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Article

A Quaternary Solid Dispersion System for Improving the Solubility of Olaparib

by
Tae-Han Yun
1,
Jeong-Gyun Lee
1,
Kyu-Ho Bang
1,
Jung-Hyun Cho
2,* and
Kyeong-Soo Kim
1,*
1
Department of Pharmaceutical Engineering, Gyeongsang National University, 33 Dongjin-ro, Jinju 52725, Republic of Korea
2
Department of Pharmaceutical Engineering, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 31116, Republic of Korea
*
Authors to whom correspondence should be addressed.
Solids 2025, 6(1), 1; https://doi.org/10.3390/solids6010001
Submission received: 29 October 2024 / Revised: 14 December 2024 / Accepted: 25 December 2024 / Published: 2 January 2025
(This article belongs to the Special Issue Amorphous Materials: Fabrication, Properties, and Applications)
Browse Figures
Versions Notes

Abstract

:
To improve the low solubility of poorly water soluble olaparib, in the following study, we prepared olaparib-loaded quaternary solid dispersions with hypromellose, Tween 20 or Labrasol, and colloidal silica. The solubility of olaparib with various types of surfactants was evaluated to select the most suitable surfactant to effectively enhance its solubility, and subsequently, olaparib-loaded quaternary solid dispersions were prepared through spray drying. The physicochemical properties of the prepared olaparib-loaded quaternary solid dispersions were investigated using scanning electron microscopy, flowability, powder X-ray diffraction, and Fourier-transform infrared spectroscopy. The particle size of the olaparib-loaded quaternary solid dispersions was smaller and more spherical compared to the olaparib drug powder and maintained an amorphous state, and olaparib exhibited no intermolecular interactions with other excipients within the solid dispersion. Additionally, they exhibited enhanced flow properties compared to the olaparib drug powder. The results of subsequent kinetic solubility tests and dissolution tests demonstrated that the surfactant influenced the enhancement of the solubility and drug release of olaparib. Therefore, olaparib-loaded quaternary solid dispersions, characterized by enhanced solubility, will be beneficial for the oral delivery of poorly soluble olaparib.

1. Introduction

The pharmaceutical industry is currently facing significant challenges, with 90% of newly developed Active Pharmaceutical Ingredients (APIs) exhibiting low solubility [1,2,3]. It is well known that solubility has a significant impact on drug efficacy [4]. Low solubility is more pronounced in orally administered drugs, as drugs with low solubility reduce the effectiveness of the active ingredients in the systemic circulation [5,6]. Therefore, improving the solubility of poorly soluble drugs is an important challenge in the development of orally administered pharmaceuticals [7,8].
Various techniques have been developed to enhance the solubility of poorly soluble drugs, including solid dispersion, particle size reduction, prodrugs, polymeric nanoparticles, lipid-based microspheres, inclusion complexes, salt formation, and lipid-based formulations [9,10]. Solid dispersion is defined as the dispersion of drugs within a polymer carrier matrix, prepared through methods such as melting, solvent evaporation, and solvent wetting [11]. In solid dispersions, drugs can be present in an amorphous form within the polymer carrier, and the drugs dispersed within the polymer carrier can possess enhanced solubility compared to their crystalline form due to their reduced particle size and increased surface area [12,13]. Among the various solubilization techniques available, solid dispersions have been widely used due to their advantage of not requiring special equipment and having a simpler preparation process compared to techniques that require the use of materials such as nanoparticles or nanoemulsions [14]. Furthermore, numerous poorly soluble drugs have been approved and marketed as pharmaceuticals using solid dispersion technology [15].
Olaparib (OLA), a poly ADP-ribose polymerase inhibitor (PARP inhibitor), is known to be therapeutically effective in treating cancers associated with impaired DNA repair capabilities, particularly those with deficiencies in the homologous recombination repair pathway [16,17]. The commercial product of OLA is Lynparza tablets, administered orally at a dose of two 150 mg tablets (300 mg) twice daily, with a total daily dose of 600 mg [18]. In spite of its many therapeutic benefits, OLA is classified as a Class IV drug according to the Biopharmaceutics Classification System (BCS) due to its low solubility of approximately 0.1 mg/mL in aqueous solutions and low permeability [19,20]. In previous studies, researchers have developed Hypromellose-based OLA solid dispersions, reflecting a solid dispersion system, to enhance the solubility and oral bioavailability of OLA [21]. HPMC has been utilized in various studies to enhance the solubility of poorly water soluble drugs [22,23]. HPMC was found to be very effective in stabilizing the amorphous form of OLA; however, it was less effective in significantly enhancing solubility. In this study, to address these problems, we incorporated surfactants, Tween 20 and Labrasol, known for their effectiveness in enhancing solubility, into the solid dispersion to improve the solubility and drug release of OLA [24,25]. Surfactants can increase the solubility of a drug by reducing the interfacial energy barrier between the drug and the aqueous solution. Furthermore, when the concentration of the surfactant exceeds the critical micelle concentration (CMC), it enhances the dissolution rate [26,27]. The solubility of OLA was investigated with various types of surfactants to select the type that could most significantly enhance the solubility of OLA. Subsequently, a quaternary solid dispersion (OLA-QSD) containing OLA, HPMC, a surfactant, and colloidal silica (used as a drying adjuvant in the spray-drying process) was prepared through spray drying [28]. The physicochemical properties of the prepared OLA-QSDs were evaluated using scanning electron microscopy (SEM), flowability, powder X-ray diffraction (PXRD), and fourier-transform infrared spectroscopy (FT-IR). The kinetic solubility and drug release through the dissolution of OLA-QSDs were evaluated in an aqueous solution. A concise overview of the research design is shown in Scheme 1.

2. Materials and Methods

2.1. Materials

OLA with a assay of 100.4% was purchased from Olon S.p.A. (Rodano, Italy). Caprylocaproyl macrogol-8 glycerides (abbreviated as Labrasol), Propylene glycol monocaprylate (abbreviated as Capryol 90), Propylene glycol monolaurate (abbreviated as Lauroglycol 90), Polyglyceryl-3 dioleate (abbreviated as Plurol Oleique CC 497), Propylene glycol monolaurate (type I) (abbreviated as Lauroglycol FCC), Linoleoyl polyoxyl-6 glycerides (abbreviated as Labrafil M 2125 CS), and Oleoyl polyoxyl-6 glycerides (abbreviated as Labrafil M 1944 CS) were supplied by Gattefosse (St. Priest, France). Polyethylene glycol (15)-hydroxystearate (abbreviated as Kolliphor HS15) and Polyethylene polypropylene glycol (abbreviated as Kollisolv P124) were acquired from BASF (Ludwigshafen, Germany). Polyoxyl-35 castor oil (abbreviated as Kolliphor EL) and Glyceryl tricaprylate (abbreviated as Tricaprylin) were obtained from Sigma Aldrich (St. Louis, MO, USA). Polyethylene glycol sorbitan monolaurate (abbreviated as Tween 20), Polyethylene glycol sorbitan monooleate (abbreviated as Tween 80), Sorbitan monooleate (abbreviated as Span 80), and Sorbitan monolaurate (abbreviated as Span 20) were sourced from Daejung Chemicals (Siheung, Republic of Korea). Polyglycerol polyricinoleate (abbreviated as PGPR) was acquired from MedChemExpress (Monmouth Junction, NJ, USA). Hypromellose 2910, P603 (abbreviated as HPMC) was kindly provided by Hanmi Pharmaceutical Co., Ltd. (Hwaseong, Republic of Korea). Colloidal silica was supplied by Boryung Pharmaceutical Co., Ltd. (Seoul, Republic of Korea). The deionized water used in the laboratory was produced using a distillation device. All other chemicals were of analytical grade.

2.2. HPLC Analysis Condition

The HPLC analysis of samples was conducted using an Agilent 1260 Infinity HPLC system (Agilent Technologies, Santa Clara, CA, USA) equipped with a UV–Vis detector (Agilent G1314 1260, Agilent Technologies, CA, USA). OLA was separated using a reversed-phase column (SunFire, 4.6 × 150 mm, 5 μm; Waters, Milford, MA, USA). The mobile phase was composed of a mixture of 2 g/L KH2PO4 buffer and acetonitrile (65:35, v/v), with the column temperature maintained at 30 °C [29]. The injection volume and flow rate were 10 μL and 1.0 mL/min, respectively, and the UV absorbance was set at 220 nm. Data acquisition and processing were carried out using Agilent OpenLAB CDS ChemStation LC software (Product Version: 2.18.18).

2.3. Surfactant Screening

The solubility of OLA in each surfactant was evaluated to screen the surfactants. To assess solubility, 10 mg of OLA drug powder was added to 1 mL of each 100% surfactant. The mixtures were vortexed for 10 min and then shaken at 100 rpm in a 37 °C water bath for 7 days. These samples were centrifuged at 13,500 rpm for 10 min, and the supernatant was obtained. It was then diluted 100-fold with the mobile phase mixture (A:B = 65:35, v/v) and filtered using a 0.45 μm syringe filter. The concentration of OLA in the filtered samples was analyzed using the HPLC conditions described in Section 2.2.

2.4. Preparation of OLA–QSD

Among the various methods employed for preparing solid dispersions, a spray dryer (Yamato ADL311SA; Yamato Scientific Co., Ltd., Tokyo, Japan) was used to prepare OLA–QSDs. According to previous studies, HPMC has been reported to effectively prevent the recrystallization of OLA and maintain a stable amorphous state [21]. Therefore, HPMC was selected as the polymer for OLA–QSDs, and Tween 20 and Labrasol, which exhibit high solubility of OLA as surfactants, were selected. HPMC and the surfactants were dissolved in a mixture of ethanol and deionized water (D.W.), after which OLA was dissolved. Thereafter, colloidal silica, which can improve the yield of the solid dispersion and enhance the dispersibility in the aqueous solution, was uniformly suspended in the solution before being spray-dried. Upon continuous stirring using a magnetic bar, the resulting dispersed solutions were delivered to the nozzle at a flow rate of 1.5 mL/min using a peristaltic pump and spray-dried at an inlet temperature of 85 °C and an outlet temperature of 50–55 °C, with an atomizing air pressure of 0.1 MPa. The obtained OLA-QSDs were further dried by storing them in a 60 °C dry oven for 30 min, after which the LOD (Loss on Drying) was confirmed to be below 1.0%. The samples were then stored in an polyethylene bag with silica gel. The detailed composition of the OLA–QSDs is shown in Table 1.

2.5. Scanning Electron Microscopy

The shape and surface morphology of the OLA drug powder and OLA–QSDs were examined using a scanning electron microscope (SEM) (Tescan-MIRA3; Tescan Korea, Seoul, Republic of Korea). Prior to analysis, all samples were mounted on stubs with double-sided adhesive tape and made electrically conductive through vacuum coating (7 × 10−3 mbar) with platinum (6 nm/min) using a Sputter Coater (K575X; EmiTech, Madrid, Spain) [30]. The coated samples were placed in a scanning electron microscope to observe their shape and surface morphology.

2.6. Flowability

The flowability of the OLA-QSDs was determined using the angle of repose, Carr’s index (%), and Hausner ratio. The angle of repose was measured after pouring the accurately weighed sample through a funnel. While keeping the bottom surface flat, the height and radius of the resultant conical pile were measured. The angle of repose was then calculated based on the inverse tangent (arctan) value of the pile using the following equation, where h and r refer to the height and radius, respectively:
θ   =   t a n − 1 h / r
A fixed amount (10 g) of each preparation was placed in a 100 mL graduated cylinder, and the bulk volume was measured. Subsequently, the preparations were tapped 1000 times, and the tapped volume was recorded. Each measurement was performed in triplicate [31]. The Carr’s index (CI) and Hausner ratio (HR) values were calculated as follows:
CI = 1 − ρ b u l k / ρ t a p p e d × 100 HR = ρ t a p p e d / ρ b u l k

2.7. Powder X-Ray Diffraction

To evaluate the crystallinity of the OLA drug powder and OLA–QSDs, powder X-ray diffraction (PXRD) (D/MAX-2500; Rigaku, Tokyo, Japan) was used for analysis. The analysis conditions were as follows: scanning 2θ range from 2° to 60° with an angular increment of 0.02°/s, Cu Kα radiation (λ = 1.54178 Å) at a voltage of 40 kV, and a scan speed of 10°/min [32].

2.8. Fourier-Transform Infrared Spectroscopy

To examine the infrared spectrum of OLA drug powder and OLA–QSDs, Fourier-transform infrared (FT-IR) spectroscopy analysis was performed using a Spectrum TwoTM (PerkinElmer, Waltham, MA, USA). The KBr pellet was prepared by mixing approximately 1 mg of the sample with 200 mg of KBr and using a pellet press. The samples were scanned across a spectral range from 4000 to 400 cm−1 [33].

2.9. Kinetic Solubility Test

To evaluate the kinetic solubility of the prepared OLA–QSDs, the OLA drug powder, and OLA–QSDs were added in amounts equivalent to 10 mg of OLA to 1 mL of solutions at pH 1.2 and pH 6.8, which represent physiological pH conditions [34]. The pH 1.2 solution was prepared using 0.1 M hydrochloric acid and sodium chloride, and the pH 6.8 solution was prepared by combining 0.2 M potassium dihydrogen phosphate solution with 0.2 M sodium hydroxide solution. Following vortexing of all samples for 10 min, the samples were shaken at 100 rpm in a water bath at 37 °C for 10 min, 30 min, 1 h, and 2 h. At each specified time point, samples were collected and subsequently centrifuged at 13,500 rpm for 10 min. The supernatant was then diluted 100-fold with the mobile phase mixture (A:B = 65:35, v/v) and filtered using a 0.45 μm syringe filter. The concentration of OLA in the filtered sample was analyzed using the HPLC conditions described in Section 2.2.

2.10. Dissolution Test

Dissolution tests were conducted to investigate the release of OLA–QSDs. To clearly evaluate the effect of the surfactant, a solid dispersion containing only HPMC and no surfactant was prepared, and dissolution tests were conducted together with the OLA–QSDs and OLA drug powder. During the dissolution test, a USP dissolution apparatus II (RCZ-6N; Pharmao Industries Co., Liaoyang, China) was utilized, with the temperature of the dissolution media adjusted to 37 ± 0.5 °C and the paddle speed set at 50 rpm. An amount corresponding to 150 mg of OLA was weighed and poured into the dissolution tester vessel, with the dissolution media consisting of 300 mL of pH 1.2 and pH 6.8 [35,36,37]. Samples (3 mL) were taken at predetermined time points (1, 2, 4, 6, 12, and 24 h), filtered through a 0.45 μm syringe filter, diluted 10-fold with the mobile phase mixture (A:B = 65:35, v/v), and analyzed using the HPLC conditions described in Section 2.2.

3. Results

3.1. Solubility of OLA in Surfactants

The solubility of a drug is a critical parameter that influences its bioavailability [38]. To select surfactants that can effectively enhance the solubility of OLA, the saturated solubility of OLA in each surfactant was evaluated. The solubility of OLA in D.W. showed a low solubility of approximately 0.1 mg/mL, consistent with the results of previous studies [39]. However, the solubility in surfactants differed depending on the type of surfactant, showing a solubility range of approximately 1 to 6 mg/mL (Figure 1).
Among the surfactants examined, Labrasol and Tween 20 showed the highest solubility, with a solubility of approximately 5.3 mg/mL. In particular, the surfactants Labrasol, Tween 20, Tween 80, Cremophor EL, and Kolliphor HS15, which are based on polyethylene glycol (PEG), exhibited high solubility (>3 mg/mL). These surfactants are known as the most commonly used non-ionic surfactants, based on ethylene oxide/polyoxyethylene, and are ethoxylated surfactants [40]. The multiple aromatic ring structures of OLA exhibit non-polar characteristics that interact with the hydrophobic tail of PEG, whereas the polar amide bonds and nitrogen and oxygen atoms in OLA interact with the ethoxy groups of PEG, both increasing the solubility of OLA (Figure 2) [41,42,43,44]. Based on the overall results of the solubility of OLA in various surfactants, Labrasol and Tween 20 were selected as surfactants that could effectively improve the solubility of OLA.

3.2. Shape and Surface Morphology

The spray-dried OLA-QSDs were observed to be in the form of a powder, exhibiting a color ranging from white to off-white (Figure 3). Additionally, visual observation showed that the particles appeared finer compared to the OLA drug powder.
After obtaining the dried OLA-QSDs, the physicochemical properties of the prepared OLA-QSDs were evaluated. SEM images of the OLA drug powder and solids in the composition of OLA-QSD, namely HPMC and colloidal silica, are shown in Figure 4. Pure OLA drug powder exhibited an irregularly shaped polyhedral crystalline morphology, with particle sizes of approximately 5 μm to 20 μm. HPMC appeared as large, elongated aggregates of fiber-like particles, with a size of approximately 25 μm to 200 μm [45]. Colloidal silica was found to have a spherical shape with a homogeneous size distribution and shallow porosity on its surface [46].
OLA-QSDs exhibited significant changes in particle shape and surface morphology (Figure 5). In the OLA-QSDs, the crystalline morphology observed in the OLA drug powder was not exhibited, and the particles were spherical in shape. These results indicate that the OLA drug powder was transformed into spherical particles through spray drying. However, there was a difference in particle shape between F1 to F4. The particle size of F1 and F2 was over 5 μm; in comparison, F3 and F4 possessed smaller particle sizes (less than 5 μm). Additionally, the particles observed in F1 and F2 exhibited a rough, uneven spherical shape, unlike the smoother particles seen in F3 and F4. These results suggest that the amount of polymer can affect the particle size or surface morphology of OLA-QSDs.

3.3. Evaluation of Flow Properties

To assess the flow properties of the OLA drug powder and OLA-QSDs, the angle of repose (Figure 6A), Carr’s index (Figure 6B), and Hausner ratio (Figure 6C) were evaluated. The flow properties of powders are important factors in solid oral dosage forms and can be determined through parameters such as the angle of repose, Hausner ratio, and Carr’s index [47,48]. Higher values of these parameters indicate relatively lower flow properties [49]. Our results indicated that OLA drug powder had the highest angle of repose at 53 degrees, the highest CI at 37%, and the highest HR at 1.6 compared to the OLA-QSDs. In contrast, OLA-QSDs showed a lower angle of repose, ranging from approximately 38 to 43 degrees, a CI ranging from 18 to 23%, and an HR ranging from 1.2 to 1.3 compared to the OLA drug powder, indicating improved flow properties. These results could be attributed to the irregularly shaped polyhedral crystalline morphology of the OLA drug powder possibly leading to increased frictional forces that hinder flow, resulting in poor flowability; in comparison, the spray-dried OLA-QSDs possessed particles that were spherical and of consistent size, which improved flowability [50]. Additionally, the presence of colloidal silica particles adsorbed onto the host powder particles smooths the surface, reducing friction and mechanical interlocking between particles during flow [51]. As a result, the OLA-QSDs exhibited improved flow properties.

3.4. Crystallinity State and FT-IR Analysis of Molecular State Alterations

The crystallinity of the prepared OLA-QSDs was confirmed using PXRD (Figure 7A). In OLA drug powder, distinct high-intensity peaks were observed depending on the dif-fraction angle, indicating that OLA drug powder is crystalline. In contrast, the high-intensity peaks observed in the OLA drug powder disappeared in F3 and F4, indicating an amorphous state [52]. Therefore, it can be concluded that the crystalline form of the drug was transformed into amorphous during the preparation of the solid dispersion through spray drying. However, in F1 and F2, unlike F3 and F4, the characteristic peaks of OLA (Red arrow) were observed at lower intensities. Considering the rough surface observed in the SEM images of F1 and F2, it could be determined that these samples were not completely amorphous. Based on these results, it was demonstrated that an increased amount of polymer can contribute to the formation of amorphous particles.
The results of a number of studies demonstrate that changes in molecular structure, in addition to the form of the drug crystallinity, prevent the drug from penetrating the gastrointestinal membrane, leading to a decrease in oral bioavailability [53,54]. Therefore, changes in the molecular state of the drug were evaluated using FT-IR by identifying molecular stretching vibrations or peak expansions (Figure 7B). In FT–IR spectra, the OLA drug powder presented characteristic stretches at 3400 cm−1, 3000–3165 cm−1, and 1611–1655 cm−1, indicating the presence of amide groups (N-H), amine groups (N-H), and carbonyl groups (C=O), respectively. Moreover, peaks corresponding to aromatic ring (C=C, C-H) stretch bands were observed at 1611–1655 cm−1 and 750–812 cm−1 in the OLA drug powder [55,56]. Specific signals of the OLA drug powder were observed in the OLA-QSDs, suggesting that there were no molecular interactions between the OLA and the excipients. The FT-IR results were consistent with reports in the literature that the spray-drying process scarcely induces molecular interactions between the drug and excipients [57]. Based on our PXRD and FT-IR results, it was observed that all OLA-QSDs were in an amorphous state with no molecular changes of OLA in the solid dispersions.

3.5. Kinetic Solubility of OLA-QSDs

The kinetic solubility of the prepared OLA-QSDs over time at pH 1.2 and pH 6.8 was investigated (Figure 8). All samples exhibited pH-independent solubility, with the OLA drug powder showing a solubility of approximately 150 µg/mL, which did not increase or decrease over time. F1 and F2 exhibited a solubility of approximately 200 µg/mL, which was not significantly different from that of the OLA drug powder. Unlike F1 and F2, F3 and F4 showed significantly increased solubility compared to the OLA drug powder, with F3 exhibiting a maximum solubility of approximately 1800 µg/mL and F4 exhibiting a maximum solubility of approximately 500 µg/mL. The significant difference in solubility between F1 and F2 and F3 and F4 was attributed to the difference in crystallization inhibition efficacy due to the varying amounts of polymer in the supersaturated solutions (approximately 10,000 µg/mL), with F1 and F2 containing 150 mg of HPMC and F3 and F4 containing 300 mg of HPMC [58]. Furthermore, it was observed that the amount of HPMC not only affected the kinetic solubility but was also related to achieving a completely amorphous state, as evidenced by SEM and PXRD observations. Therefore, it was demonstrated that the solubility of F3 and F4, which contain a higher amount of HPMC and are completely amorphous, is higher than that of F1 and F2, which retain a small amount of crystalline form. However, the solubility of F3 and F4 rapidly decreased over time, which is attributed to precipitation from the amorphous to the crystalline state under supersaturated conditions [59]. The difference in solubility between F3 and F4 could be attributed to a variety of reasons, including different types of surfactants having different degrees of drug-polymer miscibility and different abilities to increase the equilibrium solubility of the drug [60]. The kinetic solubility results for OLA revealed that Tween 20 was more effective than Labrasol at enhancing the solubility of OLA.

3.6. Drug Release of OLA-QSDs

The dissolution test for OLA-QSDs was performed in pH 1.2 and pH 6.8 solutions. To compare the effects of surfactants on the enhancement of the dissolution rate, dissolution tests were also conducted using S1 and S2, which did not contain Tween 20 or Labrasol. The dissolution results for S1, F1, and F2, which possess an OLA drug powder-to-HPMC ratio of 1:1 (w/w), are shown in Figure 9. Regardless of the pH, the OLA drug powder exhibited approximately 20% drug release. In the case of S1, which did not contain any surfactants, drug release at the end of 24 h was recorded at 34% at pH 1.2 and 37% at pH 6.8, with the release rate gradually increasing over time. In contrast, F1 and F2, which contained surfactants, exhibited higher drug release compared to S1. These results can be attributed to the fact that surfactants providing surface activity are effective in preventing the formation of hydrophobic barriers upon contact with aqueous solutions or the aggregation of recrystallized drug particles after dispersion [61]. For F1, a maximum drug release rate of up to 95% was achieved regardless of pH, while F2 showed a drug release rate of 70%. However, unlike F2, which did not show a decrease in drug release, F1 began to exhibit a decrease in drug release starting at 12 h, decreasing to 80% at pH 1.2 and 68% at pH 6.8 by 24 h. These results were consistent with the kinetic solubility findings, showing that F1, using Tween 20, exhibited high solubility when dispersed in aqueous solution. However, it was observed that F1 recrystallized more rapidly in the supersaturated solution compared to F2, which contained Labrasol, resulting in a decrease in the release rate.
The dissolution results for S2, F3, and F4, with an OLA drug powder-to-HPMC ratio of 1:2 (w/w), are shown in Figure 10. Unlike S1, S2 demonstrated an improvement in the drug release rate, increasing from approximately 30% to 80% as the amount of HPMC was increased. These results were consistent with the kinetic solubility results, which showed differences in solubility depending on the amount of polymer present. In the case of F3 and F4, which contain surfactants, the drug release rate increased to approximately 97% regardless of pH, demonstrating a higher dissolution rate compared to S2, which does not contain surfactants. The enhanced dissolution of OLA in solid dispersions can be attributed to several factors, including the lack of crystallinity, reduced particle size, decreased interfacial tension between the hydrophobic drug and the dissolution medium, increased wettability, and the effective surface adsorption of the drug onto the polymeric carrier and surfactants [62]. Considering the overall dissolution results, it was demonstrated that the inclusion of surfactants in OLA-QSDs can enhance the release of OLA more effectively than when surfactants are not included. These results suggest that OLA-QSDs based on HPMC and Tween 20 or Labrasol can exhibit improved bioavailability by enhancing the low solubility of OLA.

4. Conclusions

The results of this study demonstrate the enhancement of the solubility of OLA, a first-in-class PARP inhibitor, through the preparation of solid dispersions via spray drying to improve its low-solubility characteristics. The solubility of OLA was further increased by preparing a solid dispersion with the addition of a surfactant coupled with the polymer. To select an effective surfactant, we evaluated the solubility of OLA in a variety of surfactants. As a result, OLA, which has a low solubility of approximately 0.1 mg/mL in D.W., exhibited a solubility of over 5 mg/mL in Labrasol and Tween 20. These results indicated that Labrasol and Tween 20 could contribute to enhancing the solubility of OLA. Subsequently, quaternary solid dispersions containing OLA, HPMC, a surfactant, and colloidal silica were prepared, and it was verified that they transformed into an amorphous state. Additionally, OLA-QSDs showed improved flow properties compared to the OLA drug powder through spray drying, and there were no intermolecular interactions within the solid dispersion. The amount of polymer used and the type of surfactant in OLA-QSDs were key parameters in enhancing their solubility. As the amount of polymer increased, smaller particles and completely amorphous particles were formed, which contributed to the enhanced solubility of OLA. Furthermore, the solid dispersions containing surfactants exhibited a higher dissolution rate compared to those with no surfactants, and Tween 20 was more effective than Labrasol in enhancing the solubility of OLA. In conclusion, this formulation, by incorporating surfactants and colloidal silica to prepare quaternary solid dispersions, can potentially lead to improved oral absorption through enhanced solubility and suggests the feasibility of large-scale production via spray-drying technology.

Author Contributions

Conceptualization, T.-H.Y.; formal analysis, T.-H.Y. and J.-G.L.; writing—original draft preparation, T.-H.Y., K.-H.B. and J.-H.C.; supervision, J.-H.C. and K.-S.K.; project administration, K.-S.K.; funding acquisition, K.-S.K. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

Data are available upon request due to restrictions, e.g., privacy or ethical restrictions.

Conflicts of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

References

  1. Gigliobianco, M.R.; Casadidio, C.; Censi, R.; Di Martino, P. Nanocrystals of poorly soluble drugs: Drug bioavailability and physicochemical stability. Pharmaceutics 2018, 10, 134. [Google Scholar] [CrossRef]
  2. Tuomela, A.; Hirvonen, J.; Peltonen, L. Stabilizing agents for drug nanocrystals: Effect on bioavailability. Pharmaceutics 2016, 8, 16. [Google Scholar] [CrossRef] [PubMed]
  3. Merisko-Liversidge, E.; Liversidge, G.G. Nanosizing for oral and parenteral drug delivery: A perspective on formulating poorly-water soluble compounds using wet media milling technology. Adv. Drug Deliv. Rev. 2011, 63, 427–440. [Google Scholar] [CrossRef] [PubMed]
  4. Daugherty, A.L.; Mrsny, R.J. Transcellular uptake mechanisms of the intestinal epithelial barrier Part one. Pharm. Sci. Technol. Today 1999, 2, 144–151. [Google Scholar] [CrossRef] [PubMed]
  5. Ainurofiq, A.; Putro, D.S.; Ramadhani, D.A.; Putra, G.M.; Santo, L.D.C.D.E. A review on solubility enhancement methods for poorly water-soluble drugs. J. Rep. Pharm. Sci. 2021, 10, 137–147. [Google Scholar] [CrossRef]
  6. Ghosh, P.; Rasmuson, A.; Hudson, S.P. Impact of additives on drug particles during liquid antisolvent crystallization and subsequent freeze-drying. Org. Process Res. Dev. 2023, 27, 2020–2034. [Google Scholar] [CrossRef] [PubMed]
  7. Fong, S.Y.K.; Ibisogly, A.; Bauer-Brandl, A. Solubility enhancement of BCS Class II drug by solid phospholipid dispersions: Spray drying versus freeze-drying. Int. J. Pharm. 2015, 496, 382–391. [Google Scholar] [CrossRef]
  8. Savjani, K.T.; Gajjar, A.K.; Savjani, J.K. Drug solubility: Importance and enhancement techniques. Int. Sch. Res. Not. 2012, 2012, 195727. [Google Scholar] [CrossRef]
  9. Lee, S.-M.; Lee, J.-G.; Yun, T.-H.; Cho, J.-H.; Kim, K.-S. Enhanced Stability and Improved Oral Absorption of Enzalutamide with Self-Nanoemulsifying Drug Delivery System. Int. J. Mol. Sci. 2024, 25, 1197. [Google Scholar] [CrossRef] [PubMed]
  10. Alam, M.A.; Ali, R.; Al-Jenoobi, F.I.; Al-Mohizea, A.M. Solid dispersions: A strategy for poorly aqueous soluble drugs and technology updates. Expert Opin. Drug Deliv. 2012, 9, 1419–1440. [Google Scholar] [CrossRef] [PubMed]
  11. Huang, Y.; Dai, W.-G. Fundamental aspects of solid dispersion technology for poorly soluble drugs. Acta Pharm. Sin. B 2014, 4, 18–25. [Google Scholar] [CrossRef] [PubMed]
  12. Oh, D.H.; Park, Y.-J.; Kang, J.H.; Yong, C.S.; Choi, H.-G. Physicochemical characterization and in vivo evaluation of flurbiprofen-loaded solid dispersion without crystalline change. Drug Deliv. 2011, 18, 46–53. [Google Scholar] [CrossRef] [PubMed]
  13. Craig, D.Q. The mechanisms of drug release from solid dispersions in water-soluble polymers. Int. J. Pharm. 2002, 231, 131–144. [Google Scholar] [CrossRef] [PubMed]
  14. Okada, K.; Ono, T.; Hayashi, Y.; Kumada, S.; Onuki, Y. Use of Time-Domain NMR for 1H T1 Relaxation Measurement and Fitting Analysis in Homogeneity Evaluation of Amorphous Solid Dispersion. J. Pharm. Sci. 2024, 113, 680–687. [Google Scholar] [CrossRef]
  15. Zhao, P.; Han, W.; Shu, Y.; Li, M.; Sun, Y.; Sui, X.; Liu, B.; Tian, B.; Liu, Y.; Fu, Q. Liquid–liquid phase separation drug aggregate: Merit for oral delivery of amorphous solid dispersions. J. Control. Release 2023, 353, 42–50. [Google Scholar] [CrossRef] [PubMed]
  16. Chatterjee, I.; Roy, D.; Panda, G. A scalable and eco-friendly total synthesis of poly (ADP-ribose) polymerase inhibitor Olaparib. Green Chem. 2023, 25, 9097–9102. [Google Scholar] [CrossRef]
  17. Freire Boullosa, L.; Van Loenhout, J.; Flieswasser, T.; Hermans, C.; Merlin, C.; Lau, H.W.; Marcq, E.; Verschuuren, M.; De Vos, W.H.; Lardon, F. Auranofin synergizes with the PARP inhibitor olaparib to induce ROS-mediated cell death in mutant p53 cancers. Antioxidants 2023, 12, 667. [Google Scholar] [CrossRef] [PubMed]
  18. Heo, Y.-A.; Dhillon, S. Olaparib tablet: A review in ovarian cancer maintenance therapy. Target. Oncol. 2018, 13, 801–808. [Google Scholar] [CrossRef]
  19. Hirlekar, B.U.; Nuthi, A.; Singh, K.D.; Murty, U.S.; Dixit, V.A. An overview of compound properties, multiparameter optimization, and computational drug design methods for PARP-1 inhibitor drugs. Eur. J. Med. Chem. 2023, 252, 115300. [Google Scholar] [CrossRef] [PubMed]
  20. Orleni, M.; Canil, G.; Posocco, B.; Gagno, S.; Toffoli, G. Bioanalytical Methods for Poly (ADP-Ribose) Polymerase Inhibitor Quantification: A Review for Therapeutic Drug Monitoring. Ther. Drug Monit. 2023, 45, 306–317. [Google Scholar] [CrossRef]
  21. Yun, T.; Lee, S.; Yun, S.; Cho, D.; Bang, K.; Kim, K. Investigation of Stabilized Amorphous Solid Dispersions to Improve Oral Olaparib Absorption. Pharmaceutics 2024, 16, 958. [Google Scholar] [CrossRef]
  22. Fan, N.; Ma, P.; Wang, X.; Li, C.; Zhang, X.; Zhang, K.; Li, J.; He, Z. Storage stability and solubilization ability of HPMC in curcumin amorphous solid dispersions formulated by Eudragit E100. Carbohydr. Polym. 2018, 199, 492–498. [Google Scholar] [CrossRef] [PubMed]
  23. Tekade, A.R.; Yadav, J.N. A review on solid dispersion and carriers used therein for solubility enhancement of poorly water soluble drugs. Adv. Pharm. Bull. 2020, 10, 359–369. [Google Scholar] [CrossRef]
  24. Akbari, J.; Saeedi, M.; Morteza-Semnani, K.; Kelidari, H.R.; Moghanlou, F.S.; Zareh, G.; Rostamkalaei, S. The effect of Tween 20, 60, and 80 on dissolution behavior of sprionolactone in solid dispersions prepared by PEG 6000. Adv. Pharm. Bull. 2015, 5, 435–441. [Google Scholar] [CrossRef]
  25. Soliman, M.; Khan, M. Preparation and in vitro characterization of a semi-solid dispersion of flurbiprofen with Gelucire 44/14 and Labrasol. Die Pharm.-Int. J. Pharm. Sci. 2005, 60, 288–293. [Google Scholar]
  26. Gibaldi, M.; Feldman, S.; Wynn, R.; Weiner, N. Dissolution rates in surfactant solutions under stirred and static conditions. J. Pharm. Sci. 1968, 57, 787–791. [Google Scholar] [CrossRef] [PubMed]
  27. Singh, P.; Desai, S.; Flanagan, D.; Simonelli, A.; Higuchi, W. Mechanistic study of the influence of micelle solubilization and hydrodynamic factors on the dissolution rate of solid drugs. J. Pharm. Sci. 1968, 57, 959–965. [Google Scholar] [CrossRef] [PubMed]
  28. Tewa-Tagne, P.; Briançon, S.; Fessi, H. Spray-dried microparticles containing polymeric nanocapsules: Formulation aspects, liquid phase interactions and particles characteristics. Int. J. Pharm. 2006, 325, 63–74. [Google Scholar] [CrossRef]
  29. Yasu, T.; Nishijima, R.; Ikuta, R.; Shirota, M.; Iwase, H. Development of a simple high-performance liquid chromatography-ultraviolet detection method for olaparib in patients with ovarian cancer. Drug Discov. Ther. 2023, 17, 428–433. [Google Scholar] [CrossRef] [PubMed]
  30. Choi, M.-J.; Woo, M.R.; Choi, H.-G.; Jin, S.G. Effects of polymers on the drug solubility and dissolution enhancement of poorly water-soluble rivaroxaban. Int. J. Mol. Sci. 2022, 23, 9491. [Google Scholar] [CrossRef] [PubMed]
  31. Kim, J.S.; ud Din, F.; Choi, Y.J.; Woo, M.R.; Cheon, S.; Ji, S.H.; Park, S.; Kim, J.O.; Youn, Y.S.; Lim, S.-J. Hydroxypropyl-β-cyclodextrin-based solid dispersed granules: A prospective alternative to conventional solid dispersion. Int. J. Pharm. 2022, 628, 122286. [Google Scholar]
  32. Choi, M.-J.; Woo, M.R.; Baek, K.; Park, J.H.; Joung, S.; Choi, Y.S.; Choi, H.-G.; Jin, S.G. Enhanced oral bioavailability of Rivaroxaban-Loaded microspheres by optimizing the polymer and surfactant based on molecular interaction mechanisms. Mol. Pharm. 2023, 20, 4153–4164. [Google Scholar] [CrossRef] [PubMed]
  33. Park, J.-B.; Kang, C.-Y.; Kang, W.-S.; Choi, H.-G.; Han, H.-K.; Lee, B.-J. New investigation of distribution imaging and content uniformity of very low dose drugs using hot-melt extrusion method. Int. J. Pharm. 2013, 458, 245–253. [Google Scholar] [CrossRef] [PubMed]
  34. Araujo-Fernandez, A.S.; Uribe-Villarreal, J.C.; Perez-Chauca, E.; Alva-Plasencia, P.M.; Caballero-Aquiño, O.E.; Ganoza-Yupanqui, M.L. Validation of a UV spectrophotometric method to quantify losartan potassium in tablets from the dissolution test at pH 1.2, 4.5 and 6.8. J. Pharm. Pharmacogn. Res. 2022, 10, 310–317. [Google Scholar] [CrossRef]
  35. Nepal, P.R.; Han, H.-K.; Choi, H.-K. Enhancement of solubility and dissolution of Coenzyme Q10 using solid dispersion formulation. Int. J. Pharm. 2010, 383, 147–153. [Google Scholar] [CrossRef]
  36. Ha, E.-S.; Baek, I.-h.; Cho, W.; Hwang, S.-J.; Kim, M.-S. Preparation and evaluation of solid dispersion of atorvastatin calcium with Soluplus® by spray drying technique. Chem. Pharm. Bull. 2014, 62, 545–551. [Google Scholar] [CrossRef] [PubMed]
  37. Duret, C.; Wauthoz, N.; Sebti, T.; Vanderbist, F.; Amighi, K. Solid dispersions of itraconazole for inhalation with enhanced dissolution, solubility and dispersion properties. Int. J. Pharm. 2012, 428, 103–113. [Google Scholar] [CrossRef]
  38. Müller, C.E. Prodrug approaches for enhancing the bioavailability of drugs with low solubility. Chem. Biodivers. 2009, 6, 2071–2083. [Google Scholar] [CrossRef] [PubMed]
  39. Kim, Y.-H.; Kim, S.-B.; Choi, S.-H.; Nguyen, T.-T.-L.; Ahn, S.-H.; Moon, K.-S.; Cho, K.-H.; Sim, T.-Y.; Heo, E.-J.; Kim, S.T. Development and Evaluation of Self-Microemulsifying Drug Delivery System for Improving Oral Absorption of Poorly Water-Soluble Olaparib. Pharmaceutics 2023, 15, 1669. [Google Scholar] [CrossRef]
  40. Koehl, N.J.; Holm, R.; Kuentz, M.; Jannin, V.; Griffin, B.T. Exploring the impact of surfactant type and digestion: Highly digestible surfactants improve oral bioavailability of nilotinib. Mol. Pharm. 2020, 17, 3202–3213. [Google Scholar] [CrossRef] [PubMed]
  41. Pan, C.; Chen, L.; Zhang, X.; Zhang, D.; Song, Q.; Peng, J.; Li, Q. Molecular insight into the π-stacking interactions of human ovarian cancer PARP-1 with its small-molecule inhibitors and rational design of aromatic amino acid-rich peptides to target PARP-1 based on the π-stacking network. J. Chin. Chem. Soc. 2022, 69, 775–785. [Google Scholar] [CrossRef]
  42. Foumthuim, C.J.D.; Carrer, M.; Houvet, M.; Škrbić, T.; Graziano, G.; Giacometti, A. Can the roles of polar and non-polar moieties be reversed in non-polar solvents? Phys. Chem. Chem. Phys. 2020, 22, 25848–25858. [Google Scholar] [CrossRef]
  43. Dey, J.; Ghosh, R.; Das Mahapatra, R. Self-assembly of unconventional low-molecular-mass amphiphiles containing a PEG chain. Langmuir 2018, 35, 848–861. [Google Scholar] [CrossRef] [PubMed]
  44. Crescenzi, C.; Di Corcia, A.; Marcomini, A.; Samperi, R. Detection of poly (ethylene glycols) and related acidic forms in environmental waters by liquid chromatography/electrospray/mass spectrometry. Environ. Sci. Technol. 1997, 31, 2679–2685. [Google Scholar] [CrossRef]
  45. Allenspach, C.; Timmins, P.; Sharif, S.; Minko, T. Characterization of a novel hydroxypropyl methylcellulose (HPMC) direct compression grade excipient for pharmaceutical tablets. Int. J. Pharm. 2020, 583, 119343. [Google Scholar] [CrossRef]
  46. Lee, D.R.; Kim, Y.H.; Park, K.W.; Ho, M.J.; Jung, H.J.; Cho, H.R.; Park, J.S.; Choi, Y.S.; Yeom, D.W.; Choi, Y.W. Fujicalin®-based solid supersaturable self-emulsifying drug delivery system (S-SEDDS) of tacrolimus for enhanced dissolution rate and oral absorption. J. Pharm. Investig. 2015, 45, 651–658. [Google Scholar] [CrossRef]
  47. Bhattachar, S.N.; Hedden, D.B.; Olsofsky, A.M.; Qu, X.; Hsieh, W.-Y.; Canter, K.G. Evaluation of the vibratory feeder method for assessment of powder flow properties. Int. J. Pharm. 2004, 269, 385–392. [Google Scholar] [CrossRef]
  48. Kim, D.S.; Kim, J.S.; Lim, S.-J.; Kim, J.O.; Yong, C.S.; Choi, H.-G.; Jin, S.G. Comparison of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol-loaded self-emulsifying granule and solid self-nanoemulsifying drug delivery system: Powder property, dissolution and oral bioavailability. Pharmaceutics 2019, 11, 415. [Google Scholar] [CrossRef]
  49. Eroğlu, İ.; Gökçe, E.H.; Tsapis, N.; Tanrıverdi, S.T.; Gökçe, G.; Fattal, E.; Özer, Ö. Evaluation of characteristics and in vitro antioxidant properties of RSV loaded hyaluronic acid–DPPC microparticles as a wound healing system. Colloids Surf. B Biointerfaces 2015, 126, 50–57. [Google Scholar] [CrossRef] [PubMed]
  50. Ramavath, P.; Swathi, M.; Suresh, M.B.; Johnson, R. Flow properties of spray dried alumina granules using powder flow analysis technique. Adv. Powder Technol. 2013, 24, 667–673. [Google Scholar] [CrossRef]
  51. Badawy, M.A.; Kamel, A.O.; Sammour, O.A. Use of biorelevant media for assessment of a poorly soluble weakly basic drug in the form of liquisolid compacts: In vitro and in vivo study. Drug Deliv. 2016, 23, 808–817. [Google Scholar] [CrossRef]
  52. Liu, P.; Zhou, J.-Y.; Chang, J.-H.; Liu, X.-G.; Xue, H.-F.; Wang, R.-X.; Li, Z.-S.; Li, C.-S.; Wang, J.; Liu, C.-Z. Soluplus-mediated diosgenin amorphous solid dispersion with high solubility and high stability: Development, characterization and oral bioavailability. Drug Des. Dev. Ther. 2020, 14, 2959–2975. [Google Scholar] [CrossRef]
  53. Kim, J.S.; Choi, Y.J.; Woo, M.R.; Cheon, S.; Ji, S.H.; Im, D.; ud Din, F.; Kim, J.O.; Youn, Y.S.; Oh, K.T. New potential application of hydroxypropyl-β-cyclodextrin in solid self-nanoemulsifying drug delivery system and solid dispersion. Carbohydr. Polym. 2021, 271, 118433. [Google Scholar] [CrossRef]
  54. Veber, D.F.; Johnson, S.R.; Cheng, H.-Y.; Smith, B.R.; Ward, K.W.; Kopple, K.D. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 2002, 45, 2615–2623. [Google Scholar] [CrossRef]
  55. Anwer, M.K.; Ali, E.A.; Iqbal, M.; Ahmed, M.M.; Aldawsari, M.F.; Saqr, A.A.; Alalaiwe, A.; Soliman, G.A. Development of chitosan-coated PLGA-based nanoparticles for improved oral olaparib delivery: In vitro characterization, and in vivo pharmacokinetic studies. Processes 2022, 10, 1329. [Google Scholar] [CrossRef]
  56. Alali, A.S.; Kalam, M.A.; Ahmed, M.M.; Aboudzadeh, M.A.; Alhudaithi, S.S.; Anwer, M.K.; Fatima, F.; Iqbal, M. Nanocrystallization improves the solubilization and cytotoxic effect of a poly (Adp-ribose)-polymerase-i inhibitor. Polymers 2022, 14, 4827. [Google Scholar] [CrossRef]
  57. Kim, J.S.; Cheon, S.; Woo, M.R.; Woo, S.; Chung, J.-E.; Youn, Y.S.; Oh, K.T.; Lim, S.-J.; Ku, S.K.; Nguyen, B.L. Electrostatic spraying for fine-tuning particle dimensions to enhance oral bioavailability of poorly water-soluble drugs. Asian J. Pharm. Sci. 2024, 19, 100953. [Google Scholar] [CrossRef] [PubMed]
  58. Konno, H.; Handa, T.; Alonzo, D.E.; Taylor, L.S. Effect of polymer type on the dissolution profile of amorphous solid dispersions containing felodipine. Eur. J. Pharm. Biopharm. 2008, 70, 493–499. [Google Scholar] [CrossRef] [PubMed]
  59. Han, Y.R.; Lee, P.I. Effect of extent of supersaturation on the evolution of kinetic solubility profiles. Mol. Pharm. 2017, 14, 206–220. [Google Scholar] [CrossRef]
  60. Guan, Q.; Ma, Q.; Zhao, Y.; Jiang, X.; Zhang, H.; Liu, M.; Wang, Z.; Han, J. Cellulose derivatives as effective recrystallization inhibitor for ternary ritonavir solid dispersions: In vitro-in vivo evaluation. Carbohydr. Polym. 2021, 273, 118562. [Google Scholar] [CrossRef]
  61. Pouton, C.W. Formulation of poorly water-soluble drugs for oral administration: Physicochemical and physiological issues and the lipid formulation classification system. Eur. J. Pharm. Sci. 2006, 29, 278–287. [Google Scholar] [CrossRef] [PubMed]
  62. Dave, R.H.; Patel, A.D.; Donahue, E.; Patel, H.H. To evaluate the effect of addition of an anionic surfactant on solid dispersion using model drug indomethacin. Drug Dev. Ind. Pharm. 2012, 38, 930–939. [Google Scholar] [CrossRef]
Solids 06 00001 sch001
Scheme 1. Overview of the research design in this study.
Scheme 1. Overview of the research design in this study.
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Figure 1. Saturation solubility of OLA in various surfactants.
Figure 1. Saturation solubility of OLA in various surfactants.
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Figure 2. Molecular structures of (A) OLA, (B) Tween 20, and (C) Labrasol.
Figure 2. Molecular structures of (A) OLA, (B) Tween 20, and (C) Labrasol.
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Figure 3. The appearance of the OLA drug powder and OLA-QSDs.
Figure 3. The appearance of the OLA drug powder and OLA-QSDs.
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Figure 4. SEM images of the OLA drug powder (×10,000), HPMC (×1000), and colloidal silica (×2000).
Figure 4. SEM images of the OLA drug powder (×10,000), HPMC (×1000), and colloidal silica (×2000).
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Figure 5. SEM images of the OLA-QSDs (×10,000).
Figure 5. SEM images of the OLA-QSDs (×10,000).
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Figure 6. (A) The angle of repose, (B) Carr’s compressibility index, and (C) the Hausner ratio of the OLA drug powder and OLA-QSDs.
Figure 6. (A) The angle of repose, (B) Carr’s compressibility index, and (C) the Hausner ratio of the OLA drug powder and OLA-QSDs.
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Figure 7. (A) FT-IR spectra and (B) Powder X-ray diffractogram of the OLA drug powder and OLA-QSDs.
Figure 7. (A) FT-IR spectra and (B) Powder X-ray diffractogram of the OLA drug powder and OLA-QSDs.
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Figure 8. Kinetic solubility of the OLA drug powder and OLA-QSDs at (A) pH 1.2 and (B) pH 6.8.
Figure 8. Kinetic solubility of the OLA drug powder and OLA-QSDs at (A) pH 1.2 and (B) pH 6.8.
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Figure 9. The dissolution profiles of the OLA drug powder, S1, and OLA-QSDs (F1~F2) at (A) pH 1.2 and (B) pH 6.8.
Figure 9. The dissolution profiles of the OLA drug powder, S1, and OLA-QSDs (F1~F2) at (A) pH 1.2 and (B) pH 6.8.
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Figure 10. The dissolution profiles of the OLA drug powder, S2, and OLA-QSDs (F3~F4) at (A) pH 1.2 and (B) pH 6.8.
Figure 10. The dissolution profiles of the OLA drug powder, S2, and OLA-QSDs (F3~F4) at (A) pH 1.2 and (B) pH 6.8.
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Table 1. Composition of OLA-QSD formulations.
Table 1. Composition of OLA-QSD formulations.
Formulation (mg)F1F2F3F4S1S2
OLA150150150150150150
HPMC 2910 P603150150300300150300
Tween 2075-75---
Labrasol-75-75--
Colloidal silica757575757575
(Ethanol)(5500)(5500)(5500)(5500)(5500)(5500)
(D.W.)(2000)(2000)(2000)(2000)(2000)(2000)
Total450450600600375525
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Yun, T.-H.; Lee, J.-G.; Bang, K.-H.; Cho, J.-H.; Kim, K.-S. A Quaternary Solid Dispersion System for Improving the Solubility of Olaparib. Solids 2025, 6, 1. https://doi.org/10.3390/solids6010001

AMA Style

Yun T-H, Lee J-G, Bang K-H, Cho J-H, Kim K-S. A Quaternary Solid Dispersion System for Improving the Solubility of Olaparib. Solids. 2025; 6(1):1. https://doi.org/10.3390/solids6010001

Chicago/Turabian Style

Yun, Tae-Han, Jeong-Gyun Lee, Kyu-Ho Bang, Jung-Hyun Cho, and Kyeong-Soo Kim. 2025. "A Quaternary Solid Dispersion System for Improving the Solubility of Olaparib" Solids 6, no. 1: 1. https://doi.org/10.3390/solids6010001

APA Style

Yun, T.-H., Lee, J.-G., Bang, K.-H., Cho, J.-H., & Kim, K.-S. (2025). A Quaternary Solid Dispersion System for Improving the Solubility of Olaparib. Solids, 6(1), 1. https://doi.org/10.3390/solids6010001

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