Enhanced Dissolution Rate Research Articles

Formulation and Optimization of Liquisolid Compact for Enhancing Dissolution Properties of Polyphenol Stilbenoid- Resveratrol

Resveratrol is a class II drug in the Biopharmaceutics Classification System (BCS) with poor water solubility (0.03 mg/ml) and high permeability. Liquisolid system is an innovative technique used for enhancing dissolution rate and bioavailability of poorly soluble drugs. The present study demonstrated that Resveratrol loaded SNEDDS and Liquisolid compacts were successfully developed. Ten SNEDDS formulation were formulated with different ratio oil, surfactant and co-surfactant. Out of ten formulations four were selected based on dilution and self-emulsification time. Out of four formulations F4 formulation showed smaller particle size than compared with other formulations. Characterization was done for particle size, polydispersity index and zeta potential was found to be 22.03nm, 0.281 and -1.20Mv respectively. Morphology was found to in spherical shape with the size range of 10-40 nm. In-vitro studies showed that formulation F4 has better release of 90.09% compared to drug in solution of 39.62%. F4, F5, F6 and F9 formulations were selected and converted into Liquisolid compacts using adsorbents Neuslin and Fuji calin and total eight formulations were formulated and Liquisolid compacts made of formulation F4 of Neuslin was found to be better release of 93.53% compared to formulation F4 of Fuji calin. Hence from our study it showed that Neuslin showed better drug release than Fuji Calin and Neuslin can be used to improve solubility and dissolution of poorly water soluble drugs.
 Keywords: Resveratrol, Self-nanoemulsifying drug delivery systems, Liquisolid compacts, Characterization, Neuslin, Fuji calin.

Development of eplerenone nano sono-crystals using factorial design: enhanced solubility and dissolution rate via anti solvent crystallization technique

Objective The purpose of this work was to improve EP solubility by using a sono-crystalization approach to reduce particle size and hence, increase the dissolution rate. Significance Eplerenone (EP) is an antagonist of the aldosterone receptor and is used for the treatment of hypertension and chronic heart failure. EP was classed as biopharmaceutical classification (BCS) class II because of its poor solubility and high permeability, which retards dissolution rate and drug absorption, and decreases bioavailability. Methods Three-factors and two-level (23) multifactorial design have been employed to study the effect of independent variables which are drug concentration; (X1), stabilizer type (X2), and stabilizer concentration (X3) on responses; saturated solubility of EP in distilled water (Y1), saturated solubility in acidic media pH 1.2 (Y2), particle size (Y3), and polydispersity index, PDI (Y4). Also, they were characterized by Fourier transformed infrared spectroscopy (FTIR), Powder X-ray diffraction (PXRD), Differential scanning calorimetry (DSC), and yield percentage. The optimum formula was further subjected to an in-vitro release study. Results The optimized formulation showed a saturated solubility of EP as 1.29, and 1.86 (mg/ml) in distilled water and acidic media (pH 1.2) respectively. Also, the particle size of 133 nm, and PDI of 0.824 with a small percentage of the difference between the observed and predicted values. Ninety-one percent of EP was released within 10 min., and it was completely released within 45 min. with a significantly higher release rate compared to raw drug. Conclusion This work resulted in a satisfactory enhancement of solubility and dissolution rate which, is suitable for further in-vivo analysis.

Quercetin-Loaded Mesoporous Silica Nanoparticle-Based Lyophilized Tablets for Enhanced Physicochemical Features and Dissolution Rate: Formulation, Optimization, and In Vitro Evaluation.

Mesoporous silica nanoparticles (MSNPs) have been proposed as a potential approach for stabilizing the amorphous state of poorly water-soluble actives. This study aimed to improve the physiochemical characteristics of poorly water-soluble quercetin (QT) through a novel lyophilized formulation. Various parameters, including solvent polarity, QT-carrier mass ratio, and adsorption time, were studied to improve the loading of QT into MSNPs. The optimized loaded MSNPs were formulated into lyophilized tablets through a freeze-drying process using hydrophilic polyvinylpyrrolidone (PVP-K30) as a polymeric stabilizer and water-soluble sucrose as a cryoprotectant. The effect of PVP-K30 and sucrose on the particle size, disintegration time, friability, and time required to release 90% of QT were studied using 32 full factorial design. The optimized formula was characterized using different evaluating techniques; for instance, differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, drug content, moisture content, and saturation solubility. The analysis proved that QT was consistently kept in the nanosize range with a narrow size distribution. The loaded silica nanoparticles and the optimized formulation are in an amorphous state devoid of any chemical interaction with the silica matrix or the lyophilization excipients. The optimized formula also featured low friability (less than 1%), fast disintegration (< 30s), and a pronounced enhancement in saturation solubility and dissolution rate. Briefly, we established that the lyophilized MSNPs-based tablet would be a potential strategy for improving the rate of dissolution and, ultimately, the bioavailability of the poorly water-soluble QT.

Supercritical CO2 versus water as an antisolvent in the crystallization process to enhance dissolution rate of curcumin

Antisolvent crystallization approach using either water (in conventional crystallization process (WAS)), or supercritical CO2 (in supercritical anti-solvent crystallization (SCAS)), was employed in presence of hydroxypropyl methylcellulose (HPMC) to enhance the dissolution of curcumin. The impact of pressure, temperature and depressurization time on the SCAS process was studied using the Box-Behnken design to achieve the highest saturation solubility. A physical mixture of curcumin-HPMC was prepared for comparison purposes. Saturation solubility, scanning electron microscopy, differential scanning calorimetry, X-ray diffraction analysis and Fourier transform infrared spectroscopy were conducted to characterize the solid-state characteristics of the crystallized samples. Dissolution studies helped in ascertaining the effects of the crystallization techniques on the performance of the formulation. Curcumin crystalized by different antisolvent displayed varied shapes, sizes, saturation solubility’s and dissolution properties. In SCAS process, the maximum saturation solubility (2.83 µg/mL) was obtained when the pressure, temperature and depressurization time were 275 bars, 55 °C, and 22 min respectively. The SCAS samples showed the highest dissolution (70%) in 30 min compared to WAS (27%), physical mixture (18%) and unprocessed curcumin (16%). The improved dissolution rate of SCAS sample originates from the development of sponge-like particles with augmented porosity, decreased crystallinity as well as increased solubility of curcumin.

Multivariate Data Analysis and Central Composite Design-Oriented Optimization of Solid Carriers for Formulation of Curcumin-Loaded Solid SNEDDS: Dissolution and Bioavailability Assessment.

The study was initiated with two major purposes: investigating the role of isomalt (GIQ9) as a pharmaceutical carrier for solid self-nanoemulsifying drug delivery systems (S-SNEDDSs) and improving the oral bioavailability of lipophilic curcumin (CUN). GIQ9 has never been explored for solidification of liquid lipid-based nanoparticles such as a liquid isotropic mixture of a SNEDDS containing oil, surfactant and co-surfactant. The suitability of GIQ9 as a carrier was assessed by calculating the loading factor, flow and micromeritic properties. The S-SNEDDSs were prepared by surface adsorption technique. The formulation variables were optimized using central composite design (CCD). The optimized S-SNEDDS was evaluated for differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), microscopy, dissolution and pharmacokinetic studies. The S-SNEDDS showed a particle size, zeta potential and PDI of 97 nm, -26.8 mV and 0.354, respectively. The results of DSC, XRD, FTIR and microscopic studies revealed that the isotropic mixture was adsorbed onto the solid carrier. The L-SNEDDS and S-SNEDDS showed no significant difference in drug release, indicating no change upon solidification. The optimized S-SNEDDS showed 5.1-fold and 61.7-fold enhancement in dissolution rate and oral bioavailability as compared to the naïve curcumin. The overall outcomes of the study indicated the suitability of GIQ9 as a solid carrier for SNEDDSs.

Preparation, Characterization and Evaluation of Prasugrel Hydrochloride Nanosuspensions: Its enhancement of dissolution rate and oral bioavailability

The objective of this study was to investigate nanosuspensions for enhancing the solubility and dissolution rate of Prasugrel HCl (PHCl) so as to reduce the fluctuations in its oral bioavailability. Prasugrel Hydrochloride nanosuspensions were prepared using evaporative precipitation method. After preparation, various nanosuspensions were characterized for particle size, scanning electron microscope (SEM), zeta potential, drug entrapment efficiency (EE), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Solubility and in-vitro release of the drug from nanoparticles are determined. The formulations were characterized using techniques such as powder x-ray diffractometry, scanning electron microscopy, in-vitro dissolution and in-vivo absorption in rats. The dissolution rate and oral absorption of Prasugrel Hydrochloride in the form of nanosuspensions was significantly higher than that of oral suspension and pure drug. All the techniques investigated in this study can be used to enhance dissolution rate and oral absorption of prasugrel hydrochloride and thus can reduce the fluctuations in its oral bioavailability. Nanosuspensions demonstrated to be better and superior technique when compared to other techniques investigated in enhancing oral bioavailability of Prasugrel Hydrochloride. Prasugrel hydrochloride nanosuspension was successfully developed using and the bioavailability is 4 folds increased than its pure drug.

SmartFilm Tablets for Improved Oral Delivery of Poorly Soluble Drugs.

(1) Background: Numerous oral drugs exhibit limited bioavailability due to their poor solubility and poor intestinal permeability. The smartFilm technology is an innovative approach that improves the drug aqueous solubility via incorporating the drug in an amorphous state into a cellulose-based matrix, i.e., paper. smartFilms can be transformed into a free-flowing physical form (i.e., paper granules) that can be compressed into tablets with optimum physico-chemical and pharmaceutical properties. The aim of this study was to investigate if smartFilm tablets are suitable for improved oral delivery of poorly water-soluble drugs. (2) Methods: Curcumin is a poorly soluble drug with low intestinal permeability and was used for the production of curcumin-loaded smartFilms. The curcumin-loaded smartFilms were transferred into smartFilm granules which were then compressed into curcumin-loaded smartFilm tablets. The tablets were characterized regarding their physico-chemical and pharmaceutical properties, and the intestinal permeability of curcumin was determined with the ex vivo porcine intestinal model. The ex vivo intestinal permeability of curcumin from the smartFilm tablets was compared to a physical mixture of curcumin and paper and to a classical and to an innovative commercial product, respectively. (3) Results: The produced curcumin-loaded smartFilm tablets fulfilled the European Pharmacopoeia requirements, incorporated curcumin in amorphous state within the cellulose matrix and exhibited an enhanced dissolution rate. The ex vivo intestinal permeation data were shown to correlate to the in vitro dissolution data. The ex vivo intestinal permeation of curcumin from the smartFilm tablets was about two-fold higher when compared to the physical mixture and the classical commercial product. No differences in the ex vivo bioavailability were found between the smartFilm tablets and the innovative commercial product. (4) Conclusions: smartFilm tablets are a cost-effective and industrially feasible formulation approach for the formulation of poorly water-soluble drugs, i.e., BCS class II and IV drugs.

In vitro profiling of fenofibrate solid dispersion mediated tablet formulation to treat high blood cholesterol

Fenofibrate (FNF), an anti-hyperlipidemic agent, suffers from poor water solubility (0.000707mg/ml) and belongs to class II drug as per BCS, shows a slow dissolution rate. The current investigation aimed to fabricate a fast-dissolving tablet of FNF (not available in the commercial market) using solid dispersion technique employing Vitamin E-D-α-Tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) as molecular biomaterial to enhance dissolution rate and reduce the time required to reach the systemic circulation. Firstly, carrier material was selected based on the release study via preparing solid dispersion using the melting method, and prepared solid dispersion was characterized. Secondly, fast-dissolving tablets from solid dispersion were fabricated using the direct compression tool and characterized for X-ray diffraction (XRD) pattern, friability, hardness, content uniformity, weight variation and in vitro disintegration test. The X-ray diffraction study confirmed the successful formation of solid dispersion using vitamin E TPGS by analyzing the change in physical state. The fabricated solid dispersion exhibited higher drug content than a physical mixture of FNF. An excipient interference study was also performed in methanol and 0.75% w/v sodium lauryl sulphate. It revealed no significant alterations in the absorption peak of FNF as analyzed using UV spectroscopy at 287nm. In addition, water absorption ratio phase solubility and wetting time were also assessed. In -vitro release of FNF from developed tablets was found significantly higher (93.23%±3.11; p<0.001) as compared to prepared compressed tablet of pure FNF (12.21±2.34%). The dissolution rate was also determined, and data were then kept to various kinetic models such as zero-order chemical kinetic, first-order chemical kinetic, Hixon-Crowell and Higuchi chemical kinetic. A complete and sequential in vitro and physicochemical characterization of developed formulation was carried out to set-up improved and effective treatment for high blood cholesterol.

A novel route to enhance the dissolution of apatite: Structural incorporation of hydrogen phosphate

Potential use of hydroxyapatite nanoparticles (HANPs) [Ca10(PO4)6(OH)2] as slow P-release fertilizer (SRF) has recently attracted wider attention. However, commercially available HANP (with Ca/P ratio = 1.667) is the least soluble calcium phosphate and thus limits its full potential as an SRF in agronomic applications. In this research, we sought to enhance the dissolution rate of HANPs by enriching hydrogen phosphate (HPO42−) species in the phosphate (PO43−) structural sites. Seven different types of pure crystalline HANPs were synthesized at a range of Ca/P ratio from 1.46 (at pH 6.0) to 2.10 (at pH 12.0). Complementary results from FTIR and solid-state 31P MAS NMR spectroscopies showed that HPO42− species is most abundant in HANPs crystallized at pH 6.0 and gradually depleted at higher pH products. The rate of depletion of HPO42− species is proportional to the increase in carbonate incorporation into the HANP lattice, which preferentially forms B-type carbonated HANPs. The enhanced dissolution rate of HANPs due to hydrogen phosphate incorporation was tested using a flow-through macro-dialysis system that limits the partial transition of HANPs to other solid phases, which otherwise interfere with dissolution. The results show that the dissolution rate of HANPs increased with decreasing pH of synthesis and was highest in HANPs at pH 6.0. The dissolution rate differed by ten times between HANPs synthesized at pH 7.0 and 10.0. Overall, the atom-efficient synthetic route developed and the ability to tune the dissolution rate of HANPs are significant steps forward in improving the P-release efficiency of a potent SRF and is expected to contribute to efforts toward enhancing agricultural sustainability.

Comparison of solvent evaporation and ultrasonicassisted production methods in the development of nimesulide nanosponges and their characterization

Purpose: To compare solvent evaporation and ultrasonic assisted synthesis in preparation of nimesulide nanosponges using polyvinyl-alcohol and Eudragit L100 as a polymer/copolymer and dichloromethane as a cross linker.Methods: Twelve formulations of nimesulide were prepared, six with each method by varying the ratios of both polymer and co-polymer. The resulting nanosponges were evaluated characterized by preformulation studies, production yield (%), differential scanning calorimeter, x-ray diffraction, Fourier transformation infrared spectroscopy, scanning electron microscopy, entrapment efficiency (%), actual drug content (%) and in-vitro dissolution studies.Results: The results revealed that the formulation with high amounts of co-polymer in both methods showed crystalline structures with enhanced dissolution rates in basic media. Drug entrapment was higher for products prepared by solvent evaporation method (74 %) than that prepared by ultrasonic assisted method (61 %). This correlates with the enhanced dissolution rates for products by solvent evaporation method and increased solubility due to drug-polymer complex formation.Conclusion: Formulations made by solvent evaporation method demonstrate higher production yield and drug entrapment. However, both methods exhibit enhanced dissolution rates in basic medium generally as well as other characteristics that are comparable to nanosponges reported in the literature with regard to their comb like structure.

Quality by design-based optimization of formulation and process parameters for berberine nanosuspension for enhancing its dissolution rate, bioavailability, and cardioprotective activity.

Berberine (BER) possesses dissolution rate limited oral bioavailability. The present study deciphers the formulation of nanosuspension loaded with BER for enhancing its cardioprotective potential. The nanosuspension was prepared by a liquid antisolvent precipitation technique using sodium lauryl sulfate as a surfactant and polyvinyl pyrrolidone K30 (PVP K30) as a polymer. The optimized formulation showed a particle size of 251.32 ± 4.18 nm, zeta potential of -24.10 ± 1.16 mV, and drug loading capacity of 98.22 ± 2.24%. The results showed about 6.01-fold and 3.54-fold enhancement in the dissolution rate and permeability, respectively, upon loading berberine into nanosuspension. About 8.44-fold increase in Cmax , 27.22-fold increase in AUC0-t , and 27.38-fold increase in AUC0-∞ were observed in the case of BER nanosuspension, compared to its naïve form. The results of particle size, zeta potential, and drug loading showed a nonsignificant change in the response of fresh and aged nanosuspension, which indicated that the formulation was stable. In vitro results on H9C2 cell line indicated a lower cellular proliferation rate after treatment with BER nanosuspension with decreased cytoplasmic expression of angiotensin converting enzyme (ACE) protein. Overall, the results indicated the successful development of BER nanosuspension with an enhanced dissolution rate, permeability, bioavailability, and cardioprotective activity. Practical applications The present study provides the evidence that the formulation of nanosuspension loaded with berberine enhance the cardioprotective activity of berberine. The results of the study supports the improved bioavailability of nanosuspension of berberine showed enhanced cardioprotective activity.

Different trends for preparation of budesonide pellets with enhanced dissolution rate

The current research attempts different approaches to overcome the poor dissolution of budesonide (a poorly water-soluble drug) from pellet formulations. Various methods such as liqui-pellet (LP) and pellets made of solid dispersion (SDP) were employed and compared to conventional pellets (CP). In SDP method, budesonide:PVP solid dispersion was prepared followed by extrusion-pelletization. Solid dispersion of budesonide-PVP was also layered to the surface of placebo pellets (LSDP). In LP technique, budesonide dispersed in PEG 400 was mixed with Avicel or Avicel:lactose and was extruded-spheronized. Pellets were evaluated for their shape, size, mechanical properties and dissolution rate. The pellets made by LSDP method were significantly harder than CP or PSDP. LP with a loading factor greater than 0.34 was very soft compared to CP and SDP. Pelletization of budesonide SD (PSDP) did not have a tremendous effect on the dissolution enhancement of budesonide compared to CP whilst LSDP showed faster drug release. In conclusion, the layering of budesonide solid dispersion on placebo pellets (LSDP) was the most promising approach for the production of pellets with the highest dissolution rate so that more than 80% of the drug was released within the first 5 min. Also this formulation had proper mechanical properties. This method has the capability to overcome the poor dissolution of budesonide associated with the pellet containing Avicel, and could be employed for the dissolution enhancement of other poorly water-soluble drugs in pellet form.

Development of sulfamethoxazole-succinimide cocrystal by mechanochemical cocrystallization – An insight into spectroscopic, electronic, chemical conformation and physicochemical properties

Sulfamethoxazole is a sulphonamide bacteriostatic antibiotic having poor solubility, resulting in a high prescribed dose of 800 mg/day. Accordingly, these high doses relate to an increased risk of adverse effects. In this contribution, a novel cocrystal of sulfamethoxazole-succinimide was prepared by mechanochemical synthesis to modulate the physicochemical properties. X-ray diffraction, thermal, and spectroscopic analyses were used to characterize the cocrystal thoroughly. Also, to gain an insight into the optimized structural geometry, important functional frequencies, and electronic properties, the density functional theory was used. The contribution of auxiliary interactions and intermolecular interactions have been investigated by Hirshfeld surface analysis. Solubility and powder dissolution studies were performed to investigate the changes in the physicochemical properties. The cocrystal demonstrated an improvement in the solubility profile in aqueous media and an enhanced dissolution rate in the recommended dissolution media. Furthermore, accelerated stability studies under stress conditions were performed, where the cocrystal showed no indication of dissociation. The study demonstrates the significance of mechanochemical cocrystallization to modulate the physicochemical properties of an API, along with an insight into spectroscopic, electronic and chemical conformation.

Lopinavir-menthol co-crystals for enhanced dissolution rate and intestinal absorption

Lopinavir is an antiretroviral, antiparasitic agent and recently utilized in treatment of COVID-19. Unfortunately, lopinavir exhibited poor oral bioavailability due to poor dissolution, extensive pre-systemic metabolism, and significant P-glycoprotein intestinal efflux. Accordingly, the aim was to enhance dissolution rate and intestinal absorption of lopinavir. This employed co-processing with menthol which is believed to modify crystalline structures and inhibit intestinal efflux. Lopinavir was mixed with menthol at different molar ratios before ethanol assisted kneading. Formulations were evaluated using FTIR spectroscopy, differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and dissolution studies. Optimum ratio was utilized to assess lopinavir intestinal permeability. This employed in situ rabbit intestinal perfusion technique. FTIR, DSC and XRD indicated formation of lopinavir-menthol co-crystals at optimum molar ratio of 1:2. Additional menthol underwent phase separation due to possible self-association. Co-crystallization significantly enhanced lopinavir dissolution rate compared with pure drug to increase the dissolution efficiency from 24.96% in case of unprocessed lopinavir to 91.43% in optimum formulation. Lopinavir showed incomplete absorption from duodenum and jejuno-iliac segments with lower absorptive clearance from jejuno-ileum reflecting P-gp efflux. Co-perfusion with menthol increased lopinavir intestinal permeability. The study introduced menthol as co-crystal co-former for enhanced dissolution and augmented intestinal absorption of lopinavir.

Enhanced solubility and bioavailability of ranolazine by solid dispersion method in vitro and in vivo evaluation

Objective: This study aims to formulate solid dispersions incorporating ranolazine to enhance its aqueous solubility. Methodology: The poor aqueous solubility and permeability of BCS class II drug hamper their bioavailability when orally or topically administered. The present research study focused on formulating amorphous solid dispersions of ranolazine. The hydrophilic polymeric carriers like, HPMC, PEG 6000 and PVPK 30K, Soluplus were used in different ratio. Solid dispersions were prepared by employing modified solvent evaporation method. The prepared physical mixtures and solid dispersions were physico-chemically characterized using fourier transform infrared spectroscopy, scanning electron microscopy, powder x-ray diffractometry, drug content estimation by UV-spectrophotometric method. Result: Functional evaluation of ranolazine solid dispersions was carried out by solubility analysis, in-vitro dissolution studies and pharmacokinetics study. According to solubility studies, Soluplus showed the highest solubility profile among the polymers tested. An optimized ranolazine containing solid dispersions formulation composed of Soluplus at 1:2.5 ratio had 10 fold (41.21 ± 0.35μg/mL) higher solubility and dissolution over that of pure ranolazine (~ 3.92 ± 0.06μg/mL) and physical mixture (~ 4.51 ± 0.32μg/mL). In-vitro dissolution studies revealed that there was increase in solubility of drug and enhanced dissolution rate in solid dispersions compared to physical mixtures respectively.

Fabrication of apigenin nanoparticles using antisolvent crystallization technology: A comparison of supercritical antisolvent, ultrasonic-assisted liquid antisolvent, and high-pressure homogenization technologies

Flavonoids have many positive pharmacological properties, such as antioxidant, antitumor, and anti-inflammatory activities. However, factors such as low water solubility and low dissolution rate limit their use. To overcome their poor solubility, carrier-free apigenin (API) microparticles and nanoparticles were prepared using three types of antisolvent precipitation technologies: supercritical antisolvent (SCF) technology, ultrasonic-assisted liquid antisolvent (UAL) technology, and high-pressure homogenization (HPH) technology. All three technologies can produce uniform tiny particles. However, the API particles obtained using these different techniques show subtle differences in terms of physical and chemical properties and biological activity. The preparation, characterization, and potential use of API microparticles and nanoparticles to improve in vitro release were studied. The resulting API particles were investigated and compared using Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. We determined the optimum conditions for SCF, UAL, and HPH technologies to produce API microparticles and nanoparticles. The antioxidant and antitumor properties of the API particles were also investigated. The results demonstrated that the reduced particle size of the APIs prepared via SCF, UAL, and HPH technologies contributed to the enhanced dissolution rate, which in turn enhanced API bioactivity.

FORMULATION AND EVALUATION OF 2% CRISABOROLE OINTMENT BY COSOLVENCY METHOD

The aim of the present study is to increase the solubility as well as dissolution rate of Crisaborole drug by the preparation of crisaborole ointment 2% by cosolvency method by using hard paraffin wax, propylene glycol and PEG 400 as cosolvents. This approach of delivering drug is mostly suitable for lipophilic drug and poorly or water insoluble drugs. Crisaborole belongs to class IΙ under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility 0.0234 mg/ml. Hence it is necessary to increase the solubility of drug. The crisaborole ointment was prepared by using paraffin wax as base of the ointment, propylene glycol and PEG 400 as aqueous solvent to increase the solubility and dissolution profile. The prepared ointment was evaluated for Physical Analysis, pH measurements, Rheological Properties (Viscosity), Spread ability, Solubility study, Drug content, In-vitro release studies and Stability study of the formulations. The saturated solubility studies and In-vitro dissolution studies as observes that the increase in solubility of drug and enhanced dissolution rate in ointment as compared to pure drug. From the result of saturation solubility studies it was observed that there was an increase in solubility of drug in ointment formulations as compared to pure drug. With increase in the concentration of co-solvents solubility of drug increased and the ointment containing propylene glycol and polyethylene glycol (F5) and (F6) has increased the solubility up to five times. This improves its wettability resulting in a significant increase in solubility.

Preparation, characterization and antimalarial activity of dihydroartemisinin / β-cyclodextrin spray-dried powder

In this study a factorial design was used to optimize process conditions to produce spray-dried powder of dihydroartemisinin (DHA) with β-cyclodextrin (β-CD). Predicted conditions for maximum yield and minimum residual moisture were as follows: inlet temperature; 120 °C, aspirator setting; 100%, feed rate; 25%, and molar ratio of DHA:β-CD; 1:2. The higher percent inclusion yield was obtained in the spray-dried powder with lower molar ratio of DHA:β-CD. DHA existed in amorphous state in the spray-dried powder with 1:2 M ratio of DHA:β-CD whereas it was in crystalline state in the spray-dried powder with 2:1 M ratio of DHA:β-CD. The inclusion complex formation between DHA and β-CD was revealed by FTIR study. The spray-dried powder of DHA with β-CD showed dramatically enhanced dissolution rate with unchanged antimalarial activity. Moreover, it was chemically and physically stable at 30 °C, 75%RH for 3 months after storage.

A 32 Factorial Design Approach for Formulation and Optimization of Azilsartan Medoxomil Nanosuspension for Solubility Enhancement

Abstract: Background: Azilsartan medoxomil (AZL) is an orally active nonpeptide angiotensin II receptor antagonist with less water solubility and oral bioavailability. Objectives: Increase the solubility and dissolving rate of AZL. Materials and Methods: For formulation we used a probe sonication approach to create nanocrystals. The impacts of independent factors such as % polymer concentration (X1) and sonication duration (X2 min) on dependent variables such as particle size (Y1 nm) and % drug release (DR) were optimised using a 32 response surface methodology (Y2). Results: The prepared batches were examined for size, polydispersity index (PDI), zeta potential, solubility study and dissolution study. AZL nanocrystal (PS2 batch) particle size and zeta potential was found to be 168 ± 10 nm, 0.314 ± 0.02 and - 22.72 ± 2.6 mV respectively. The batch (PS2) with the best results was chosen and subjected to additional testing. In vitro dissolution of all 13 batches and pure drug was in ranges of 51.98-81.99% and 11.23 %, respectively. Conclusion: The FTIR analysis indicated that AZL and soluplus have no physical interaction. DSC, XRD, and SEM investigations revealed that the crystalline form of the medication was converted to an amorphous form, resulting in an improve water solubility and dissolution rate. Thus the studies exhibited nanocrystals prepared by probe sonication method showed significant enhancement in solubility and dissolution rate. Key words: Azilsartan medoxomil (AZL), Nanocrystal, Sonication, Solubility, Drug release.

Box-Behnken Design-based formulation optimization and characterization of spray dried rutin loaded nanosuspension: State of the art

Plant secondary metabolites possess excellent antioxidant properties and reported as important source of antioxidants in nutraceuticals. Rutin is one of the plant secondary metabolites having excellent antioxidant property. It is majorly present in tobacco, rue, buckwheat as well as some citrus fruits such as grapes, lime, orange, buckwheat and lemon. As nutraceutical it is useful in treating osteoporosis, oxidative stress, inflammation, cancer and diabetes. However, its therapeutic efficacy is limited due to its lipophilicity that further causes dissolution rate limited oral bioavailability. The present study deciphers the formulation of nanosuspension loaded with rutin using Box-Behnken Design. The nanosuspension was prepared by media milling using sodium lauryl sulphate as surfactant and hydroxypropyl methyl cellulose K4M as polymer. The ratio of surfactant to rutin, ratio of polymer to rutin, milling time and milling speed were varied as per design to control the particle size and zeta potential. The nanosuspension was then spray dried. The optimized formulation showed particle size, zeta potential and drug loading as 121.24 ± 5.22 nm, -32.83 ± 1.34 mV and 97.66 ± 3.33%, respectively. The results of dissolution and permeability studies showed about 7.5 folds enhancement in dissolution rate and 5.44 folds enhancement in permeability of rutin upon loading into nanosuspension as compared to raw rutin. Upon testing the formulation on Caco2 cells for permeability studies, more than 90% cell were found viable, indicating that the formulation was non-toxic and safe for oral use. The results of powder diffraction (PXRD) revealed unchanged crystallinity of formulation before and after milling, indicating no alteration in crystallinity of drug. The formulation was found stable under accelerated condition of 40 °C/75% relative humidity as indicated by non-significant change in results of particle size, zeta potential, and drug loading of fresh and aged nanosuspension. Overall results indicated successful development of spray dried nanosuspension of rutin.