluble celecoxib.

Eutectic mixtures containing the active pharmaceutical ingredient ezetimibe: Phase diagrams, solid state characterization and dissolution profiles

Cardiovascular disease represents the leading cause of death worldwide, according to the World Health Organization (WHO) report. One of the treatment strategies is the use of the drug ezetimibe (EZT). This drug is a cholesterol absorption inhibitor with low aqueous solubility, which affects its therapeutic efficacy. The purpose of this paper was to obtain eutectic materials of EZT with methylparaben (MPB), salicylic acid (SCA) and nicotinamide (NTM) coformers, and to study their phase diagrams, dissolution properties and hygroscopicity to assess possible enhancements. Phase and Tamman diagrams were constructed using differential scanning calorimetry (DSC) results. The eutectic materials were characterized by powder X-ray diffraction (PXRD) and polarized light optical microscopy (OM). The hygroscopicity of the materials was assessed at different relative humidities (RH) through dynamic vapor sorption (DVS). The dissolution study was conducted with the materials in powder form, with paddle dissolution, rotating at 50 rpm, in 900 mL of aqueous buffer solution at pH 6.8 and 37 °C. The phase diagrams demonstrated that EZT formed eutectic systems with eutectic molar fractions of 0.59, 0.67 and 0.69 for EZT-SCA, EZT-NTM and EZT-MPB, respectively. The three eutectic materials are characterized as microcrystalline conglomerates of their components. In terms of the hygroscopic behavior of EZT at different RHs, eutectic materials demonstrated lower susceptibility to monohydrate formation compared to the anhydrous form. In dissolution studies, EZT-SCA and EZT-MPB solubilized EZT in amounts 22 % higher than the pure drug in 15 min. On the other hand, EZT-NTM eutectic suppressed the dissolution of EZT down to 56 % at the same time. The results indicated the possibility of obtaining materials with enhanced properties using eutectic mixtures, with improved dissolution rates and hygroscopic stability.

Physicochemical Characterization of Hydroxyapatite Hybrids with Meloxicam for Dissolution Rate Improvement.

Organic-inorganic hybrids represent a good solution to improve the solubility and dissolution rates of poorly soluble drugs whose number has been increasing in the last few years. One of the most diffused inorganic matrices is hydroxyapatite (HAP), which is a biocompatible and osteoconductive material. However, the understanding of the hybrids' functioning mechanisms is in many cases limited; thus, thorough physicochemical characterizations are needed. In the present paper, we prepared hybrids of pure and Mg-doped hydroxyapatite with meloxicam, a drug pertaining to the Biopharmaceutical Classification System (BCS) class II, i.e., drugs with low solubility and high permeability. The hybrids' formation was demonstrated by FT-IR, which suggested electrostatic interactions between HAP and drug. The substitution of Mg in the HAP structure mainly produced a structural disorder and a reduction in crystallite sizes. The surface area of HAP increased after Mg doping from 82 to 103 m2g-1 as well as the pore volume, justifying the slightly high drug amount adsorbed by the Mg hybrid. Notwithstanding the low drug loading on the hybrids, the solubility, dissolution profiles and wettability markedly improved with respect to the drug alone, particularly for the Mg doped one, which was probably due to the main distribution of the drug on the HAP surface.

Investigation of Levan-Derived Nanoparticles of Dolutegravir: A Promising Approach for the Delivery of Anti-HIV Drug as Milk Admixture

Nanoparticles composed of Levan and Dolutegravir (DTG) have been successfully synthesized using a spray drying procedure specifically designed for milk/food admixture applications. Levan, obtained from the microorganism Bacillus subtilis, was thoroughly characterized using MALDI-TOF and solid-state NMR technique to confirm its properties. In the present study, this isolated Levan was utilized as a carrier for drug delivery applications. The optimized spray-dried nanoparticles exhibited a smooth surface morphology with particle sizes ranging from 195 to 329 nm. In the in-vitro drug release experiments conducted in water media, the spray-dried nanoparticles showed 100 % release, whereas the unprocessed drug exhibited only 50 % release at the end of 24 h. Notably, the drug release in milk was comparable to that in plain media, indicating the compatibility. The improved dissolution rate observed for the nanoparticles could be attributed to the solid-state conversion (confirmed by XRD analysis) of DTG from its crystalline to amorphous state. The stability of the drug was verified using Fourier Transform Infra-Red Spectroscopy and Thermogravimetry-Differential Scanning Calorimetry analysis. To evaluate the in-vitro cellular toxicity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted, which revealed the CC50 value of 88.88 ± 5.10 µg/mL for unprocessed DTG and 101.08 ± 37.37 µg/mL for DTG nanoparticles. These results indicated that the toxicity of the nanoparticles was comparable to the unprocessed drug. Furthermore, the anti-HIV activity of the nanoparticles in human cell lines was found to be similar to that of the pure drug, emphasizing the therapeutic efficacy of DTG in combating HIV.

Cinnamon oil-based self-emulsifying system for augmented dissolution and hypoglycemic efficacy of gliquidone

The aim was to formulate self-emulsifying drug delivery systems (SEDDS) to hasten dissolution and oral bioavailability of gliquidone (GLQ) as lipophilic oral hypoglycemic. In the developed formulations, cinnamon oil served as the oily phase, while Tween 20 and Transcutol® HP constituted the surfactant/cosurfactant system. A phase diagram was employed to select formulations showing transparent/translucent system after dispersion. These formulations were loaded with GLQ and subjected to in vitro dissolution studies relative to unprocessed GLQ. Optimum systems providing the fastest release were characterized for globule size and morphology. In addition, the in vivo hypoglycemic effect GLQ-loaded SEDDSs was assessed after oral administration to diabetic rats relative to GLQ aqueous dispersion (control). Optimized GLQ-loaded SEDDSs (3 formulations) displayed a significant improvement of dissolution rate as indicated from the amount dissolved after 5 min which recorded 72.83 %, 83.34 % and 92.38 %. Fast dissolution was parallel correlated with globule size values which were 335.4, 211.8 and 175.8 nm for the same formulations, respectively. Ultrafast dispersion and dissolution were revealed further in the in vivo hypoglycemic effect which was shown increasing the area under blood glucose reduction curve by 1.58, 1.61 and 2.11-fold after administration of the same formulation, compared with the control, respectively. Overall, the developed SEDDSs successfully enhanced both the dissolution rate and the bioavailability of GLQ.

Predictive computational models for assessing the impact of co-milling on drug dissolution

Co-milling is an effective technique for improving dissolution rate limited absorption characteristics of poorly water-soluble drugs. However, there is a scarcity of models available to forecast the magnitude of dissolution rate improvement caused by co-milling. Therefore, this study endeavoured to quantitatively predict the increase in dissolution by co-milling based on drug properties. Using a biorelevant dissolution setup, a series of 29 structurally diverse and crystalline drugs were screened in co-milled and physically blended mixtures with Polyvinylpyrrolidone K25. Co-Milling Dissolution Ratios after 15 min (COMDR15 min) and 60 min (COMDR60 min) drug release were predicted by variable selection in the framework of a partial least squares (PLS) regression. The model forecasts the COMDR15 min (R2 = 0.82 and Q2 = 0.77) and COMDR60 min (R2 = 0.87 and Q2 = 0.84) with small differences in root mean square errors of training and test sets by selecting four drug properties. Based on three of these selected variables, applicable multiple linear regression equations were developed with a high predictive power of R2 = 0.83 (COMDR15 min) and R2 = 0.84 (COMDR60 min). The most influential predictor variable was the median drug particle size before milling, followed by the calculated drug logD6.5 value, the calculated molecular descriptor Kappa 3 and the apparent solubility of drugs after 24 h dissolution. The study demonstrates the feasibility of forecasting the dissolution rate improvements of poorly water-solube drugs through co-milling. These models can be applied as computational tools to guide formulation in early stage development.

Posaconazole-glutaric acid cocrystal tablet with improved Dissolution rate

Posaconazole is used to prevent fungal infections in patients having severely weakened immune system and has poor aqueous solubility which impairs its dissolution in upper gastric fluid producing problems in different formulations. These characteristics hinder its therapeutic application by delaying absorption rate and thereby onset of action. In the present study, an attempt was made to prepare posaconazole cocrystals with improved physicochemical properties for better therapeutic activity. Cocrystals were prepared with glutaric acid in 1:1 molar using ethanol by solvent drop grinding technique. The co-crystals formed were characterized by melting point determination, fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and dissolution studies. Posaconazole-glutaric acid co-crystals were further formulated as fast disintegrating tablets. The IR study revealed the shifting of characteristic bands of posaconazole. The PXRD pattern indicated cocrystal crystallinity and a considerable difference in 2θ value of intense peaks. The variation in fusion endotherm, which is in agreement with melting point, was designated by DSC spectra of posaconazole cocrystal. A significant improvement in the dissolution rate was observed in the case of cocrystals based tablets than pure posaconazole tablets.