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Glaucoma, a leading cause of blindness due to elevated intraocular pressure (IOP), is managed with medications like latanoprost (LAT), a prostaglandin analogue, to enhance aqueous outflow. Despite the challenge posed by eye anatomy and tear dynamics, effective ocular bioavailability via topical administration remains elusive. This study aims to optimize self-assembled nanomicelles incorporating LAT, an anti-glaucoma drug, belonging to BCS Class II (low solubility and high permeability) via a two-level, two-factor full factorial design, the nanomicelles were formulated via direct dissolution method and validated using design of expert. The optimized nanomicelles exhibited a spherical morphology, with a size of 69 nm and encapsulation efficiency of 77.5%, demonstrating a sustained LAT release over 12 h. In normotensive rabbits, the nanomicelles elicited a substantial reduction in intraocular pressure (IOP) by up to 40% for a duration of three days, that was significantly longer than the IOP-lowering efficacy of XALATAN eye drops (24 h). These findings indicated that self-assembled nanomicelles hold promise for enhancing the ocular bioavailability and extending the therapeutic duration of LAT, while providing the physical stability. [ABSTRACT FROM AUTHOR]

Severe cutaneous injuries may not heal spontaneously and may necessitate the use of supplementary therapeutic methods. Electrospun nanofibers possess high porosity and specific surface area, which provide the necessary microenvironment for wound healing. Here in, the nanofibers of Soluplus-soy protein isolate (Sol-SPI) containing mupirocin (Mp) were fabricated via electrospinning for wound treatment. The fabricated nanofibers exhibited water absorption capacities of about 300.83 ± 29.72% and water vapor permeability values of about 821.8 ± 49.12 g/m2 day. The Sol/SPI/Mp nanofibers showed an in vitro degradability of 33.73 ± 3.55% after 5 days. The ultimate tensile strength, elastic modulus, and elongation of the Sol/SPI/Mp nanofibers were measured as 3.61 ± 0.29 MPa, 39.15 ± 5.08 MPa, and 59.11 ± 1.94%, respectively. Additionally, 85.90 ± 6.02% of Mp loaded in the nanofibers was released in 5 days in vitro, and by applying the Mp-loaded nanofibers, 93.06 ± 5.40% and 90.40 ± 5.66% of S. aureus and E. coli bacteria were killed, respectively. Human keratinocyte cells (HaCat) demonstrated notable biocompatibility with the prepared nanofibers. Furthermore, compare to other groups, Sol-SPI-Mp nanofibers caused the fastest re-epithelialization and wound healing in a rat model. The findings of this study present a novel nanofiber-based wound dressing that accelerates the healing of severe skin wounds with the risk of infection. [ABSTRACT FROM AUTHOR]

Abstract Glaucoma, a leading cause of blindness due to elevated intraocular pressure (IOP), is managed with medications like latanoprost (LAT), a prostaglandin analogue, to enhance aqueous outflow. Despite the challenge posed by eye anatomy and tear dynamics, effective ocular bioavailability via topical administration remains elusive. This study aims to optimize self-assembled nanomicelles incorporating LAT, an anti-glaucoma drug, belonging to BCS Class II (low solubility and high permeability) via a two-level, two-factor full factorial design, the nanomicelles were formulated via direct dissolution method and validated using design of expert. The optimized nanomicelles exhibited a spherical morphology, with a size of 69 nm and encapsulation efficiency of 77.5%, demonstrating a sustained LAT release over 12 h. In normotensive rabbits, the nanomicelles elicited a substantial reduction in intraocular pressure (IOP) by up to 40% for a duration of three days, that was significantly longer than the IOP-lowering efficacy of XALATAN eye drops (24 h). These findings indicated that self-assembled nanomicelles hold promise for enhancing the ocular bioavailability and extending the therapeutic duration of LAT, while providing the physical stability.

Abstract Severe cutaneous injuries may not heal spontaneously and may necessitate the use of supplementary therapeutic methods. Electrospun nanofibers possess high porosity and specific surface area, which provide the necessary microenvironment for wound healing. Here in, the nanofibers of Soluplus-soy protein isolate (Sol-SPI) containing mupirocin (Mp) were fabricated via electrospinning for wound treatment. The fabricated nanofibers exhibited water absorption capacities of about 300.83 ± 29.72% and water vapor permeability values of about 821.8 ± 49.12 g/m2 day. The Sol/SPI/Mp nanofibers showed an in vitro degradability of 33.73 ± 3.55% after 5 days. The ultimate tensile strength, elastic modulus, and elongation of the Sol/SPI/Mp nanofibers were measured as 3.61 ± 0.29 MPa, 39.15 ± 5.08 MPa, and 59.11 ± 1.94%, respectively. Additionally, 85.90 ± 6.02% of Mp loaded in the nanofibers was released in 5 days in vitro, and by applying the Mp-loaded nanofibers, 93.06 ± 5.40% and 90.40 ± 5.66% of S. aureus and E. coli bacteria were killed, respectively. Human keratinocyte cells (HaCat) demonstrated notable biocompatibility with the prepared nanofibers. Furthermore, compare to other groups, Sol-SPI-Mp nanofibers caused the fastest re-epithelialization and wound healing in a rat model. The findings of this study present a novel nanofiber-based wound dressing that accelerates the healing of severe skin wounds with the risk of infection.

This study aims to highlight the importance of choosing the appropriate co-polymer or co-polymer mixed combinations in order to design value-added nasal dosage forms. Local therapy of upper respiratory tract-related infections, such as nasal rhinosinusitis is of paramount importance, thus advanced local therapeutic options are required. Dexamethasone was encapsulated into three different polymeric micelle formulations: Soluplus or TPGS-only and their mixed combinations. Dynamic light scattering measurements proved that the particles have a micelle size less than 100 nm in monodisperse distribution, with high encapsulation efficiency above 80% and an at least 7-fold water solubility increase. Tobramycin, as an antimicrobial agent, was co-formulated into the in situ gelling systems which were optimized based on gelation time and gelation temperature. The sol–gel transition takes place between 32–35 °C, which is optimally below the temperature of the nasal cavity in a quick manner below 5 min, a suitable strategic criterion against the mucociliary clearance. In vitro drug release and permeability studies confirmed a rapid kinetics in the case of the encapsulated dexamethasone accompanied with a sustained release of tobramycin, as the hydrophilic drug. [ABSTRACT FROM AUTHOR]

The successful development of an amorphous form of a drug demands the use of process conditions and materials that reduce their thermodynamic instability. For the first time, we have prepared amorphous ibrutinib using the quench-cooling method with very high process efficiency. In the presented study, different formulations of amorphous active pharmaceutical ingredient (API) with Soluplus (SOL) in various weight ratios 1:9, 3:7, and 1:1 were prepared. The obtained samples were stored under long-term (25 ± 2 °C/60%RH ± 5% RH, 12 months) and accelerated (40 ± 2 °C/75%RH ± 5% RH, 6 months) storage conditions. The physical stability of amorphous ibrutinib and ibrutinib–Soluplus formulations was analyzed using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction analysis (XRPD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The lack of significant interactions between the ingredients of the formulation was confirmed by FTIR analysis. An increase in moisture content with an increasing SOL weight ratio was observed under accelerated aging and long-term conditions. Additionally, a slight increase in the moisture content of the stored sample compared to that at the initial time was observed. The results revealed the physical strength of the polymeric systems in the presence of high humidity and temperature. The observed high thermal stability allows the use of various technological processes without the risk of thermal degradation. [ABSTRACT FROM AUTHOR]

The aim of this research was to investigate spray-dried mebendazole (MBZ)–loaded Soluplus-based polymeric micelles (MBZ@PMs) for improved solubility and bioabsorption upon oral administration. Following the MBZ@PM preparation, the formed micellar preparation was examined using FTIR, PXRD, DSC, and TEM techniques to determine its physical and chemical properties. Critical micelle concentration determination studies showed that Soluplus® can effectively generate stable polymeric micelles. Particle size analysis demonstrated spherical shape and a particle size of 538.7 ± 2.129 nm. Solubility studies demonstrated approximately eight times higher solubility of MBZ@PMs vis-à-vis MBZ in PBS pH 6.8 (90.16 ± 2.54 µg/mL v/s 11.97 ± 2.99 µg/mL). Stability studies confirmed that the size distribution and polydispersity index of the prepared polymeric micelles showed negligible variations. In vitro release studies revealed low MBZ release from MBZ@PMs (9.70 ± 3.2% in 2 h) at pH 1.2 and sustained (33.3 ± 3.9%) at PBS pH 6.8 in 48 h. In vivo pharmacokinetic studies showed approximately fourfold higher bioavailability (AUC0-ꝏ 153.81 ± 24.20 v/s 38.20 ± 5.55) and 1.5-fold extended half-life of MBZ from MBZ@PMs (2.13 ± 0.53 v/s 1.44 ± 0.36). Therefore, these unprecedented Soluplus®-based polymeric micelles of Mebendazole can be applied as a potential carrier system to improve the therapeutic efficacy of poorly water-soluble compounds. [ABSTRACT FROM AUTHOR]

Background and objective: Self-nanomicellizing solid dispersion SNMSD is a new formulation that combines solid dispersion and nanomicelle strategies; the strategy involves utilizing a suitable carrier that self-assembles into nanomicelles when interacting with gastrointestinal fluids. Canagliflozin, a sodium-glucose cotransporter-2 inhibitor for treating type 2 diabetes, has been linked to poor absorption due to its insolubility in aqueous media. The study aimed to create self-nanomicellizing solid dispersion systems for canagliflozin to overcome its pharmaceutical limitations and improve oral bioavailability.

Background and objective: Self-nanomicellizing solid dispersion SNMSD is a new formulation that combines solid dispersion and nanomicelle strategies; the strategy involves utilizing a suitable carrier that self-assembles into nanomicelles when interacting with gastrointestinal fluids. Canagliflozin, a sodium-glucose cotransporter-2 inhibitor for treating type 2 diabetes, has been linked to poor absorption due to its insolubility in aqueous media. The study aimed to create self-nanomicellizing solid dispersion systems for canagliflozin to overcome its pharmaceutical limitations and improve oral bioavailability. Materials and Methods: Soluplus® was chosen as a nanocarrier to improve canagliflozin solubility after screening several polymers using a phase solubility study. The solvent evaporation method was selected for preparing the solid dispersion. The optimal formula was characterized through ex vivo permeability and in vitro studies. Results: The CFZ-SNMSD formula, with a particle size PS of 60.77±1.00 nm and polydispersity index PDI of 0.06±0.02, has a stable distribution upon dilution to 20-fold with water. The apparent solubility of canagliflozin in the optimized CFZ-SNMSD formula was enhanced by 904.40±4 folds due to amorphization and nanomicellization, as demonstrated by transmission electron microscopy. CFZ-SNMSD formula showed a significant enhancement in dissolution rate compared to the physical mixture and pure drugs. The dissolution efficiency parameter confirms these findings (DE30, CFZ-SNMSD = 77.20% compared to DE30, pure drug = 18.28%). Studies show that canagliflozin's permeability increases exponentially over time due to Soluplus® dispersibility, solubilization, and glycoprotein inhibitory effect, enhancing bioavailability and overcoming GIT membrane barriers. Conclusions: The study indicates that canagliflozin self-nanomicellizing solid dispersion systems are promising methods for improving the oral bioavailability of canagliflozin medication. [ABSTRACT FROM AUTHOR]

Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug‐loaded nanomicelle system comprising albendazole (ABZ) and paclitaxel (PTX), encapsulated in a novel carrier matrix of D‐tocopheryl polyethylene glycol 1000 succinate vitamin E (TPGS), soluplus and folic acid. Our objective was to develop and optimize this nanoparticulate delivery system using solvent evaporation techniques to enhance the therapeutic efficacy against ovarian cancer. The formulation process involved pre‐formulation, formulation, optimization, and comprehensive characterization of the micelles. Optimization was conducted through a 32 factorial design, focusing on the effects of polymer ratios on particle size, zeta potential, polydispersity index (PDI) and entrapment efficiency (%EE). The optimal formulation demonstrated improved dilution stability, as indicated by a critical micelle concentration (CMC) of 0.0015 mg/mL for the TPGS‐folic acid conjugate (TPGS‐FOL). Extensive characterization included differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and Fourier‐transform infrared spectroscopy (FTIR). The release profile exhibited an initial burst followed by sustained release over 90 h. The cytotoxic potential of the formulated micelles was superior to that of the drugs alone, as assessed by MTT assays on SKOV3 ovarian cell lines. Additionally, in vivo studies confirmed the presence of both drugs in plasma and tumour tissues, suggesting effective targeting and penetration. In conclusion, the developed TPGS‐Fol‐based nanomicelles for co‐delivering ABZ and PTX show promising results in overcoming drug resistance, enhancing solubility, sustaining drug release, and improving therapeutic outcomes in ovarian cancer treatment. [ABSTRACT FROM AUTHOR]

The objective of this study was to prepare and conduct a comparative analysis on 5-fluorouracil (5FU) niosomes stabilized with or without Soluplus, utilizing, respectively, passive loading and active loading techniques. Cholesterol was combined with Span 40 and Tween 40 surfactants to prepare several niosomal formulations by either passive or active methods. Encapsulation efficiency (EE%), loading capacity (LC), mean particle sizes, polydispersity indices (PDI), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), pH stability, and in vitro drug release in bio relevant media of pH 1.2, 6.8, and 7.4 were employed to evaluate the formulations. Batches made using the active loading approach (B1-B5) demonstrated higher entrapment efficiency (25–40%) (p ˂ 0.05) than those made using the passive loading method (20%) (with the exception of batch A1). In comparison to niosomes made using the passive loading method, the active loading methodology produced niosomes with a lower PDI (˂ 0.25) and particle size (˂ 70 nm). SEM revealed spherical and discrete vesicles for the Soluplus stabilized niosomes. Both approaches produced niosomes with prominent hydrogen bonding as observed in the FTIR study. The formulations were stable and sustained drug release, but the active loading strategy imparted a more sustained release pattern than the passively loaded one. Soluplus stabilized niosomes demonstrated higher (p ˂ 0.05) drug release (60–70%) in all release media. Based on the production of smaller particle sizes and narrower size distribution, the active loading strategy may be a more effective way to load hydrophilic medicines such as 5FU into niosomes. [ABSTRACT FROM AUTHOR]

Background: The bioavailability of the drug is influenced by the solubility of the drug in the biological fluids. Solubility and dissolution are the rate-limiting steps for the absorption and bioavailability of BCS class II drugs. Materials and Methods: In the current work, Efavirenz (EFV) has been selected as a model drug for the development and assessment of Solid Dispersion (SD) by solvent evaporation and fusion methods using sugar-based carriers like xylitol, Sorbitol, lactulose, and one nonsugar carrier surplus. First, the drug was assessed for solubility in various solvents. EFV Solid Dispersions (S.D.s) have been produced by solvent evaporation and fusion at different carrier ratios (1:0.5, 1:1, 1:1.5, 1:2, and 1:3). The prepared SDs were subjected to drug content uniformity, saturation solubility studies, and in vitro dissolution studies. Results: Preformulation investigations, such as FT-IR, proved that the excipient and drug molecules are binding with intermolecular hydrogen bonds. EFV was found to be more soluble in 7.4 pH phosphate buffer than in the other solvents. The saturation solubility of EFV was affected by carrier concentration and %yield, and in vitro drug dissolution studies were performed on the S.D.s. Pure EFV released 54.78% of the drug, whereas SDs by solvent evaporation method released 85.28± 1.84%-100.74±1.69% drug, and SDs prepared by fusion method released 76.65±0.98%-99.28±1.95% of the drug in 60 min. Conclusion: SDs of EFV prepared by solvent evaporation and fusion methods have improved the aqueous solubility of EFV, and, in turn, improved the in vitro drug release, and formulation with 1:1.5 drug-to-carrier ratio has been selected as an optimized formulation. [ABSTRACT FROM AUTHOR]

Determining solubility of drugs is laborious and time-consuming process that may not yield meaningful results. Amorphous solid dispersion (ASD) is a widely used solubility enhancement technique. Predictive models could streamline this process and accelerate the development of oral drugs with improved aqueous solubilities. This study aimed to develop a predictive model to estimate the solubility of a compound from the ASDs in polymer matrices. ASDs of model drugs (acetazolamide, chlorothiazide, furosemide, hydrochlorothiazide, sulfamethoxazole) with model polymers (PVP, PVPVA, HPMC E5, Soluplus) and a surfactant (TPGS) were prepared using hotmelt process. The prepared ASDs were characterized using DSC, FTIR, and XRD. The aqueous solubility of the model drugs was determined using shake-flask method. Multiple linear regression was used to develop a predictive model to determine aqueous solubility using the molecular descriptors of the drug and polymer as predictor variables. The model was validated using Leave-One-Out Cross-Validation. The ASDs' drug components were identified as amorphous via DSC and XRD Studies. There were no significant chemical interactions between the model drugs and the polymers based on FTIR studies. The ASDs showed a significant (p < 0.05) improvement in solubility, ranging from a 3-fold to 118-fold, compared with the pure drug. The developed empirical model predicted the solubility of the model drugs from the ASDs containing model polymer matrices with an accuracy greater than 80%. The developed empirical model demonstrated robustness and predicted the aqueous solubility of model drugs from the ASDs of model polymer matrices with an accuracy greater than 80%. [ABSTRACT FROM AUTHOR]

This study aims to highlight the importance of choosing the appropriate co-polymer or co-polymer mixed combinations in order to design value-added nasal dosage forms. Local therapy of upper respiratory tract-related infections, such as nasal rhinosinusitis is of paramount importance, thus advanced local therapeutic options are required. Dexamethasone was encapsulated into three different polymeric micelle formulations: Soluplus or TPGS-only and their mixed combinations. Dynamic light scattering measurements proved that the particles have a micelle size less than 100 nm in monodisperse distribution, with high encapsulation efficiency above 80% and an at least 7-fold water solubility increase. Tobramycin, as an antimicrobial agent, was co-formulated into the in situ gelling systems which were optimized based on gelation time and gelation temperature. The sol–gel transition takes place between 32–35 °C, which is optimally below the temperature of the nasal cavity in a quick manner below 5 min, a suitable strategic criterion against the mucociliary clearance. In vitro drug release and permeability studies confirmed a rapid kinetics in the case of the encapsulated dexamethasone accompanied with a sustained release of tobramycin, as the hydrophilic drug.

Dronedarone (DRN), an antiarrhythmic drug, exhibits potent pharmacological effects in the management of cardiac arrhythmias. Despite its therapeutic potential, DRN faces formulation challenges due to its low aqueous solubility. Hence, the present study is dedicated to the examination of amorphous solid dispersions (ASDs) as a strategic approach for enhancing the solubility of DRN. Initially, the glass forming ability (GFA) of API was assessed alongside its thermal degradation profile, and it was revealed that DRN is a stable glass former (GFA III compound) that remains thermally stable up to approximately 200 °C. Subsequently, five commonly used ASD matrix/carriers, i.e., hydroxypropyl methylcellulose (HPMC), povidone (PVP), copovidone (PVP/VA), Soluplus® (SOL), and Eudragit® E PO (EPO), were screened for the formation of a DRN-based ASD using film casting and solvent shift methods, along with miscibility evaluation measurements. SOL proved to be the most promising matrix/carrier among the others, and, hence, was used to prepare DRN ASDs via the melt-quench method. The physicochemical characterization of the prepared systems (via pXRD) revealed the complete amorphization of the API within the matrix/carrier, while the system was physically stable for at least three months after its preparation. In vitro release studies for the ASDs, conducted under non-sink conditions, revealed the sustained supersaturation of the drug for at least 8 h. Finally, the use of attenuated total reflectance (ATR) FTIR spectroscopy showed the formation of a strong molecular interaction between the drug molecules and SOL. [ABSTRACT FROM AUTHOR]

The research was undertaken to design, develop and characterize the smart lipid system of an inadequate bioavailable Atovaquone (ATQ). The poor aqueous solubility and dissolution are the major constrain of inadequate bioavailability. The solubility study reveals that Labrasol-ALF (L-ALF), Tween 80, and Trancutol®P (TP) were screened as oil, surfactant, and co-surfactant, respectively. The pseudo ternary diagram was constructed to locate the appropriate amount of each ingredient, and a 1:3:1 ratio of l-ALF: Tween 80: TP was chosen. The effect of precipitation inhibitor was assessed using the parachute effect. Soluplus® (SP) was chosen as a precipitation inhibitor at 5%. Ishikawa diagram and qualitative risk assessment were performed to screen the critical material attributes (CMAs) and critical process parameters (CPPs). d-optimal mixture design was explored for the optimization of the formulation. The amount of oil, surfactant, and co-surfactant was screened as independent variables, whereas globule size, poly-dispersibility index (PDI), and solubility were designated dependent variables. The design batches were evaluated for the in-vitro dissolution rate, PDI, zeta potential, globule size, etc. The optimal region was located using an overlay plot. The optimized formulation has shown a 97.91% drug release within 1 h. The value of zeta potential (-27.43 mV) and PDI (0.468) indicates the stability of the formulation. The parachute effect had explored for the selection of precipitation inhibitors. SP was able to increase the solubility of ATQ and reduce the precipitation of the drug. The amount of l-ALF, Tween, 80and TP was significant for the formulation of SNEDDS. The formulation was novel, effective, patient-friendly, and industry oriented.

Evolving therapeutic landscape through combinatorial chemistry and high throughput screening have resulted in an increased number of poorly soluble drugs. Drug delivery strategies quickly adapted to convert these drugs into successful therapies. Amorphous solid dispersion (ASD) technology is widely employed as a drug delivery strategy by pharmaceutical industries to overcome the challenges associated with these poorly soluble drugs. The development of ASD formulation requires an understanding of polymers and manufacturing techniques. A review of US FDA-approved ASD-based products revealed that only a limited number of polymers and manufacturing technologies are employed by pharmaceutical industries. This review provides a comprehensive guide for the selection and overview of polymers and manufacturing technologies adopted by pharmaceutical industries for ASD formulation. The various employed polymers with their underlying mechanisms for solution-state and solid-state stability are discussed. ASD manufacturing techniques, primarily implemented by pharmaceutical industries for commercialization, are presented in Quality by Design (QbD) format. An overview of novel excipients and progress in manufacturing technologies are also discussed. This review provides insights to the researchers on the industrially accepted polymers and manufacturing technology for ASD formulation that has translated these challenging drugs into successful therapies. [ABSTRACT FROM AUTHOR]

Microneedles have recently emerged as a promising platform for delivering therapeutic agents by disrupting the skin, resulting in improved and high drug delivery via this route. Ibuprofen is widely used topically and orally for chronic pain conditions; to avoid untoward gastric effects, topical application is preferred over the oral route. This study aimed to enhance the solubility of the poorly water-soluble ibuprofen using Soluplus (SP) as a solubilizer and to fabricate dissolving microneedle patches of the drug. The fabricated patches were compared with marketed oral and topical formulations of ibuprofen. A 432-fold increase was observed in the solubility of the drug at 8% SP. The FTIR studies revealed that the drug and polymers were compatible. MNs were of uniform morphology and released the drug in a predictable manner. The in vivo analysis on healthy human volunteers revealed a Cmax of 28.7 µg/mL ± 0.5 with a Tmax of 24 h and a MRT of 19.5 h, which was significantly higher than that observed for commercially available topical formulations. The prepared ibuprofen microneedles have higher bioavailability and MRT at a lower dose (165 µg) as compared to tablet and cream doses (200 mg). [ABSTRACT FROM AUTHOR]

BCS class II drugs exhibit low aqueous solubility and high permeability. Such drugs often have an incomplete or erratic absorption profile. This study aimed to predict the effects of β-cyclodextrin (βCD) and different hydrophilic polymers (poloxamer 188 (PXM-188), polyvinyl pyrrolidone (PVP) and soluplus (SOLO)) on the saturated solubility and dissolution profile of hydrophobic model drug rivaroxaban (RIV). Binary inclusion complex with βCD were prepared by kneading and solvent evaporation method, at drug to cyclodextrin weight molar ratios of 1:1, 1:2, and 1:4. Saturated solubility of the hydrophobic model moiety was evaluated with βCD to explore the increment in saturated solubility. Dissolution test was carried out to assess the drug release from the produced binary inclusion complex in the aqueous medium. Solid state analysis was performed using Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) techniques. When compared to pure drug, the binary complex (Drug: βCD at molar ratio of 1:2 w/w) demonstrated the best performance in terms of enhanced solubility and drug release. Furthermore, ternary inclusion complex was prepared with hydrophilic polymers SOLO, PVP K-30 and PXM-188 at 0.5%,1%,2.5%,5% and 10% w/w to optimized binary formulation RIV:βCD (1:2) prepared by kneading (KN) and solvent evaporation (S.E) method. The findings demonstrated that among ternary formulations (1:2 Drug: βCD: SOLO 10% S.E) manifested greatest improvement in saturated solubility and dissolution rate. Results of solubility enhancement and improvement in dissolution profile of model drug by ternary inclusion complexation were also supported by FTIR, DSC, XRD, and SEM analysis. So, it can be concluded that the ternary inclusion systems were more effective compared to the binary combinations in improving solubility as well as dissolution of hydrophobic model drug rivaroxaban.

[Display omitted] This research focuses on exploring the solid solubility and miscibility of Etoricoxib, a poorly water-soluble anti-inflammatory drug, within Soluplus®, a polymer used as a matrix for 3D-printed tablets. By utilizing hot-melt extrusion (HME), the drug was dispersed within Soluplus® to enhance its solubility. The extrudates were then employed in 3D printing to create customized solid oral dosage form. This study's novelty lies in combining HME and 3D printing, aiming to improve drug incorporation, stability, and effectiveness in the final formulation. Comprehensive characterization techniques, including hot stage microscopy (HSM), scanning electron microscopy (SEM), micro-computed tomography (Micro-CT), florescence microscopy, optical microscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), solubility studies, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and aqueous solubility study were utilized to elucidate the physicochemical properties, thermal stability, and structural integrity for the extruded filaments (the printing ink), and 3D printed tablets made thereof. Furthermore, the in vitro drug release profile of the 3D printed tablet was systematically evaluated, revealing a controlled drug release pattern from the finished dosage form. The systematic investigation reported herein, starting from theoretical miscibility to the printing ink development through HME, detailed characterization of the extruded filaments, and further solid oral formulation development by additive manufacturing can be utilized as a platform technology or a pathway for the development of personalized medicine with drugs having similar physicochemical properties. [ABSTRACT FROM AUTHOR]

[Display omitted] Over the last 15 years, a small number of paediatric artemisinin-based combination therapy products have been marketed. These included Riamet® and Coartem® dispersible tablets, a combination of artemether and lumefantrine, co-developed by the Medicines for Malaria Venture and Novartis. Disappointingly, patient compliance, requirement for high-fat meal, and sporadic drug dissolution behaviours following administration still result in considerable challenges for these products. The first and foremost barrier that needs addressed for successful delivery of the artemether/lumefantrine combination is the poor solubility of lumefantrine within the gastrointestinal fluids. In this work, amorphous solid dispersions of lumefantrine within Soluplus®-based matrices have been manufactured using hot melt extrusion as a potential formulation strategy to achieve enhanced dissolution and apparent solubility. The drug loading capacity of Soluplus® to accommodate amorphous lumefantrine, whilst ensuring improved in-vitro dissolution performance, was investigated. The extrusion process employed a variety of processing parameters, including various temperature profiles and different production scales. The influence of variation in extrusion conditions upon the physical stability of manufactured amorphous solid dispersions was also examined. This allowed for a greater understanding of the role of extrusion processing conditions on the performance of supersaturated amorphous solid dispersions during dissolution and storage. This may allow for the design and manufacture of drug enabled formulations with lower drug dosing and thus a lower risk of adverse effects. [ABSTRACT FROM AUTHOR]

Soluplus is a polymer that has been explored to prepare nanocomposites for pulmonary drug delivery and is non-toxic. However, its aerosolization attributes when spray-dried have not been investigated. Hence, this work aimed to investigate the aerosol performance of soluplus-based spray-dried powders. In addition, the potential use of leucine to improve the aerosolization of such particles was also investigated by including leucine at 10 or 20% w/w. 4% w/w salbutamol was used as a model drug in all the formulations primarily to aid quantification during aerosolization evaluation and for assessing the interaction between the drug and soluplus using infrared spectroscopy with the multivariate analysis approach of principal component analysis (PCA). Three formulations (4% salbutamol/96% soluplus, 4% salbutamol/86% soluplus/10% leucine, 4% salbutamol/76% soluplus/20% leucine) were prepared. The formulations were characterized in terms of solid-state, water content, particle size/morphology, and aerosolization. Similarly, two additional formulations (14% salbutamol/86% soluplus and 24% salbutamol/76% soluplus) were prepared to assess potential non-covalent interactions between salbutamol and soluplus. The formulations with only salbutamol and soluplus were amorphous, as evident from X-ray diffraction. Leucine was crystalline in the formulations. All the spray-dried formulations were irregular spheres with surface corrugation. The 96% soluplus powder showed an emitted fraction (EF) and fine particles fraction (FPF) of 91.9 and 49.8%, respectively. The inclusion of leucine at 10% did not increase the EF; however, an increase in FPF (69.7%) was achieved with 20% leucine. PCA of the infrared spectra suggested potential non-covalent interactions between salbutamol and soluplus. It hinted at the potential involvement of ketone groups of the excipient. This study concludes that soluplus-based spray-dried powder with or without leucine can potentially be utilized for pulmonary drug delivery. In addition, PCA can effectively be utilized in assessing interactions and overcoming limitations associated with visual assessment of the spectra of such formulations. [ABSTRACT FROM AUTHOR]

Olaparib (OLA) is an anticancer agent that acts by inhibiting the poly (ADP-ribose)-polymerase-I (PARP-I). Due to its low solubility and low permeability, it has been placed as a BCS Class-IV drug and hence its clinical use is limited. In this study, we develop the nanocrystals of OLA as a way to improve its solubility and other performances. The OLA-NCs were prepared by antisolvent precipitation method through homogenization and probe sonication technique using a novel amphiphilic polymeric stabilizer (Soluplus®). Particle characterization resulted approximately 103.13 nm, polydispersity-index was 0.104 with positive zeta-potential of +8.67 mV. The crystal morphology by SEM of OLA-NCs (with and without mannitol) exhibited nano-crystalline prism-like structures as compared to the elongated OLA-pure. The DSC, XRD and FTIR were performed to check the interaction of Soluplus, mannitol and OLA did not exhibit any physical interaction among the OLA, Soluplus® and mannitol that is indicated by the presence of parent wave number peak. Two-fold increased solubility of OLA was found in PBS with Soluplus® from the NCs (69.3 ± 6.2 µgmL−1) as compared to pure drug (35.6 ± 7.2 µgmL−1). In vitro release of drug from OLA-NCs was higher (78.2%) at 12 h at pH 6.8 and relatively lower (53.1%) at pH 1.2. In vitro cellular cytotoxicity and anticancer effects were examined on MCF-7 cells. OLA-NCs were found effectively potent to MCF-7 cells compared with OLA-pure with approximately less than half IC50 value during MTT assay. Estimation of p53, Caspase-3 and Caspase-9 in MCF-7 cells indicated that OLA-NCs have significantly (p < 0.05) increased their expressions. After single oral dose in rats, 12 h plasma drug concentration-time profile indicated approximately 2.06-, 2.29-, 2–25- and 2.62-folds increased Cmax, AUC0-12 h, AUC0-∞ and AUMC0-∞, respectively, from the NCs as compared to OLA-pure. Storage stability indicated that the OLA-NCs was physically and chemically stable at 4 °C, 25 °C and 40 °C up to 6-months. Overall, OLA-NCs were deliberated; its potential feasibility to overwhelm the formulation challenges related to poorly soluble drugs and its future clinical applications. [ABSTRACT FROM AUTHOR]

This study investigates the development of atazanavir-concentrate loaded soft gelatin capsule for achieving enhanced atazanavir (ATV) concentration in plasma, brain, spleen, and lymphatics beneficial in the significant reduction of viral load in HIV infection. For this purpose, ATV-concentrate in the presence and absence of Soluplus with corn oil, oleic acid, tween 80, and propylene glycol was developed. The developed ATV-concentrate was found to have enhanced dispersibility with no signs of precipitation after dilution with simulated G.I fluid as evident from particle size (16.49±0.32 nm) and PDI (0.217±0.02) analysis. The rheological and molecular docking studies explainedthe reduction of viscosity of SuATV-C due to the intermolecular H-bond between ATV and Soluplus that helps to retard crystallization. The shell of the soft gelatin capsule retains its integrity when subjected to a folding endurance test on a texture analyzer depicting that the concentrate did not affect the integrity of the soft gelatin capsule shell. An ex vivo and in vivo pharmacokinetic study in rats revealed that the SuATV-C soft gelatin capsule (SuATV-C SGC) indicated 2.9 fold improvement in rate and extent of permeation and absorption than that of ATV-suspension. The tissue distribution study also exhibited higher drug concentration in the brain (2.5 fold), lymph nodes (2.7 fold), and spleen (1.2 fold) administered with SuATV-C SGC, revealing the overwhelming influence of Soluplus and corn oil. In a nutshell, these studies demonstrated that SuATV-C SGC seems to have the potential to deliver an anti-retroviral drug to the viral sanctuaries for the better management of HIV. [ABSTRACT FROM AUTHOR]

In the body, capillary beds fulfill the metabolic needs of cells by acting as the sites of diffusive transport for vital gasses and nutrients. In artificial tissues, replicating the scale and complexity of capillaries has proved challenging, especially in a three-dimensional context. In order to better develop thick artificial tissues, it will be necessary to recreate both the form and function of capillaries. Here we demonstrate a top-down method of patterning hydrogels using sacrificial templates formed from thermoresponsive microfibers whose size and architecture approach those of natural capillaries. Within the resulting microchannels, we cultured endothelial monolayers that remain viable for over three weeks and exhibited functional barrier properties. Additionally, we cultured endothelialized microchannels within hydrogels containing fibroblasts and characterized the viability of the co-cultures to demonstrate this approach's potential when applied to cell-laden hydrogels. This method represents a step forward in the evolution of artificial tissues and a path towards producing viable capillary-scale microvasculature for engineered organs., (Creative Commons Attribution license.)

Using the time-temperature-transformation diagrams, we demonstrated a correlation between molecular mobility and crystallization in amorphous solid dispersions of nifedipine (NIF) with each polyvinylpyrrolidone vinyl acetate (PVPVA64) and polyvinyl caprolactam polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus). The behavior was compared with the NIF dispersions prepared with each polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose acetate succinate (HPMCAS) [Lalge et al., Mol. Pharmaceutics 2023, 20 (3), 1806-1817]. Each system was characterized by a unique temperature at which the crystallization onset time was the shortest. Below this temperature, a coupling was observed between the α-relaxation time determined by dielectric spectroscopy and crystallization onset time. Above this temperature, the activation barrier for crystallization had a more significant role than molecular mobility. In the solid state, PVP and PVPVA64 dispersion exhibited higher resistance to crystallization than HPMCAS and Soluplus. The role of polymers in inhibiting crystal growth in nucleated systems was discerned by monitoring crystallization following wetting of the amorphous dispersion with the dissolution medium. PVPVA64 and Soluplus dispersions exhibited higher resistance to crystal growth than PVP and HPMCAS.

Objectives: The objective of this research was to enhance the bioavailability of ursolic acid (UA) by preparing multielement amorphous solid dispersion (ASD) systems comprising excipients., Methods: The ASDs were prepared via the solvent evaporation method, characterized by a range of techniques, and investigated with respect to permeability of human colorectal adenocarcinoma cell line (Caco-2) cells monolayers and pharmacokinetics, with comparisons made to the physical mixture and the pure drug., Key Findings: The (UA-choline)-Polyethylcaprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer (Soluplus)-Vitamin E polyethylene glycol succinate (TPGS) ASD demonstrated superior dissolution properties compared to the corresponding binary solid dispersions and ternary solid dispersions (P < .05). The permeability studies of Caco-2 cell monolayers revealed that the ASD exhibited moderate permeability, with an efflux rate that was significantly lower than that of the UA raw material (P < .05). Pharmacokinetic studies in rats demonstrated that the oral bioavailability of the ASD was 19.0 times higher than that of UA (P < .01)., Conclusions: The research indicated that the multielement ASD could be employed as an efficacious drug delivery system for UA. Furthermore, the Soluplus/TPGS/choline combination represents a promising candidate for the fabrication of ASDs that can load weakly acidic and poorly soluble drugs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The present study investigates the preparation of amorphous solid dispersions (ASD) for the ent-kaurane diterpenoid siderol (SDR). Initially, evaluation of the pure drug (isolated from Sideritis scardica) revealed that the API is a non-stable glass former, and hence the selection of a suitable ASD’s matrix/carrier needs special attention. For this reason, four commonly used polymers and copolymers, namely poly(vinylpyrrolidone), copovidone, hydroxypropyl cellulose, and Soluplus® (SOL), were screened via film casting and crystal growth rate measurements. Amongst them, SOL showed the highest SDR’s crystal growth rate reduction, and, since it was also miscible with the drug, it was selected for further testing. In this direction, SDR-SOL ASDs were successfully prepared via melt-quench cooling. These formulations showed full API amorphization, while good physical stability (i.e., a stable SDR amorphous dispersions) were obtained after storage for several months. Finally, evaluation of molecular interactions (with the aid of ATR-FTIR spectroscopy) showed strong H-bonds between SOL and SDR, while the use of molecular dynamics (MD) simulations unraveled the nature of these interactions. Therefore, based on the findings of the present work, SOL seems to be an appropriate matrix/carrier for the preparation of SDR ASDs, although further studies are needed in order to explore its full potentials. [ABSTRACT FROM AUTHOR]

Microneedles have recently emerged as a promising platform for delivering therapeutic agents by disrupting the skin, resulting in improved and high drug delivery via this route. Ibuprofen is widely used topically and orally for chronic pain conditions; to avoid untoward gastric effects, topical application is preferred over the oral route. This study aimed to enhance the solubility of the poorly water-soluble ibuprofen using Soluplus (SP) as a solubilizer and to fabricate dissolving microneedle patches of the drug. The fabricated patches were compared with marketed oral and topical formulations of ibuprofen. A 432-fold increase was observed in the solubility of the drug at 8% SP. The FTIR studies revealed that the drug and polymers were compatible. MNs were of uniform morphology and released the drug in a predictable manner. The in vivo analysis on healthy human volunteers revealed a Cmax of 28.7 µg/mL ± 0.5 with a Tmax of 24 h and a MRT of 19.5 h, which was significantly higher than that observed for commercially available topical formulations. The prepared ibuprofen microneedles have higher bioavailability and MRT at a lower dose (165 µg) as compared to tablet and cream doses (200 mg).

Several literature publications have described the potential application of active pharmaceutical ingredient (API)–polymer phase diagrams to identify appropriate temperature ranges for processing amorphous solid dispersion (ASD) formulations via the hot-melt extrusion (HME) technique. However, systematic investigations and reliable applications of the phase diagram as a risk assessment tool for HME are non-existent. Accordingly, within AbbVie, an HME risk classification system (HCS) based on API–polymer phase diagrams has been developed as a material-sparing tool for the early risk assessment of especially high melting temperature APIs, which are typically considered unsuitable for HME. The essence of the HCS is to provide an API risk categorization framework for the development of ASDs via the HME process. The proposed classification system is based on the recognition that the manufacture of crystal-free ASD using the HME process fundamentally depends on the ability of the melt temperature to reach the API's thermodynamic solubility temperature or above. Furthermore, we explored the API–polymer phase diagram as a simple tool for process design space selection pertaining to API or polymer thermal degradation regions and glass transition temperature-related dissolution kinetics limitations. Application of the HCS was demonstrated via HME experiments with two high melting temperature APIs, sulfamerazine and telmisartan, with the polymers Copovidone and Soluplus. Analysis of the resulting ASDs in terms of the residual crystallinity and degradation showed excellent agreement with the preassigned HCS class. Within AbbVie, the HCS concept has been successfully applied to more than 60 different APIs over the last 8 years as a robust validated risk assessment and quality-by-design (QbD) tool for the development of HME ASDs. [ABSTRACT FROM AUTHOR]

Betulinic acid (3β-Hydroxy-20(29)-lupaene-28-oic acid, BA) has excellent anti-cancer activity but poor solubility and low bioavailability. To improve the antitumor activity of BA, a polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol (PVCL–PVA–PEG) graft copolymer (Soluplus) encapsulated BA micelle (Soluplus-BA) was fabricated. The Soluplus-BA micelles presented a mean size of 54.77 ± 1.26 nm and a polydispersity index (PDI) of 0.083. The MTT assay results showed that Soluplus-BA micelles increased the inhibitory effect of BA on MDA-MB-231 cells, mainly due to the enhanced accumulation of reactive oxygen species (ROS) and the destruction of mitochondrial membrane potential (MMP). Soluplus-BA micelles induced the DNA double-strand breaks (DSBs) as the γH2AX foci increased. Moreover, Soluplus-BA also inhibited the tube formation and migration of human umbilical vein endothelial cells (HUVECs), and inhibited the neovascularization of the chicken chorioallantoic membrane (CAM). This angiogenesis inhibitory effect may be accomplished by regulating the HIF-1/VEGF-FAK signaling pathway. The in vivo study confirmed the improved anti-tumor effect of Soluplus-BA and its inhibitory effect on angiogenesis, demonstrating the possibility of Soluplus-BA as an effective anti-breast cancer drug delivery system.

Microparticles (MPs) and amorphous solid dispersions (SDs) are effective methods to improve the dissolution of insoluble drugs. However, stability is a concern for these two high-energy systems, resulting from high surface area and amorphous polymorph, respectively. As an amphiphilic polymer, Soluplus (SOL) is usually used as a carrier in SDs. In this study, erlotinib microparticles (ERL MPs) and erlotinib solid dispersions (ERL SDs) were prepared with SOL by bottom-up technology and solvent evaporation. The solid-state properties of ERL MPs and ERL SDs were characterized by Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Electron Microscopy (SEM). The ERL MPs existed in a metastable crystal form A while the ERL SDs existed in an amorphous state. Fourier transform infrared spectroscopy (FT-IR) showed that there was a hydrogen bond interaction between the N-H group of ERL and the carbonyl group of SOL in ERL MPs and SDs. The dissolution profiles of ERL SDs and ERL MPs were improved significantly. ERL MPs showed better stability than ERL SDs in accelerated stability test. The discrepant stabilizing effects of polymer SOL in two systems may provide effective ideas for solubilization of insoluble drugs and the stability of drugs after recrystallization. [ABSTRACT FROM AUTHOR]

Objectives: Lumefantrine (LUM) is an antimalarial drug having poor aqueous solubility. The objective was to formulate the solid dispersion of LUM and improve the solubility and dissolution rate. Materials and Methods: Solvent evaporation technique was used to prepare solid dispersions (SDs) with Soluplus® (SOL) using a rotary evaporator. The feasibility of the formation of SD for LUM and SOL was assessed by the Hansen solubility parameter. The drug solubility was analyzed by the HPLC method and the ratio of LUM: SOL was optimized to 1:2. The SD was characterized by DSC, FTIR, XRD and SEM. Results: The results showed that the LUM and SOL had groups that lead to the interaction between them and this led to conversion from crystalline to amorphous form and thus improved the dissolution rate. The solubility of L2 was found to be 135 ± 3.3 µg/mL using the selected dissolution media (0.1 N HCl+1% Myrj 52). The in-vitro antimalarial screening was performed using the P. falciparum 3D7 strain and the in-vitro cytotoxicity test was performed using the Vero cell line. The higher antimalarial efficacy of L2 SD was observed as compared to plain LUM. The selectivity index value of LUM SD depicted its non-toxicity. Stability study was carried out for three months and the SDs were evaluated for the drug content, change in weight and in-vitro drug release. No significant changes were observed after three months in the drug content, SD weight and in-vitro drug release. Thus the L2 SD was found to be stable. Conclusion: The prepared SD improved the solubility as well as the dissolution rate of the drug. [ABSTRACT FROM AUTHOR]

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Introduction: Irbesartan (IBS), an angiotensin II receptor (AT1 subtype) antagonist which blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selective binding to AT1 angiotensin II receptor. It belongs to BCS class II drug (low aqueous solubility and high permeability). Improvement of dissolution characteristics of the drug by formulating is being investigated in the current study. Methods: Solid dispersions (SD) formulations were prepared by the melting fusion technique and nanocomposites (NC) were prepared by a single emulsion technique. Eight batches of SD and three batches of NC were formulated in three ratios of drug to polymer (1:1, 1:2, and 1:3). The batches were evaluated for equilibrium solubility studies, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), field emission SEM (FESEM), transmission electron microscopy (TEM), and in vitro dissolution studies. Results: Solubility studies revealed maximum solubility at a 1:2 ratio of solid dispersions and a 1:1 ratio of nanocomposites. No drug-polymer interaction was observed in FTIR results. DSC, SEM, and XRD analysis revealed changes in drug crystallinity i.e. conversion to the amorphous state of drugs. Nanosize of particles in the NC1 batch was confirmed in TEM studies. Solid dispersions and nanocomposites showed significant enhancement of dissolution in comparison to that of the pure drug (100% drug release in approximately 1 hour). Conclusion: Nanocomposites proved superior carriers to solid dispersions in terms of the dissolution enhancement. Further, in vivo studies indicated that the induction of systolic and diastolic blood pressure in the optimized formulation (NC1) was significantly decreased in comparison to the disease control group (P

Background and purpose: This study aimed at preparation of solid dispersions in order to enhance dissolution of poorly water-soluble atorvastatin using supercritical CO2 technology. Atorvastatin has poor bioavailability of 12%, mainly due to poor water solubility and dissolution. Dispersion of drugs in various hydrophilic carriers using supercritical fluid technology has been found to be an outstanding method to prepare solid dispersion. Experimental approach: Four different polymers were employed. These were polyvinyl pyrrolidone K30 (PVP), polyethylene glycol 6000 (PEG), Soluplus® and chitosan. Full physicochemical characterizations were performed in addition to in vitro dissolution study. Findings / Results: The used polymers enhanced the dissolution rate of atorvastatin. However, supercritical parameters affected the dissolution profile and drug loading efficiency of the prepared dispersions. High performance liquid chromatography assay indicated the stability of the prepared PEG, Soluplus® andchitosan-based dispersions. On the other hand, PVP solid dispersions were not stable and formed sticky paste. Powder X-ray diffraction showed similar patterns for PEG-based dispersions after exposure to storage condition, while the intensity of atorvastatin peaks increased after three months of storage of Soluplus® and chitosan dispersions. Conclusion and implications: Supercritical fluid technology proved to have great potential to prepare dispersions for biopharmaceutics classification system (BCS) class II drugs. Dissolution enhancement of atorvastatin was achieved through successful preparation of polymeric dispersions of the drug using the supercritical technology without further addition of solvents.

The quantification of both polymer and drug during the dissolution of an amorphous solid dispersion (ASD) in aqueous media arouses great interest and may aid in the formulation. However, the available quantification methods for polymer excipients are limited, expensive, and challenging compared to drugs. In this work, a size exclusion chromatography method (HPLC-SEC) was developed and validated to determine the concentration of a frequently used polymer excipient, Soluplus® (Sol). In order to develop a method for the quantification of dissolved Soluplus®, two methods (SEC-UV and SEC-RID) with two injection volumes were tested with standard solutions of three different batches of Soluplus. The developed HPLC-SEC-UV method showed acceptable linearity (R 2 > 0.9990) for all batches of Soluplus, good accuracies above a concentration of 0.1 mg/mL (coefficient of variation < 2 %), relatively good precision at a concentration of 0.1 mg/mL (coefficient of variation < 2.5 %), and high recoveries at a concentration of 0.75 mg/mL (coefficient of variation < 0.5 %). The presence of Felodipine (Fel) and Lumefantrine (Lum) in the liquid media did not interfere with Soluplus quantification. The use of various surfactants, such as Tween® 80, Tween® 20, Span® 80, Span® 20, Kolliphor® TPGS, and sodium lauryl sulphate at a low concentration (0.005 mg/mL) did not show any effect on Soluplus® and did not interfere with Soluplus® quantification with any of the Soluplus batches. The addition of lithium bromide (LiBr) to the mobile phase within a concentration range of 0.05-1.0 M did not improve Soluplus® quantification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Soluplus is a polymer that has been explored to prepare nanocomposites for pulmonary drug delivery and is non-toxic. However, its aerosolization attributes when spray-dried have not been investigated. Hence, this work aimed to investigate the aerosol performance of soluplus-based spray-dried powders. In addition, the potential use of leucine to improve the aerosolization of such particles was also investigated by including leucine at 10 or 20% w/w. 4% w/w salbutamol was used as a model drug in all the formulations primarily to aid quantification during aerosolization evaluation and for assessing the interaction between the drug and soluplus using infrared spectroscopy with the multivariate analysis approach of principal component analysis (PCA). Three formulations (4% salbutamol/96% soluplus, 4% salbutamol/86% soluplus/10% leucine, 4% salbutamol/76% soluplus/20% leucine) were prepared. The formulations were characterized in terms of solid-state, water content, particle size/morphology, and aerosolization. Similarly, two additional formulations (14% salbutamol/86% soluplus and 24% salbutamol/76% soluplus) were prepared to assess potential non-covalent interactions between salbutamol and soluplus. The formulations with only salbutamol and soluplus were amorphous, as evident from X-ray diffraction. Leucine was crystalline in the formulations. All the spray-dried formulations were irregular spheres with surface corrugation. The 96% soluplus powder showed an emitted fraction (EF) and fine particles fraction (FPF) of 91.9 and 49.8%, respectively. The inclusion of leucine at 10% did not increase the EF; however, an increase in FPF (69.7%) was achieved with 20% leucine. PCA of the infrared spectra suggested potential non-covalent interactions between salbutamol and soluplus. It hinted at the potential involvement of ketone groups of the excipient. This study concludes that soluplus-based spray-dried powder with or without leucine can potentially be utilized for pulmonary drug delivery. In addition, PCA can effectively be utilized in assessing interactions and overcoming limitations associated with visual assessment of the spectra of such formulations.

Soluplus (Sol) is an amphiphilic graft copolymer capable of forming self-assembled micelles and L-ascorbyl 2,6-dipalmitate (ASC-DP) aggregates spontaneously to form micelles. Micelles are used as drug carriers and can nanoparticulate drugs that are poorly soluble in water, such as minoxidil. The study aimed to prepare minoxidil-encapsulated nanoparticles using Sol/ASC-DP and evaluate their potential for targeted skin application. Sol/ASC-DP nanoparticles or Sol/ASC-DP with minoxidil were prepared using the hydration method, and physical evaluations were carried out, including assessments of particle size and zeta potential. Particle structure was evaluated by transmission electron microscopy (TEM) and ¹H-nuclear magnetic resonance spectra to assess particle stability and perform functional evaluations in skin penetration tests. TEM images showed spherical micelle-like particles of approximately 100 nm for Sol/ASC-DP at a 9:1 ratio and of approximately 80 nm for Sol/ASC-DP with incorporated minoxidil at a 9:1:0.5 ratio. Changes were also observed in the solid state, suggesting a hydrophobic interaction between Sol and ASC-DP. In addition, evaporated microparticles (Sol/ASC-DP/minoxidil = 9/1/0.5) improved the skin permeability of minoxidil. These results suggest that Sol/ASC-DP nanoparticles form a stable new nanoparticle due to hydrophobic interactions, which would improve the skin permeability of minoxidil. [ABSTRACT FROM AUTHOR]

[Display omitted] • Various mesoporous silica grades were used in ternary amorphous solid dispersions. • Felodipine was the model drug and hot melt extrusion as the preparation process. • Spatial distributions of the drug & intermolecular interactions were investigated. • The release rate and release profile were governed by a complex mechanism. • The drug stability was significantly enhanced through integration of MPSI grades. In this work, the application of various mesoporous silica grades in the preparation of stabilized ternary amorphous solid dispersions of Felodipine using hot melt extrusion was explored. We have demonstrated the effectiveness of mesoporous silica in these dispersions without the need for any organic solvents i.e., no pre-loading or immersion steps required. The physical and chemical properties, release profiles of the prepared formulations and the surface concentrations of the various molecular species were investigated in detail. Formulations containing 25 wt% and 50 wt% of Felodipine demonstrated enhanced stability and solubility of the drug substance compared to its crystalline counterpart. Based on the Higuchi model, ternary formulations exhibited a 2-step or 3-step release pattern which can be ascribed to the release of drug molecules from the organic polymer matrix and the external silica surface, followed by a release from the silica pore structure. According to the Korsmeyer-Peppas model, the release rate and release mechanism are governed by a complex quasi-Fickian release mechanism, in which multiple release mechanisms are occurring concurrently and consequently. Stability studies indicated that after 6 months storage of all formulation at 30% RH and 20 °C, Felodipine in all formulations remained stable in its amorphous state except for the formulation comprised of 40 wt% Syloid AL-1FP with a 50 wt% drug load. [ABSTRACT FROM AUTHOR]

Objectives Current treatment for autonomic dysreflexia (AD) involves rupturing a liquid-filled soft capsule of nifedipine to aid rapid drug release and absorption, however, this application is not covered under the manufacturer's license. The objective of the current work was to design a rapidly dissolving solid dosage formulation for the treatment of AD as an alternative to the off-license "bite and swallow" use of currently available commercial products. Methods Amorphous solid dispersions (ASDs) of nifedipine were prepared by spray-drying using three different polymers: hydroxypropyl methyl cellulose (HPMC), polyvinyl pyrrolidone (PVP) and polyvinyl caprolactam--polyvinyl acetate--polyethylene glycol (Soluplus), at a 15% w/w drug loading and were formulated and compressed into tablets. Dissolution testing was performed in the paddle dissolution apparatus using either a monophasic or biphasic medium. Key findings The PVP--nifedipine ASD tablets exhibited rapid dissolution, with 35% of the total nifedipine dose dissolving within 15 min in the monophasic dissolution medium. The HPMC--nifedipine ASD exhibited a very slow dissolution, while the Solupus--nifedipine system exhibited no nifedipine release over 120 min. When tested in the biphasic dissolution medium, the PVP--nifedipine ASD tablets exhibited a release profile comparable to that of the pre-split/ruptured nifedipine soft capsule product. Conclusions This study demonstrates that a nifedipine--PVP ASD is a promising formulation strategy in the treatment of AD. [ABSTRACT FROM AUTHOR]

Infections of the eye are among the leading causes of vision impairment and vision loss worldwide. The ability of a drug to access the anterior parts of the eye is negligible after systemic administration. Effective drug delivery to the eye is a major challenge due to the presence of protective mechanisms and physiological barriers that result in low ocular availability after topical application. The main purpose of this work was the improvement of the corneal and conjunctival permeation of the antibiotic Ciprofloxacin, a wide spectrum antibiotic used for the most common eye infection, using a self-dissolving polymeric film. Films were prepared by the solvent casting technique, using polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer (Soluplus), polyvynyl alcohol, and propylene glycol. Films were homogeneous in drug content and thickness, as demonstrated by adapting the Swiss Roll technique followed by microscopy observation. These films proved in vitro to control the release of the Ciprofloxacin. Ex vivo permeability studies using Franz diffusion cells and porcine cornea and sclera showed an effective permeability of the drug without inducing irritation of the tissues. Films swelled in contact with artificial tears forming an in situ gel over 20 min, which will improve drug contact and reduce the need of multiple dosing. The antibiotic activity was also tested in vitro in five types of bacterial cultures, assuring the pharmacological efficacy of the films. The developed films are a promising drug delivery system to topically treat or prevent ocular infections. [ABSTRACT FROM AUTHOR]

Introduction: Artemether, a BCS class IV drug (poorly water soluble and poorly permeable, less bioavailability) but is found to be effective against falciparum malaria. Preparation of water soluble formulation could be the technique to improve bioavailability of such drug. The most ideally used technique to enhance the solubility and dissolution of poorly water soluble drugs is Solid dispersion method. Method: The objective of the study was to enhance the solubility and dissolution rate of Artemether by preparing solid dispersions using Soluplus, at different ration of 1:1, 1:2, 1:3 and 1:4 using spray drying technology. Prepared Solid dispersions were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Results: The spray-dried solid dispersions found to be having less crystallinity and showed higher dissolution rates. Solubility study data showed the optimum drug/Soluplus ratio to be 1:3. The dissolution studies of Solid dispersions in 1.2 pH and 6.8 pH buffer showed higher drug release as compared to pure drug. Conclusion: Thus we conclude that an amorphous solid dispersion of Artemether could be a better option for enhancing the dissolution rate of drug. [ABSTRACT FROM AUTHOR]

The present study involved enhancement of Meloxicam (MX) oral absorption for rapid onset of therapeutic action. A challenging approach using hot-melt-extrusion technique (HME) for production of stable novel preparation of MX pellets was successfully proposed. Manipulating HME processing parameters (barrel-temperatures and screw-speed) and proper polymer(s) selection (Soluplus, a combination of Soluplus/Poloxamar and Polyethylene Glycol 6000) were the main strategies involved for productive extrusion of MX. Evaluation of MX solid-state (TGA, DSC and PLM), absolute percent crystallinity, in-vitro dissolution (in acidic/aqueous pHs), and stability testing in accelerated conditions up to 6-months as well as a long-term shelf for 36-months were performed. A comparative bioavailability study of selected MX-Pellets was carried-out against the innovator product (Mobic®) in 6 healthy volunteers under fed-conditions. TGA, DSC and PLM analyses proved the dispersion of MX in amorphous-state within polymeric matrix by HME. MX/Soluplus pellets exhibited the lowest crystallinity % and best dissolution performance among other polymers in both pHs. In addition, presence of Soluplus safeguards final pellets stability under different storage conditions. MX rate of absorption (Tmax) from Soluplus-based pellets attained a value of 45 min, which was 6-times faster than Mobic® (4.5 hr). A promising oral MX formula prepared by HME was successfully developed with a rapid onset of analgesic action (Tmax of 45 mins; almost 2-times faster than reported intramuscular injection), hence appropriate in the early relief of pain associated with rheumatoid arthritis and osteoarthritis. Moreover, the proposed formula was physico-chemically stable up to 36 months of shelf-life storage. [ABSTRACT FROM AUTHOR]

To enhance the dissolution and oral bioavailability of telmisartan (TMS), a poorly water-soluble anti-hypertensive drug, a supersaturable self-microemulsifying drug delivery system (SuSMEDDS) was developed. Amorphous alkalinized TMS (AAT) was formulated into a SMEDDS, composed of Capmul® MCM (oil), Cremophor® RH40 (surfactant), and tetraglycol (co-surfactant). Although the SMEDDS was rapidly dissolved (>80% within 5 min) in a limited condition (500 mL, pH 6.8), drug precipitation was observed over time, resulting in a decrease in dissolution levels. The precipitation was due to drug recrystallization, as determined by differential scanning calorimetry and powder X-ray diffraction analyses. Several polymers, including Soluplus® (SOL), were screened as precipitation inhibitors; ultimately, SuSMEDDS-SOL was prepared by admixing SOL and the SMEDDS at a 5:100 (w/w) ratio. SuSMEDDS-SOL was superior in terms of dissolution efficiency (>90% over 2 h) and dissolution-retaining time (no precipitation over 2 h). An in vivo pharmacokinetic study in rats revealed that the oral bioavailability of SuSMEDDS-SOL was 4.8-, 1.3-, and 1.2-fold greater than those of the TMS suspension, AAT solution, and SMEDDS, respectively. Therefore, SuSMEDDS-SOL is a promising candidate to enhance the dissolution and oral bioavailability of TMS. [ABSTRACT FROM AUTHOR]