Intrinsic Dissolution Rate Research Articles

PARTIAL AMORPHIZATION OF POORLY-SOLUBLE SIMVASTATIN USP USING MEDIA MILLING IN SYNERGISM WITH SPRAY-DRYING

Objective: The objective of the current study was to explore top down methods of size reduction like high speed homogenisation and media milling in synergism with spray drying in amorphization and solubility enhancement of BCS Class II antilipidemic drug Simvastatin USP.
 Methods: Spray-dried micronized simvastatin USP was formulated by homogenisation and media milling of drug suspension in optimized stabilizer solution. Stabilizer combination, duration of homogenisation and ball milling and drug: stabilizer ratio was optimized. The obtained dispersion was transformed into solid powder using spray drying. The obtained Spray-dried micronized Simvastatin USP was evaluated for visual morphology, Infrared spectroscopy, Differential scanning calorimetry, in vitro drug release studies, X-Ray diffractometry, Scanning electron microscopy, contact angle measurement, solubility studies, dispersibility studies and intrinsic dissolution rate testing.
 Results: Spray-dried micronized simvastatin USP was found to show amorphization of crystalline Simvastatin USP as confirmed by the absence of drug peak in Differential scanning calorimetry and lowered signal intensity in X-Ray diffraction studies. Spray-dried micronized Simvastatin USP was found to show enhanced drug hydrophilicity and solubility as confirmed by lowering in contact angle and increase in solubility and ease of dispersibility observations. In vitro dissolution testing and intrinsic dissolution rate testing were found to show an increase in drug release from 11% to 79% and 4 mg min-1 cm-2 to 17 mg min-1 cm-2 for drug and Spray-dried micronized Simvastatin USP respectively.
 Conclusion: Media milling in synergism with spray-drying was found to be a prospective solubility enhancement technique for poorly-soluble Simvastatin USP.

Solid State Characterization and Dissolution Enhancement of Nevirapine Cocrystals.

Purpose: Novel cocrystals of nevirapine (NP) were designed and prepared with salicylamide and 3-hydroxy benzoic acid (3-HBA). Methods: The cocrystals were prepared by solvent drop grinding method by adding few drops of acetone to enhance the solubility and dissolution. The drug and cocrystals were characterized by differential scanning calorimetry (DSC) and powder x-ray diffraction (PXRD). The solubility of NP, its wet ground form, and cocrystals were investigated at different pH. Moreover, the effect of surfactant on solubility of cocrystals was also studied. Finally, intrinsic dissolution rate (IDR) and stability of cocrystals was examined. Results: The characterization of cocrystals by DSC and PXRD revealed formation of new solid forms due to changes in thermogram and PXRD pattern. The cocrystal of NP with 3-HBA showed 4.5 folds greater solubility in pH 1.2 buffer and 5.5 folds in 1% Tween 80 as compared to original drug. IDR of cocrystals was higher than the pure drug in 0.1 N hydrochloric acid (HCl). Moreover, cocrystals were found physically stable after 3 months as evident from unchanged IDR. Conclusion: Hence, the present research indicates the new stable solid forms of NP with improved dissolution rate than pure drug.

Comparison of media milling and microfluidization methods for engineering of nanocrystals: a case study

Objective The article focuses on exploring and comparing two top-down methods, i.e. media milling and microfluidization for the fabrication of nanocrystals of rifampicin (RIF), a poorly water-soluble drug in terms of their potential for generation of stable and efficacious nanocrystals. Significance Nanocrystals are often the system of choice for the formulation of poorly water-soluble drugs. The characteristic benefit of nanocrystals lies in their ability to boost the bioavailability of such drugs by enhancing their saturation solubility and dissolution velocity. Nanocrystals can be prepared by either bottom-up or top-down approach. The latter is often preferred due to the feasibility of scale-up and economical nature. Hence, the emphasis is on these methods. Methods Stable RIF nanocrystals (RIF NCs) were developed and optimized using media milling and microfluidizer method by incorporating a suitable surfactant/stabilizer. The developed nanocrystals were evaluated for their saturation solubility, in vitro dissolution, solid-state characteristics, morphology, intrinsic dissolution rate, and short-term physical stability. Results Both the methods were found to be equally efficient in terms of development of stable RIF NCs, while in terms of processing time and efficacy, microfluidization was found to be advantageous. Amorphization and polymorphic conversion were evident based on the results of solid-state characterization. Furthermore, both formulations exhibited an enhanced solubility and faster dissolution velocity. Conclusion Based on the characterization outcomes, it can be concluded that both the top-down technologies could be successfully applied to develop nanocrystals of poorly water-soluble drugs. However, microfluidization was found to outplay media milling in terms of processing time and drug loading.

Composing Novel Diclofenac Potassium and l-Proline Salt Cocrystal as a Strategy to Increase Solubility and Dissolution

This research dealt with the multicomponent crystal developed from diclofenac potassium and l-proline to improve the pharmaceutical performance of this anti-inflammatory drug. Slow evaporation of the component mixture at a 1:1 M ratio, supported by ultrasonication, yielded a new salt cocrystal, which was characterized using thermal analysis, Karl Fischer titration, infrared spectrophotometry, powder diffractometry, and single crystal diffractometry. This salt cocrystal was confirmed as a tetrahydrate that comprised diclofenac potassium, l-proline, and water (1:1:4), named DKPH. The new salt cocrystal enhanced the solubility of diclofenac potassium by up to 3.56 folds and accelerated the intrinsic dissolution rate of 3.36 folds. It was supported by the solid and solution phase intermolecular interaction study. A different phase, which indicated a monohydrate form of the salt cocrystal, was found from the low humidity chamber during the isotherm sorption study. However, the tetrahydrate, DKPH, was proven as a stable form under ambient conditions.

Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal.

The crystallization of poorly soluble drug molecules with an excipient into new solid phases called cocrystals has gained a considerable popularity in the pharmaceutical field. In this work, the cocrystal approach was explored for a very poorly water soluble antifungal active, itraconazole (ITR), which was, for the first time, successfully converted into this multicomponent solid using an aromatic coformer, terephthalic acid (TER). The new cocrystal was characterized in terms of its solid-state and structural properties, and a panel of pharmaceutical tests including wettability and dissolution were performed. Evidence of the cocrystal formation was obtained from liquid-assisted grinding, but not neat grinding. An efficient method of the ITR–TER cocrystal formation was ball milling. The stoichiometry of the ITR–TER phase was 2:1 and the structure was stabilized by H-bonds. When comparing ITR–TER with other cocrystals, the intrinsic dissolution rates and powder dissolution profiles correlated with the aqueous solubility of the coformers. The rank order of the dissolution rates of the active pharmaceutical ingredient (API) from the cocrystals was ITR–oxalic acid > ITR–succinic acid > ITR–TER. Additionally, the ITR–TER cocrystal was stable in aqueous conditions and did not transform to the parent drug. In summary, this work presents another cocrystal of ITR that might be of use in pharmaceutical formulations.

Improving solubility and intrinsic dissolution rate of ofloxacin API through salt formation via mechanochemical synthesis with diphenic acid

The study focusses on the effect of solubility and intrinsic dissolution rate on the pharmaceutical salt of ofloxacin, a new generation fluoroquinolone antibacterial marketed drug, with the organic acid coformer, diphenic acid produced via mechanochemical synthesis using liquid assisted grinding method. The synthesized cocrystal salt was characterized by single crystal and powder X-ray diffraction, differential scanning calorimetry, and infrared spectroscopy techniques. The crystal structure reveals that, there is proton migration from the coformer to the drug leading to the formation of salt via charge assisted N–H+···O hydrogen bond interactions. The aqueous solubility of the drug and its corresponding salt were determined in neutral phosphate buffer medium (pH = 7) at 25 °C using UV–Vis absorption spectroscopy, while dissolution experiments were carried out at 37 °C bath temperature and neutral phosphate buffer conditions. Interestingly it has been observed that the aqueous solubility and intrinsic dissolution rate of the salt form of ofloxacin has enhanced significantly compared to the parent drug and this is expected to have implications in the bioavailability of the drug in different formulations related to the utilization of this drug.

The Evaluation of Valsartan Biopharmaceutics Properties.

Solubility, intestinal permeability and dissolution are the main factors that govern the rate and extent of drugs absorption and are directly related to bioavailability. Biopharmaceutics Classification System (BCS) is an important tool which uses in vitro results for comparison with bioavailability in vivo (biowaiver). Valsartan is widely used in the treatment of hypertension and shows different BCS classification in the literature (BCS class II or III). This work proposes the study of valsartan biopharmaceutics properties and its BCS classification. High Performance Liquid Chromatography (HPLC) method was developed and validated to quantify the drug in buffers pH 1.2, 4.5 and 6.8 respectively. Valsartan solubility was determined in these three different media using shake flask method and intrinsic dissolution rate. Evaluation of dissolution profile from coated tablets was conducted. The low solubility (pH 1.2 and 4.5) and high solubility (pH 6.8) were observed for both solubility methods. Permeability data reported from the literature showed that valsartan is a low permeability drug. Valsartan presented the rapid release profile only in pH 6.8. We defined that valsartan is a class IV drug, in disagreement with what has been published so far. It is important to emphasize that the conditions considered here are indicated to define the biopharmaceutics classification by regulatory agencies.

Interaction Map Driven Cocrystallization of Ambrisentan: Structural and Biopharmaceutical Evaluation

The present work deals with the development of cocrystal of ambrisentan (AMT) to improve its biopharmaceutical profile. Full interaction maps (FIM) of AMT were explored to find out the potential sites for hydrogen bonding and prediction of supramolecular synthons. This information was further applied to the screening of amino acids as prospective coformers for cocrystallization of AMT. Mechanochemical reactions have resulted in two cocrystals with l-aspartic acid and glycylglycine (dipeptide). The crystal structural analysis revealed that the hydrogen-bonding pattern in the developed cocrystals corroborated well with the predicted supramolecular synthons. The developed cocrystals showed a remarkable improvement in solubility, intrinsic dissolution rate, and in vivo systemic absorption as compared to the parent drug. Complementarily, Hirshfeld surface maps together with crystal features established a good structural–performance correlation of the developed cocrystals. Thus, the systematic cocrystallization driven by structural informatics tools is valuable in the development of novel solid forms with improved biopharmaceutical attributes.

Intrinsic Dissolution Rate Profiling of Poorly Water-Soluble Compounds in Biorelevant Dissolution Media.

The intrinsic dissolution rate (IDR) of active pharmaceutical ingredients (API) is a key property that aids in early drug development, especially selecting formulation strategies to improve dissolution and thereby drug absorption in the intestine. Here, we developed a robust method for rapid, medium throughput screening of IDR and established the largest IDR dataset in open literature to date that can be used for pharmaceutical computational modeling. Eighteen compounds with diverse physicochemical properties were studied in both fasted and fed state simulated intestinal fluids. Dissolution profiles were measured in small-scale experimental assays using compound suspensions or discs. IDR measurements were not solely linked to API solubility in either dissolution media. Multivariate data analysis revealed that IDR strongly depends on compound partitioning into bile salt and phospholipid micelles in the simulated intestinal fluids, a process that in turn is governed by API lipophilicity, hydrophobicity, and ionization.

Alternate solid form synthesis, characterization and stability of phosphodiesterase 4 inhibitor

Abstract Apremialst is a phosphodiesterase 4 (PDE 4) inhibitor. It is used for the treatment of psoriatic arthritis. It is a low soluble and low permeable BCS class IV drug. In the current study, Apremilast alternate solid form (amorphous) is synthesized to address the low solubility issue. The synthesis consists of antisolvent precipitation technique using n-heptane as an antisolvent and acetone as a solvent. The obtained amorphous form has successfully scaled up to 100 g using same method. The synthesized amorphous form is characterized using PXRD, DSC, TGA, Dynamic Vapour Sorption analyser (DVS) and HPLC technique. X-ray halo pattern along with MDSC glass transition temperature of 77.63 °C (I) are the evidence for the amorphous nature of the Apremilast solid form and stability of the amorphous form. Dynamic water vapour sorption analysis is revealed the ease of handling property of the amorphous solid form with slightly hygroscopic nature. Amorphous form had shown multi fold solubility advantages over the Apremialst counterpart marketed crystalline Form-B in water and biological compartment related USP buffers. Intrinsic dissolution rate of amorphous form also has the same advantage. The prepared amorphous form is robust to pharmaceutical process operations like milling, compaction, drying and high humidity. Appremilast amorphous form is stable for 6 months at 40 °C and 75% RH for 6 months. In the light of current studies, amorphous form of the Apremilast may be taken up for the drug product development.

Design and development of a novel fused filament fabrication (FFF) 3D printed diffusion cell with UV imaging capabilities to characterise permeation in pharmaceutical formulations

The present work aimed at designing and developing a novel 3D printed diffusion cell capable of UV imaging using the fused filament fabrication (FFF) method. UV imaging has proven to be very versatile in the area of pharmaceutics giving insights into various phenomena including the dissolution behaviour of dosage forms, intrinsic dissolution rates and the drug precipitation processes. A 3D printed diffusion cell in the similitude of a Franz cell was successfully printed using polylactic acid (PLA) filaments equipped with quartz for the imaging area. A model ibuprofen (IBU) gel formulation was tested by introducing the dosage form through the 3D printed donor compartment. The drug concentration permeated through the skin mimic (silicone membrane) was determined from the 3D printed receptor compartment using UV imaging in real-time. The results showed successful UV imaging of the permeation of IBU gel in the novel diffusion cell potentially negating further analytical testing such as the HPLC process required for Franz cell tests thereby reducing costs. Potential interactions between the drug and filament used in the 3D printed process suggests although this concept can be moved towards commercialisation, care should be taken with choice of filament used in the 3D printing process.

Discovery of a novel and pharmaceutically viable propylene glycol solvate of Idelalisib

Identification of a right solid form of any active pharmaceutical ingredient (API) has become an integral part of research and development irrespective of innovator or generic companies. This is due to an increased focus on the physicochemical properties of the selected solid forms directly relating to its efficacy, safety and bioavailability. Idelalisib is a BCS class II drug with poor solubility and high permeability. Physicochemical properties of Idelalisib (API) have been modified by synthesing a propylene glycol solvate using antisolvent precipitation crystallization method. PXRD, DSC, TGA, GC and MC. Stress, hygroscopicity, characterize the prepared Propylene Glycol solvate and stability testing of novel propylene glycol solvate has shown physical and chemical stability of Idelalisib propylene glycol solvate. The obtained propylene Glycol solvate is stable for six months at 40 °C and 75% RH. The novel propylene Glycol solvate can endure pharmaceutical process pressure and it has intrinsic dissolution rate advantages over marketed Form.

Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties.

Praziquantel (PZQ) is the first-line drug used against schistosomiasis, one of the most common parasitic diseases in the world. A series of crystalline structures including two new polymorphs of the pure drug and a series of cocrystals of PZQ have been discovered and deposited in the Cambridge Structural Database (CSD). This work adds to the list of multicomponent forms of PZQ a relevant example of a racemic hemihydrate (PZQ-HH), obtainable from commercial PZQ (polymorphic Form A) through mechanochemistry. Noteworthy, the formation of the new hemihydrate strongly depends on the initial polymorphic form of PZQ and on the experimental conditions used. The new PZQ-HH has been fully characterized by means of HPLC, Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Hot-Stage Microscopy (SEM), Powder X-Ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), FT-IR, polarimetry, solid-state NMR (SS-NMR), solubility and intrinsic dissolution rate (IDR), and in vitro tests on Schistosoma mansoni adults. The crystal structure was solved from the powder X-ray diffraction pattern and validated by periodic-DFT calculations. The new bioactive hemihydrate was physically stable for three months and showed peculiar biopharmaceutical features including enhanced solubility and a double intrinsic dissolution rate in water in comparison to the commercially available PZQ Form A.

An interlaboratory investigation of intrinsic dissolution rate determination using surface dissolution

The purpose of this study was to conduct an interlaboratory ring-study, with six partners (academic and industrial), investigating the measurement of intrinsic dissolution rate (IDR) using surface dissolution imaging (SDI) equipment. Measurement of IDR is important in pharmaceutical research as it provides characterising information on drugs and their formulations. This work allowed us to assess the SDI’s interlaboratory performance for measuring IDR using a defined standard operating procedure (see supporting information) and six drugs assigned as low (tadalafil, bromocriptine mesylate), medium (carvedilol, indomethacin) and high (ibuprofen, valsartan) solubility compounds. Fasted State Simulated Intestinal Fluid (FaSSIF) and blank FaSSIF (without sodium taurocholate and lecithin) (pH 6.5) were used as media. Using the standardised protocol an IDR value was obtained for all compounds and the results show that the overall IDR rank order matched the solubility rank order. Interlaboratory variability was also examined and it was observed that the variability for lower solubility compounds was higher, coefficient of variation >50%, than for intermediate and high solubility compounds, with the exception of indomethacin in FaSSIF medium. Inter laboratory variability is a useful descriptor for understanding the robustness of the protocol and the system variability. On comparison to another published small-scale IDR study the rank ordering with respect to dissolution rate is identical except for the high solubility compounds. This results indicates that the SDI robustly measures IDR however, no recommendation on the use of one small scale method over the other is made.

Preparation and characterization of a new solid form of praziquantel, an essential anthelmintic drug. Praziquantel racemic monohydrate

Praziquantel (PZQ) is a highly effective low-cost anthelmintic agent used as the first-choice treatment against schistosomiasis. The low solubility of the active is a major drawback for pharmaceutical formulation. A valid approach of the pharmaceutical industry for the improvement of the pharmacotechnical features of the active principles (such as solubility, processability, stability, among others), is the preparation of new solid forms, such as salts, polymorph, and pseudo-polymorph.Herein we report the preparation and characterization of a new solid form PZQ. The PZQ monohydrate (PZQ-MH) was prepared by a solventless procedure from the commercial racemate and the product was characterized at the solid-state employing optical digital microscopy, thermal methods (melting point, differential scanning calorimetry and thermogravimetric analysis), as well as and mid-infrared and near infrared spectroscopies. The chemical structure and content of water were full assessed by 1H nuclear magnetic resonance (NMR) in solution. The amount of water in PZQ-was also determined by different approaches, including thermogravimetric analysis and the loss on drying test. Solid-state 13C NMR (ssNMR) and X-ray powder diffraction (XRPD) completed the structural characterization of the new monohydrate.PZQ-MH showed a crystalline behavior during XRPD experiments and showed relevant differences in spectroscopic, calorimetric, ssNMR and XRPD signals when it was compared with the known crystal (Form A) and amorphous forms of PZQ. The determination of the intrinsic dissolution rate (IDR) of PZQ-MH was carried out as a functional characterization, observing that the new form had slightly higher IDR than Form A.

Crystal Structural Analysis of DL-Mandelate Salt of Carvedilol and Its Correlation with Physicochemical Properties

A 1:1 salt of carvedilol (CVD), an anti-hypertensive drug, with DL-mandelic acid (DL-MA) was crystallized from ethanol and the structure was characterized by X-ray single-crystal diffraction, revealing salt formation by transfer of an acidic proton from the COOH group of MA to the aliphatic (acyclic) secondary amino NH group of CVD. The crystal structure is triclinic, with a P-1 space group and unit cell parameters a = 9.8416(5) Å, b = 11.4689(5) Å, c = 14.0746(7) Å, α = 108.595(8), β = 95.182(7), γ = 107.323(8), V = 1406.95(15) Å3, and Z = 2. The asymmetric unit contained one protonated CVD and one MA anion, linked via an N+–H∙∙∙O¯ strong hydrogen bond and a ratio of 1:1. As previously reported, the thermal, spectroscopic, and powder X-ray diffraction properties of the salt of CVD with DL-MA (CVD_DL-MA) differed from CVD alone. The intrinsic dissolution rate of CVD_DL-MA was about 10.7 times faster than CVD alone in a pH 6.8 buffer.

Enhanced Physical Stability and Synchronized Release of Febuxostat and Indomethacin in Coamorphous Solids.

Coamorphous formulation, a homogeneous monophasic amorphous system composed of multiple components, has been demonstrated as an effective approach for delivering drugs with poor aqueous solubility. In this study, we prepared the coamorphous system composed of two poorly soluble drugs febuxostat (FEB) and indomethacin (IMC) by using cryogenic milling. The combination of these two drugs in the coamorphous form can attain a synergistic effect, especially on gout therapy. Coamorphous solid of FEB and IMC in 1:1molarratio exhibited superior physical stability compared with the individual amorphous components, as evidenced by X-ray powder diffractions after 30days of storage at ambient and elevated temperature. In addition, the FEB-IMC coamorphous system has been demonstrated to show enhanced dissolution performance. The intrinsic dissolution rates of two components in the coamorphous system exhibited the synchronized drug release. Based on the FT-IR spectroscopy, the excellent physical stability and synchronized release of FEB-IMC coamorphous system could be attributed to the heterodimer structure formed by strong hydrogen bonding interactions between these drugs. Furthermore, the supersaturation potential of FEB-IMC coamorphous solids was also investigated through the cosolvent quenching method. The FEB-IMC coamorphous system can effectively inhibit the fast crystallization of FEB in the supersaturated solution. However, the maximum achievable supersaturation of IMC in the coamorphous system decreases to only one fifth of that achieved for the pure amorphous IMC. These results are relevant for understanding the physical stability and complex solution behaviors of the coamorphous formulation.

Crystal structures, dissolution and pharmacokinetic study on a novel phosphodiesterase-4 inhibitor chlorbipram cocrystals.

Cocrystallization of chlorbipram (ChBP), a novel phosphodiesterase-4 (PDE) inhibitor with water insoluble property developed in our lab, was performed to improve the physicochemical properties and bioavailability in the present study. Three new cocrystals with fumaric aicd (FA), gentisic acid (GA) and salicylic acid (SA) as coformers were synthesized and fully characterized by using the combination of multi-techniques. The cocrystals are phase stable even under high humidity conditions. In vitro study indicates that the solubility of ChBP-GA and ChBP-SA cocrystals increase to 3724.4 ± 58.7, 2897.4 ± 81.9 μg/mL in comparison with ChBP (2561.3 ± 150.4 μg/mL), the intrinsic dissolution rates (IDRs) of ChBP-GA and ChBP-SA cocrystals (721.3 ± 8.0, 614.4 ± 13.2 μg/min/cm2) are both higher than ChBP (537.9 ± 12.0 μg/min/cm2). The blood concentration peak values of ChBP-GA and ChBP-SA cocrystals (165.8 ± 50.9, 105.3 ± 35.6 ng/mL) are both higher than ChBP (51.3 ± 15.1 ng/mL) in in vivo evaluation. It presents the same order in in vitro/vivo study: ChBP-GA > ChBP-SA > ChBP > ChBP-FA. ChBP-FA cocrystal presents a longer elimination half life (t1/2 = 10.0 ± 2.6 h), which makes it a potential candidate for prolonged controlled release formulation. ChBP-GA and ChBP-SA cocrystals both present enhanced solubility and bioavailability in comparison with ChBP, making them a better candidate for the solid dosage formulation development.

The role of solid state properties on the dissolution performance of flufenamic acid

Flufenamic acid is a nonsteroidal anti-inflammatory drug characterized by a low solubility and a variable oral bioavailability. Flufenamic acid is present in the commercial products in two polymorphic enantiotropic forms (Form I and III). Bioinequivalence was observed for commercial solid dosage forms due to the different dissolution rate of batches. Aim of this work is the full characterization of the solid state properties of flufenamic acid in order to evidence reasons of its variable dissolution properties. Two different batches of pure drug obtained by different suppliers were fully characterized. In order to evaluate the effect of the technological processes used for tablet production, the powders were submitted to grinding, kneading, and compression. Thermal analysis and X-ray diffraction studies proved that the drug was provided by both suppliers as Form I, Form III is obtained by recrystallization from ethanol or ethanol/water of both batches and no changes were observed after the different mechanical treatments. No difference was observed between the two forms in terms of equilibrium solubility values. Dissolution rate studies evidenced a difference between the two batches due to their different particle size, which disappeared after sieving. Interestingly, a significant difference in terms of intrinsic dissolution rate and surface wettability of the two compacted powders was observed, even after sieving, probably related to a different behavior of the two powder samples under compaction. These results should be taken into account, during a tablet formulation, in order to obtain a reproducible dissolution performance of the drug, regardless of its original supplier.

Effect of Solid Forms on Physicochemical Properties of Valnemulin

To improve the physicochemical properties of valnemulin (VLM), different solid forms formed by VLM and organic acids, including tartaric acid (TAR), fumaric acid (FUM), and oxalic acid (OXA), were successfully prepared and characterized by using differential scanning calorimetry (DSC), scanning electron microscope (SEM), X-ray powder diffraction (XRPD), and Fourier-transform infrared spectroscopy (FT-IR). The excess enthalpy Hex between VLM and other organic acids was calculated by COSMOthermX software and was used to evaluate the probability of forming multi-component solids between VLM and organic acids. By thermal analysis, it was confirmed that multi-component solid forms of VLM were thermodynamically more stable than VLM itself. Through dynamic vapor sorption (DVS) experiments, it was found that three multi-component solid forms of VLM had lower hygroscopicity than VLM itself. Furthermore, the intrinsic dissolution rate of VLM and its multi-component forms was determined in one kind of acidic aqueous medium by using UV-vis spectrometry. It was found that the three multi-component solid forms of VLM dissolved faster than VLM itself.