Development and Evaluation of Micropelleted Sustained-Release Suppositories of Terbutaline Sulfate

Abstract

Terbutaline sulfate (TS), a β2 agonist, was fabricated in the form of micropelleted sustained-release suppositories. Micropellets of TS using Eudragit RS100 were prepared by emulsification-solvent evaporation technique and were incorporated into suppositories (PEG 4000 as base) by fusion method. Physical, in vitro and in vivo evaluations were carried out for both conventional (PEG 4000 base) and micropelleted sustained-release suppositories and were compared. Micropellets were scanned using electron microscopy to see the surface structure before and after the in vitro dissolution.     

Differential Thermal Analysis of Polyethylene Glycol and Glycerol Monostearate Suppository Bases Containing Theophylline

Abstract

Water soluble polyethylene glycol 4000 (PEG4) suppositories were prepared containing 4% (w/w) theophylline. Various concentrations of polyethylene glycol 1000 (PEG1) and glycerol monostearate (GMS) were also added. Differential thermal analysis (DTA) of the PEG4 and PEG1 combination suppositories showed no melting endotherm for theophylline. But when theophylline concentration in the base was 12% (w/w) and above, sharp endothermic peak of theophylline was obtained. In contrast, when GMS was added as a base material above 50% (w/w) with PEG4, the melting endotherm of theophylline (4%, w/w) appeared at 273-274°C. The melting endotherm of the suppository bases increased up to 2 to 4°C due to storage at 4°C for six months.     

Rheology and Filling Characteristics of Particulate Dispersions in Polymer Melt Formulations for Liquid Fill Hard Gelatin Capsules

Abstract

The rheology and capsule filling properties of molten excipients, Dynafill, Dynasan-114, Lutrol-F68, and polyethylene glycols (PEG) 6000, 8000, 10,000, and 20,000 have been investigated. Lactose (α-monohydrate) was selected as a model particulate solid with low solubility in PEG in order to investigate the effects of disperse phase particle size, concentration, and PEG molecular weight on rheology and capsule filling properties of these systems. All excipients behaved as Newtonian fluids between 65 and 90°C, which was chosen as a possible temperature range for liquid filling of hard gelatin capsules. The excipients, apart from Dynasan-114 and PEG 20,000, showed satisfactory capsule filling properties at 70°C using a semiautomatic filling machine. Dynasan-114 (viscosity = 0.012 Pass at 70°C) leaked from the seals between the hopper and pump of the filling machine, whereas PEG 20,000 (viscosity = 24 Pas at 70?C) showed bridging of the molten polymer between successive capsule bodies during the filling process. The effect of disperse phase (lactose) particle size and concentration, and continuous phase (PEG) molecular weight on the apparent viscosity and filling properties of the non-Newtonian dispersions were investigated at 70°C. Satisfactory filling of the dispersions was achieved at 70°C up to a limiting concentration of disperse phase which was dependent upon disperse phase particle size and continuous phase molecular weight, and corresponded to a pronounced increase in apparent viscosity of the dispersion.     

Preparation and characterization of progesterone dispersions using supercritical carbon dioxide

Context: Supercritical fluid methods offer an alternative to conventional mixing methods, particularly for heat sensitive drugs and where an organic solvent is undesirable.

Objective: To design, develop and construct a unit for the particles from a gas-saturated suspension/solution (PGSS) method and form endogenous progesterone (PGN) dispersion systems using SC-CO₂.

Materials and methods: The PGN dispersions were manufactured using three selected excipients: polyethylene glycol (PEG) 400/4000 (50:50), Gelucire 44/14 and D-α-tocopheryl PEG 1000 succinate (TPGS). Semisolid dispersions of PGN prepared by PGSS method were compared to the conventional methods; comelting (CM), cosolvent (CS) and physical mixing (PM). The dispersion systems made were characterized by Raman and Fourier transform infrared (FTIR) spectroscopies, X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), PGN recovery, uniformity and in vitro dissolution, analyzed by high-performance liquid chromatography (HPLC).

Results: Raman spectra revealed no changes in the crystalline structure of PGN treated with SC-CO₂ compared to that of untreated PGN. XRPD and FTIR showed the presence of peaks and bands for PGN confirming that PGN has been incorporated well with each individual excipient. All PGN dispersions prepared by the PGSS method resulted in the improvement of PGN dissolution rates compared to that prepared by the conventional methods and untreated PGN after 60 min (p value?Conclusion: The novel PGN dispersions prepared by the PGSS method offer the great potential to enhance PGN dissolution rate, reduce preparation time and form stable crystalline dispersion systems over those prepared by conventional methods.     

Rheological investigation and its correlation with permeability coefficient of drug loaded carbopol gel: influence of absorption enhancers

Context: The present study was planned to investigate the effect of absorption enhancers on the microstructure of Losartan potassium gel and hence its influence on the diffusion of Losartan potassium across nasal mucosa.

Method: Losartan potassium loaded carbopol gel (1% w/v) with and without absorption enhancers was prepared. Polyethylene glycol (PEG) 4000 and ethanol were used as absorption enhancers. Microstructural elucidation of prepared gels was done using shear rheology. Ex vivo drug release studies were performed on the prepared gels.

Results: It was observed that the absorption enhancers PEG 4000 and ethanol altered the gel microstructure. The prepared gels were viscoelastic in nature suggesting their suitability for topical application. Permeability coefficient of Losartan potassium loaded into gels was found to be inversely proportional to the storage modulus. Thus increase in storage modulus lead to slow drug diffusion.

Conclusion: The current study emphasizes on the fact that selection of polymeric carrier for nasal drug delivery and/or absorption enhancer strongly influence the microstructure of the gel and hence the pharmaceutical performance of the formulation.     

Development and Evaluation of Micropelleted Sustained-Release Suppositories of Terbutaline Sulfate

Terbutaline sulfate (TS), a β2 agonist, was fabricated in the form of micropelleted sustained-release suppositories. Micropellets of TS using Eudragit RS100 were prepared by emulsification-solvent evaporation technique and were incorporated into suppositories (PEG 4000 as base) by fusion method. Physical, in vitro and in vivo evaluations were carried out for both conventional (PEG 4000 base) and micropelleted sustained-release suppositories and were compared. Micropellets were scanned using electron microscopy to see the surface structure before and after the in vitro dissolution.     

Differential Thermal Analysis of Polyethylene Glycol and Glycerol Monostearate Suppository Bases Containing Theophylline

Water soluble polyethylene glycol 4000 (PEG4) suppositories were prepared containing 4% (w/w) theophylline. Various concentrations of polyethylene glycol 1000 (PEG1) and glycerol monostearate (GMS) were also added. Differential thermal analysis (DTA) of the PEG4 and PEG1 combination suppositories showed no melting endotherm for theophylline. But when theophylline concentration in the base was 12% (w/w) and above, sharp endothermic peak of theophylline was obtained. In contrast, when GMS was added as a base material above 50% (w/w) with PEG4, the melting endotherm of theophylline (4%, w/w) appeared at 273-274°C. The melting endotherm of the suppository bases increased up to 2 to 4°C due to storage at 4°C for six months.     

In vitro digestion kinetics of excipients for lipid-based drug delivery and introduction of a relative lipolysis half life

Background: Lipid-based drug delivery systems are widely used for enhancing the solubility of poorly water soluble drugs in the gastro-intestinal tract. Following oral intake, lipid systems undergo digestion in the stomach as well as the intestine. Lipolysis is here a complex process at the oil/water interface, influenced by numerous factors.

Purpose: To study the digestibility of nine excipients often used in lipid-based drug delivery systems. In addition, we introduced a mathematical model to describe in vitro lipolysis kinetics. A relative lipolysis half life was defined using the reference excipient medium-chain triglycerides.

Methods: Using pH-stat equipment, the NaOH consumption was determined in an in vitro lipolysis assay.

Results: We identified two classes of excipients. Some additives were partially hydrolysed, whereas other excipients displayed complete lipolysis. For the latter class, a simplified mathematical model provided a good first approximation of initial lipolysis kinetics.

Conclusions: Digestion characterization of excipients is important for the development of lipid-based delivery systems. The applied kinetic model and the concept of a relative lipolysis half life seemed to be promising tools for comparing in vitro lipolysis results.     

Sildenafil vaginal suppositories: preparation,characterization, in vitro and in vivo evaluation

Aim: The main objective was to investigate the in vitro release profile/kinetics, and in vivo plasma pharmacokinetics (PK) and organ biodistribution (BD) of the prepared sildenafil vaginal suppositories (SVS).

Methods: Suppositories containing 25?mg of sildenafil were prepared by the cream melting technique using Witepsol H-15 as a suppository base. The suppositories were characterized for weight variation, content uniformity, hardness, disintegration time and crystallinity change. The in vitro dissolution in pH 4.5, and in vivo plasma PK and organ BD of sildenafil from SVS in female Sprague Dawley rats, were also investigated.

Results: The mean weight variation, content uniformity, hardness and disintegration time of the prepared SVS were 1.127?±?0.020?g, 98.25?±?2.50%, 2.5?±?0.08?kg and 9?±?1.0?min, respectively. The release of sildenafil from the SVS was more than 90% at 30?min, with a release kinetic of Hixson--Crowell model and non-Fickian diffusion (n?=?0.464). The plasma PK study demonstrated a significantly lower C_max (～10 times) and AUC_0–24?h (～13 times) of sildenafil in plasma following intravaginal (IVG) administration of suppositories compared to oral (PO) administration of sildenafil solution. Nevertheless, the organ BD study showed a phenomenally higher C_max (～40 times) and AUC_0–24?h (～20 times) of sildenafil in uterus following IVG administration of suppositories than PO administration of sildenafil solution.

Conclusion: This study demonstrated enhanced sildenafil exposure in the uterus following IVG administration of SVS, which could be used to target the uterus for therapeutic benefits.     

Release Characteristics and Bioavailability of Norfloxacin from Suppository Bases

Abstract

The in vitro release of norfloxacin (a new broad spectrum antimicrobial agent whose pharmacokinetics are characterised by varied gastrointestinal absorption and irregular plasma level) from different suppository bases was studied in order to obtain suitable formulation with good release and satisfactory drug concentrations in plasma. The bioavailability of suppositories containing 200 mg drug made from the bases that showed the best in vitro release was investigated. The release rate was in the order of PEG 400, 1540, 4000 mixture in ratio of 20: 33: 47 respectively > Witepsol H1S > Witepsol W 35 > Witepsol E 75. Addition of Tween 20, Tween 80 and Myrj 45 to the Witepsol members greatly increased the release rate especially at surfactant concentration of 5 × 10 mol.g. of the drug.     

Dissolution of Suppositories III: Effect of Insoluble Polyvinylpyrrolidone on Acetaminophen Release

Abstract

Previously reported studies from this laboratory have demonstrated the usefulness of a new apparatus for suppository dissolution study. Acetaminophen suppositories gave slow release and it was posited that addition of a disintegrating agent commonly used in tablet manufacture would increase this release rate. To test the hypothesis, four PEG blends were used as bases as in the previous studies. Each contained 320 mg acetaminophen and 1%, 5%, or 10% of insoluble polyvinylpyrrolidone (Polyplasdone XL^R). One thousand milliliters of phosphate buffer, pH 8.0 to approximate rectal pH was employed as the dissolution media and maintained at 37.5°. A constant agitation rate of 2 5 and 50 rpm was used. Acetaminophen was assayed spectrophotometrically at 243 nm. Comparative dissolution profiles at the various agitation rates and with the concentrations of polyvinylpyrrolidone were developed. Addition of insoluble polyvinylpyrrolidone increased the dissolution rate constant and dissolution half-times at the two agitation rates. While the disintegration aid increased release, this release was not linear with respect to disintegrating agent concentration.

Release of acetaminophen from suppositories and the bioavailability of acetaminophen Erom suppository bases have not received much study. Feldman reported that the rate of bioavailability of suppositories was extremely variable and might not produce a clinically noted response (1). Maron and Ickes, however, reported that acetaminophen suppositories were clinically as effective an antipyretic as were tablets (2).

Pagay, et al. studied the influence of the vehicle on the bioavailability of acetaminophen suppositories using a modified beaker method with a media of pH 7.0 and an agitation of 25 rpm (3). These researchers correlated the dielectric constant of the base to acetaminophen bioavailability. Commercial suppositories were not discussed.

A recent report by Palmieri (4) discussed release of acetaminophen from laboratory prepared PEG bases and commercially available suppositories. Dissolution half-times for laboratory prepared suppositories at 50 rpm ranged from 8 minutes for Base A to 22 minutes for Base D. The commercially available acetaminophen suppositories had a dissolution half-time of 90 minutes at 50 rpm. Because of these apparently slow release rates, it was posited that addition of a disintegrating agent would increase the release of acetaminophen from the polyethylene glycol base sup-positores. Polyplasdone XLR, (5) a crosslinked insoluble homopolymer of n-vinyl-2-pyrrolidone was used in an attempt to increase the release rate.     

Formulation of Suppositories Containing Imipramine and Clomipramine Chlorhydrates

Abstract

Imipramine chlorhydrate and clomipramine chlorhydrate could be formulated into suppositories forms. Their ability to be administered by the rectal way was assessed by the measurement of their hydrophilic/lipophilic partition coefficient and their diffusion coefficient with the Strieker's apparatus. The suppositories were formulated with several halfglycerides excipients. The selection of the formulae was carried out by using the following physicochemical tests: rheological behaviour, melting point, liquefaction time with the Krowczynski's technique, disintegration time with the Munzel's method, spreading area, hardness, kinetic of release. The bioavailability of the suppositories evaluated on rabbits compared to an intravenous injection was 28% for Clomipramine and 25 % for Imipramine.

A clinical assay was carried out with three inpatients, The plasmatic levels of the drugs and the clinical efficiency were in the same range as previous data reported in the literature for oral forms.     

Design and evaluation of D-α tocopheryl polyethylene glycol 1000 succinate emulsified poly-ϵ-caprolactone nanoparticles for protein/peptide drug delivery

Background: Incorporation of proteins/peptide drugs into nanoparticulate drug delivery system is one of the effective approaches to increase the stability of protein/peptide drugs against enzymatic degradation, to release them in a controlled fashion and to achieve site-specific drug delivery.

Objective: Our goal was to design and evaluate poly-?-caprolactone (PCL) nanoparticles using bovine serum albumin (BSA) as a model protein. d-α-tocopheryl polyethylene glycol 1000 (vitamin E TPGS) was used as an emulsifier in the fabrication of these nanoparticles.

Methods: Double emulsion solvent evaporation method was employed to formulate BSA-loaded PCL nanoparticles and the nanoparticles thus prepared were further characterized.

Results: The size of BSA-loaded PCL nanoparticles were in the range of 400–500?nm with a polydispersity index (PDI) of 0.195 and zeta potential was about ?28.6 mV. Scanning electron microscopy (SEM) confirmed the presence of smooth and spherical surface of nanoparticles. Encapsulation efficiency was about 85% and a yield of 70–75% was attained. BSA was released in a biphasic pattern with an initial 20% release within 2?h followed by a slower release patter over 5 days. Flow cytometry and fluorescence microscopy was used to study the uptake of these nanoparticles. Circular dichroism (CD) results showed that there was no significant effect of formulation conditions on the secondary structure of BSA.

Conclusion: Based on the results obtained, these TPGS-emulsified PCL nanoparticles proved to be potential carriers for the delivery of protein/peptide drugs.     

Controlled Release Salbutamol Sulphate Molded Tablets Using Eudragit Retard

Abstract

Permeable acrylic resins were used as efficient retarding materials to prepare controlled release salbutamol sulphate molded tablets. The formulation is simple, efficient, economic and is easily shaped into molded tablets. The effects of two types of acrylic resins, namely: Eudragit RL100 ad Eudragit RS100 in concentrations 1, 2 and 5% w/w on the physical characteristics as well as on the in vitro release patterns of salbutamol sulphate from molded tablets prepared with either polyethylene glycol (PEG) 4000 or 6000 were studied. It was revealed that, as the molecular weight of the PEG increased, the hardness of the tablets increased. Considerable retardation in the drug release was observed by using Eudragit RS100 as compared to Eudragit RL100. The formulation prepared with PEG 6000 and 5% Eudragit RS100 produced much more release time prolongation than the other tested formulations. On the other hand, tablets prepared by the direct compression technique produced a faster release of salbutamol sulphate than those prepared by molding.     

Influence of additives on melt viscosity,surface tension,and film formation of dry powder coatings

Background: Limited information on thermally cured dry-powder coatings used for solid dosage forms has been available in the literature. Aim: The aim of this study was to characterize the film formation process of Eudragit® L 100-55 dry-powder coatings and to investigate the influence of film additives on melt viscosity and surface tension. Methods: The coating process employed no liquids and the plasticizer was combined with the polymer using hot melt extrusion. Thermoanalytical methods including differential scanning calorimetry and thermogravimetric analysis (TGA) were used to investigate the thermal properties of the dry-coating formulations. The rheological behavior of the coating formulations were characterized with the extrusion torque, and the surface energy parameters were determined from contact angle measurements. The influence of the level of triethyl citrate (TEC) as plasticizer and polyethylene glycol (PEG) 3350 in the polymer film on film formation was investigated using a digital force tester. Results: TGA confirmed thermal stability of all coating excipients at the investigated curing conditions. Increasing TEC levels and the addition of PEG 3350 as a low melting excipient in the coating reduced the viscosity of the polymer. Plasticization of the polymer with TEC increased the surface free energy, whereas the admixture of 10% PEG 3350 did not affect the surface free energy of Eudragit® L 100-55. The spreading coefficient of the polymers over two sample tablet formulations was reduced with increasing surface free energy. During the curing process, puncture strength, and elongation of powder-cast films increased. The effect of curing time on the mechanical properties was dependent on the plasticizer content. Conclusions: The incorporation of TEC and PEG 3350 into the Eudragit® L 100-55 powder coating formulation improved film formation. Mechanical testing of powder-cast films showed an increase of both elongation and puncture strength over the curing process as criterion for polymer particle fusion, where film formation progressed faster at high plasticizer levels.     

Mucoadhesive nanoliposomal formulation for vaginal delivery of an antifungal

Context: Ciclopirox olamine (CPO) is indicated in the treatment of vaginal fungal infections. The frequent and large dosing of available vaginal CPO creams gives rise to poor compliance amongst females. In such a situation a delivery system capable of providing sustained release of CPO is warranted and can be realized through incorporation of its liposomal formulation into a mucoadhesive gel base. The liposomal formulation would offer sustained release whereas mucoadhesive gel would prolong the contact with vaginal wall; thus avoiding frequent and large dosing.

Objective: The present study aimed at investigating mucoadhesive liposomal CPO gel for vaginal use.

Method: The study embarked on evaluating liposomal CPO and its Carbopol 974^®P gel for stability at vaginal pH, release profile, rheological characteristics, mucoadhesive behavior and finally antifungal activity.

Results: The results revealed that CPO liposomes were stable at vaginal pH; its Carbopol gel released 58.75?±?6.4% of CPO at the end of 24?h which suggested sustained release. Rheology via viscometric, oscillatory stress sweep and oscillatory frequency sweep testing of the gel, studied at different temperatures and under different dilutions with vaginal fluid simulant testified pseudoplastic behavior of the gel. It also pointed towards the predominance of elastic behavior of the gel at all the dilutions. The gel exhibited good mucoadhesivity to sheep vaginal tissue. Furthermore, CPO entrapped in liposome too displayed antifungal activity.

Conclusion: The study undertaken recommended Carbopol 974^®P gel loaded with CPO liposomes as a potential delivery system for treatment of fungal vaginal infections.     

Preparation of Codeine-Resinate and Chlorpheniramine-Resinate Sustained-Release Suspension and its Pharmacokinetic Evaluation in Beagle Dogs

ABSTRACT

Using ion exchange resins (IERs) as carriers, a dual-drug sustained release suspension containing codeine, and chlorpheniramine had been prepared to elevate drug safety, effectiveness and conformance. The codeine resinate and chlorpheniramine resinate beads were prepared by a batch process and then impregnated with Polyethylene glycol 4000 (PEG 4000), respectively. The PEG impregnated drug resinate beads were coated with ethylcellulose as the coating polymer and di-n-butyl-phthalate as plasticizer in ethanol and methylene chloride mixture by the Wurster process. The coated PEG impregnated drug resinate beads were dispersed in an aqueous suspending vehicle containing 0.5% w/w xanthan gum and 0.5% w/w of hydroxypropylmethylcellulose of nominal viscosity of 4000 cps, obtaining codeine resinate and chlorpheniramine resinate sustained-release suspension (CCSS).

Codeine phosphate and chlorpheniramine maleate were respectively loaded onto AMBERLITE® IRP 69, and PEG 4000 was used to impregnate drug resinate beads to maintain their geometry. Ethylcellulose with di-n-butyl-phthalate in ethanol and methylene chloride mixture for the coating of drug resinate beads was performed in Glatt fluidized bed coater, where the coating solution flow rate was 8–12 g/min, the inlet air temperature was 50–60°C, the outlet air temperature was 32–38°C, the atomizing air pressure was 2.0 bar and the fluidized air pressure was adjusted as required. Few significant agglomeratation of circulating drug resinate beads was observed during the operation. The film weight gained 20% w/w and 15% w/w were suitable for the PEG impregnated codeine resinate and chlorpheniramine resinate beads, respectively. Residual solvent content increased with coating level, but inprocess drying could reduce residual solvent content.

In the present study, the rates of drug release from both drug resinate beads were measured in 0.05M and 0.5M KCl solutions. The increased ionic strength generally accelerated the release rate of both drugs. But the release of codeine from its resinate beads was much more rapid than chloropheneramine released from its resinate beads in the same ionic strength release medium. The drug release specification of the CCSS, where release mediums were 0.05M KCl solution for codeine and 0.5M KCl solution for chlorpheniramine, was established to be in conformance with in vivo performance.

Relative bioavailability and pharmacokinetics evaluation of the CCSS, using commercial immediate-release tablets as the reference preparation, were performed following a randomized two-way crossover design in beagle dogs. The drug concentrations in plasma were measured by a validated LC-MS/MS method to determine the pharmacokinetic parameters of CCSS. This LC-MS/MS method demonstrated high accuracy and precision for bioanalysis, and was proved quick and reliable for the pharmacokinetic studies. The results showed that the CCSS had the longer value of T_max and the lower value of C_max, which meant an obviously sustained release effect, and its relative bioavailability of codeine and chlorpheniramine were (103.6 ± 14.6)% and (98.1 ± 10.3)%, respectively, compared with the reference preparation. These findings indicated that a novel liquid sustained release suspension made by using IERs as carriers and subsequent fluidized bed coating might provide a constant plasma level of the active pharmaceutical ingredient being highly beneficial for various therapeutic reasons.     

Dissolution of Nalidixic Acid Solid Dispersions: Systems of NAL-Inclusion and Linear Polymeric Compounds

Abstract

The solubility and dissolution rate enhancement of nalidixic acid powder, applying solid dispersion technique, with inclusion and linear polymeric compounds were studied. At 100 g/L carrier concentration, the increase in drug solubility was 3.3, 2.0, 1.4 and 1.1 times that of the powdered drug for urea, PEG 4000, PEG 6000 and PVP, respectively. The increase in carrier ratio enhanced the drug dissolution. At four fold carrier concentrations, the amount dissoluted after one hour was 50, 55 mg/L for samples prepared by fusion with urea and PEG 6000, respectively. The coprecipitation with FTP dissoluted 65 mg/L of nalidixic acid after one hour compared to only 27.5 mg/L of powdered drug alone.     

Enhancement of docetaxel solubility using binary and ternary solid dispersion systems

Context: Poor biopharmaceutical properties and toxicities associated with the intravenous formulation of docetaxel (DTX) necessitate the exploration of an alternate oral route of delivery.

Objective: This study aims at enhancing the solubility of poorly soluble drug, DTX with the help of solid dispersion (SD) technique.

Method: DTX SDs were formulated with selected solubilizers, including Kollidon 12PF, Lutrol F68, Soluplus and Hydroxypropyl-β-cyclodextrin in different weight ratios. Freeze-drying method was used to prepare the binary and ternary SDs. Kinetic solubility of the SDs was evaluated in order to select best DTX-solubilizer combination. Best performing combination was then characterized using differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM).

Results and Discussion: Among all SDs tested, Soluplus outperformed all the excipients at equivalent weight ratio. Binary SD of DTX and Soluplus (1:10) resulted in the highest improvement in solubility (362.93?±?11.01?µg/mL). This is approximately a 93-fold increment as compared to the solubility of crystalline DTX (3.9?±?0.2?µg/mL). This exceptional performance can be attributed to solid-state transformation as well as micellization.

Conclusion: Among all the excipients tested, Soluplus dispersion is the most promising candidate for oral formulation development.