scholarly journals Enhanced Water Solubility and Oral Bioavailability of Paclitaxel Crystal Powders through an Innovative Antisolvent Precipitation Process: Antisolvent Crystallization Using Ionic Liquids as Solvent

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1008 ◽  
Author(s):  
Qilei Yang ◽  
Chang Zu ◽  
Wengang Li ◽  
Weiwei Wu ◽  
Yunlong Ge ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
High Performance ◽  
Water Solubility ◽  
Water Soluble ◽  
Precipitation Process ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Antisolvent Precipitation ◽  
Antisolvent Crystallization ◽  
Artificial Gastric Juice

Paclitaxel (PTX) is a poor water-soluble antineoplastic drug with significant antitumor activity. However, its low bioavailability is a major obstacle for its biomedical applications. Thus, this experiment is designed to prepare PTX crystal powders through an antisolvent precipitation process using 1-hexyl-3-methylimidazolium bromide (HMImBr) as solvent and water as an antisolvent. The factors influencing saturation solubility of PTX crystal powders in water in water were optimized using a single-factor design. The optimum conditions for the antisolvent precipitation process were as follows: 50 mg/mL concentration of the PTX solution, 25 °C temperature, and 1:7 solvent-to-antisolvent ratio. The PTX crystal powders were characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, high-performance liquid chromatography–mass spectrometry, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Raman spectroscopy, solid-state nuclear magnetic resonance, and dissolution and oral bioavailability studies. Results showed that the chemical structure of PTX crystal powders were unchanged; however, precipitation of the crystalline structure changed. The dissolution test showed that the dissolution rate and solubility of PTX crystal powders were nearly 3.21-folds higher compared to raw PTX in water, and 1.27 times higher in artificial gastric juice. Meanwhile, the bioavailability of PTX crystal increased 10.88 times than raw PTX. These results suggested that PTX crystal powders might have potential value to become a new oral PTX formulation with high bioavailability.

scholarly journals Pharmaceutical Salts of Enrofloxacin with Organic Acids

Crystals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 646
Author(s):  
Hong Pang ◽  
Yu-Bin Sun ◽  
Jun-Wen Zhou ◽  
Meng-Juan Xie ◽  
Hao Lin ◽  
...  
Keyword(s):  
High Performance ◽  
Water Solubility ◽  
Antibacterial Drug ◽  
Mixed Solution ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Organic Salts ◽  
X Ray ◽  
Poorly Soluble ◽  
Pharmaceutical Properties

Enrofloxacin is a poorly soluble antibacterial drug of the fluoroquinolones class used in veterinary medicine. The main purpose of this work was to investigate the structural and pharmaceutical properties of new enrofloxacin salts. Enrofloxacin anhydrate and its organic salts with tartaric acid, nicotinic acid and suberic acid formed as pure crystalline anhydrous solids. All the crystals were grown from a mixed solution by slow evaporation at room temperature. These products were then characterized by field-emission scanning electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry. Further, X-ray single crystal diffraction analysis was used to study the crystal structure. The intermolecular interactions and packing arrangements in the crystal structures were studied, and the solubility of these salts in water was determined using high-performance liquid chromatography. The results show that the new salts of enrofloxacin developed in this study exhibited excellent water solubility.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

scholarly journals Effect of DMPA and Molecular Weight of Polyethylene Glycol on Water-Soluble Polyurethane

Polymers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1915 ◽  
Author(s):  
Eyob Wondu ◽  
Hyun Woo Oh ◽  
Jooheon Kim
Keyword(s):  
Molecular Weight ◽  
Contact Angle ◽  
Polyethylene Glycol ◽  
Photoelectron Spectroscopy ◽  
Water Solubility ◽  
Soft Segment ◽  
Water Soluble ◽  
Size Exclusion ◽  
Resonance Spectroscopy ◽  
Scanning Calorimetry

In this study water-soluble polyurethane (WSPU) was synthesized from isophorone diisocyanate (IPDI), and polyethylene glycol (PEG), 2-bis(hydroxymethyl) propionic acid or dimethylolpropionic acid (DMPA), butane-1,4-diol (BD), and triethylamine (TEA) using an acetone process. The water solubility was investigated by solubilizing the polymer in water and measuring the contact angle and the results indicated that water solubility and contact angle tendency were increased as the molecular weight of the soft segment decreased, the amount of emulsifier was increased, and soft segment to hard segment ratio was lower. The contact angle of samples without emulsifier was greater than 87°, while that of with emulsifier was less than 67°, indicating a shift from highly hydrophobic to hydrophilic. The WSPU was also analyzed using Fourier transform infrared spectroscopy (FT-IR) to identify the absorption of functional groups and further checked by X-ray photoelectron spectroscopy (XPS). The molecular weight of WSPU was measured using size-exclusion chromatography (SEC). The structure of the WSPU was confirmed by nuclear magnetic resonance spectroscopy (NMR). The thermal properties of WSPU were analyzed using thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC).

Salts of purine alkaloids caffeine and theobromine with 2,6-dihydroxybenzoic acid as coformer: structural, theoretical, thermal and spectroscopic studies

2021 ◽  
Vol 77 (11) ◽  
Author(s):  
Mateusz Gołdyn ◽  
Anna Komasa ◽  
Mateusz Pawlaczyk ◽  
Aneta Lewandowska ◽  
Elżbieta Bartoszak-Adamska
Keyword(s):  
Hydrogen Bonds ◽  
Water Solubility ◽  
Theoretical Calculations ◽  
Spectroscopic Studies ◽  
X Ray Diffraction ◽  
Dihydroxybenzoic Acid ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Purine Alkaloids ◽  
Vis Spectroscopy

The study of various forms of pharmaceutical substances with specific physicochemical properties suitable for putting them on the market is one of the elements of research in the pharmaceutical industry. A large proportion of active pharmaceutical ingredients (APIs) occur in the salt form. The use of an acidic coformer with a given structure and a suitable pK a value towards purine alkaloids containing a basic imidazole N atom can lead to salt formation. In this work, 2,6-dihydroxybenzoic acid (26DHBA) was used for cocrystallization of theobromine (TBR) and caffeine (CAF). Two novel salts, namely, theobrominium 2,6-dihydroxybenzoate, C7H9N4O2 +·C7H5O4 − (I), and caffeinium 2,6-dihydroxybenzoate, C8H11N4O2 +·C7H5O4 − (II), were synthesized. Both salts were obtained independently by slow evaporation from solution, by neat grinding and also by microwave-assisted slurry cocrystallization. Powder X-ray diffraction measurements proved the formation of the new substances. Single-crystal X-ray diffraction studies confirmed proton transfer between the given alkaloid and 26DHBA, and the formation of N—H...O hydrogen bonds in both I and II. Unlike the caffeine cations in II, the theobromine cations in I are paired by noncovalent N—H...O=C interactions and a cyclic array is observed. As expected, the two hydroxy groups in the 26DHBA anion in both salts are involved in two intramolecular O—H...O hydrogen bonds. C—H...O and π–π interactions further stabilize the crystal structures of both compounds. Steady-state UV–Vis spectroscopy showed changes in the water solubility of xanthines after ionizable complex formation. The obtained salts I and II were also characterized by theoretical calculations, Fourier-transform IR spectroscopy (FT–IR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and elemental analysis.

Formulation and Evaluation of Benidipine Nanosuspension

2021 ◽  
pp. 4111-4116
Author(s):  
Sejal Patel ◽  
Anita P. Patel
Keyword(s):  
Particle Size ◽  
Water Solubility ◽  
Polymer Concentration ◽  
Oral Route ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Scanning Calorimetry ◽  
23 Factorial Design ◽  
Selection Of

In the interest of administration of dosage form oral route is most desirable and preferred method. After oral administration to get maximum therapeutic effect, major challenge is their water solubility. Water insoluble drug indicate insufficient bioavailability as well dissolution resulting in fluctuating plasma level. Benidipine (BND) is poorly water soluble antihypertensive drug has lower bioavailability. To improve bioavailability of Benidipine HCL, BND nanosuspension was formulated using media milling technique. HPMC E5 was used to stabilize nanosuspension. The effect of different important process parameters e.g. selection of polymer concentration X1(1.25 mg), stirring time X2 (800 rpm), selection of zirconium beads size X3 (0.4mm) were investigated by 23 factorial design to accomplish desired particle size and saturation solubility. The optimized batch had 408 nm particle size Y1, and showed in-vitro dissolution Y2 95±0.26 % in 30 mins and Zeta potential was -19.6. Differential scanning calorimetry (DSC) and FT-IR analysis was done to confirm there was no interaction between drug and polymer.

scholarly journals Enhancement of solubility and dissolution rate of poorly water soluble raloxifene using microwave induced fusion method

2013 ◽  
Vol 49 (3) ◽  
pp. 571-578 ◽  
Author(s):  
Payal Hasmukhlal Patil ◽  
Veena Sailendra Belgamwar ◽  
Pratibha Ramratan Patil ◽  
Sanjay Javerilal Surana
Keyword(s):  
Dissolution Rate ◽  
Hydroxypropyl Methylcellulose ◽  
Microwave Treatment ◽  
Water Soluble ◽  
Fusion Method ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Wetting Properties ◽  
Poorly Soluble ◽  
Poorly Water Soluble

The objective of the present work was to enhance the solubility and dissolution rate of the drug raloxifene HCl (RLX), which is poorly soluble in water. The solubility of RLX was observed to increase with increasing concentration of hydroxypropyl methylcellulose (HPMC E5 LV). The optimized ratio for preparing a solid dispersion (SD) of RLX with HPMC E5 LV using the microwave-induced fusion method was 1:5 w/w. Microwave energy was used to prepare SDs. HPMC E5 LV was used as a hydrophilic carrier to enhance the solubility and dissolution rate of RLX. After microwave treatment, the drug and hydrophilic polymer are fused together, and the drug is converted from the crystalline form into an amorphous form. This was confirmed through scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies. These results suggested that the microwave method is a simple and efficient method of preparing SDs. The solubility and dissolution rate of the SDs were increased significantly compared with pure RLX due to the surfactant and wetting properties of HPMC E5 LV and the formation of molecular dispersions of the drug in HPMC E5 LV. It was concluded that the solubility and dissolution rate of RLX are increased significantly when an SD of the drug is prepared using the microwave-induced fusion method.

scholarly journals The Evaluation of Meloxicam Nanocrystals by Oral Administration with Different Particle Sizes

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 421
Author(s):  
Yao Yu ◽  
Yang Tian ◽  
Hui Zhang ◽  
Qingxian Jia ◽  
Xuejun Chen ◽  
...  
Keyword(s):  
Particle Size ◽  
Water Solubility ◽  
Cell Model ◽  
Particle Sizes ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Laser Scattering ◽  
Transport Studies ◽  
Transmission Electron ◽  
Transmission And Absorption

Meloxicam (MLX) is a non-steroidal anti-inflammatory drug used to treat rheumatoid arthritis and osteoarthritis. However, its poor water solubility limits the dissolution process and influences absorption. In order to solve this problem and improve its bioavailability, we prepared it in nanocrystals with three different particle sizes to improve solubility and compare the differences between various particle sizes. The nanocrystal particle sizes were studied through dynamic light scattering (DLS) and laser scattering (LS). Transmission electron microscopy (TEM) was used to characterize the morphology of nanocrystals. The sizes of meloxicam-nanocrystals-A (MLX-NCs-A), meloxicam-nanocrystals-B (MLX-NCs-B), and meloxicam-nanocrystals-C (MLX-NCs-C) were 3.262 ± 0.016 μm, 460.2 ± 9.5 nm, and 204.9 ± 2.8 nm, respectively. Molecular simulation was used to explore the distribution and interaction energy of MLX molecules and stabilizer molecules in water. The results of differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) proved that the crystalline state did not change in the preparation process. Transport studies of the Caco-2 cell model indicated that the cumulative degree of transport would increase as the particle size decreased. Additionally, plasma concentration–time curves showed that the AUC0–∞ of MLX-NCs-C were 3.58- and 2.92-fold greater than those of MLX-NCs-A and MLX-NCs-B, respectively. These results indicate that preparing MLX in nanocrystals can effectively improve the bioavailability, and the particle size of nanocrystals is an important factor in transmission and absorption.

scholarly journals Highly Water-Soluble Solid Dispersions of Honokiol: Preparation, Solubility, and Bioavailability Studies and Anti-Tumor Activity Evaluation

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 573 ◽  
Author(s):  
Wang ◽  
Wu ◽  
Wang ◽  
Wang ◽  
Zhao
Keyword(s):  
Water Solubility ◽  
Solid Dispersions ◽  
Drug Formulation ◽  
Water Soluble ◽  
Oral Drug ◽  
Diphenyltetrazolium Bromide ◽  
Soluble Solid ◽  
Artificial Gastric Juice ◽  
The Relationship ◽  
Anti Tumor Activity

Honokiol (HK), a well-tolerated natural product, has many multiple pharmacological activities. However, its poor water solubility and low bioavailability limit its clinical application and development. The aim of this research was to prepare the solid dispersion (SD) formulation of honokiol (HK) with poloxamer-188 (PLX) as the carrier, thereby improving its solubility and oral bioavailability. Firstly, by investigating the relationship between the addition amount of the PLX and the solubility of HK, and the effects of solid dispersions with different ratios of HK–PLX on the solubility of HK, we determined that the optimum ratio of PLX to HK was (1:4). Then, the HK–PLX (1:4) SD of HK was prepared using the solvent evaporation method. The morphology of the obtained HK–PLX (1:4) SD was different from that of free HK. The HK in the HK–PLX (1:4) SD existed in amorphous form and formed intermolecular hydrogen bonds with PLX. Additionally, the solubility values of the HK–PLX (1:4) SD were about 32.43 ± 0.36 mg/mL and 34.41 ± 0.38 mg/mL in artificial gastric juice (AGJ) and in artificial intestinal juice (AIJ), respectively. Compared with free HK, the release rate and the bioavailability was also substantially improved for HK in its SD form. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that the HK–PLX (1:4) SD showed higher inhibition of HepG2 cells than free HK. Taken together, the present study suggests that the HK–PLX (1:4) SD could become a new oral drug formulation with high bioavailability and could produce a better response for clinical applications of HK.

scholarly journals Associated-Extraction Efficiency of Six Cyclodextrins on Various Flavonoids in Puerariae Lobatae Radix

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 93 ◽  
Author(s):  
Tao Feng ◽  
Fan Liu ◽  
Lili Sun ◽  
Hongna Huo ◽  
Xiaoliang Ren ◽  
...  
Keyword(s):  
High Performance ◽  
Water Solubility ◽  
Extraction Efficiency ◽  
Cerebrovascular Diseases ◽  
Water Soluble ◽  
Cyclodextrin Derivatives ◽  
Treatment And Prevention ◽  
Promising Application ◽  
Sulfobutyl Ether ◽  
Processed Products

Puerariae Lobatae Radix (PLR), a well-known herbal medicine, is the root of Pueraria lobata (Willd.) Ohwi and has been employed for the treatment and prevention of cardiovascular and cerebrovascular diseases. The purpose of this study was to compare the associated-extraction efficiency of six cyclodextrins (CDs) on five flavonoids in PLR, namely puerarin, daidzein, daidzin, genistein and genistin, which are the major secondary metabolites, and exhibit low water solubility. The six CDs applied were β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), hydroxypropyl-γ-cyclodextrin (HP-γ-CD), carboxymethyl-β-cyclodextrin (CM-β-CD), and sulfobutyl ether β-cyclodextrin (SBE-β-CD). They can be grouped into one of the following three categories: traditional cyclodextrins (β-CD and γ-CD), water-soluble cyclodextrin derivatives (HP-β-CD and HP-γ-CD) and ionic cyclodextrin derivatives (SBE-β-CD and CM-β-CD). High-performance liquid chromatography (HPLC) was used to analyze the five flavonoids in the original aqueous extracts (OAE) in the presence or absence of various CDs. The associated-extraction efficiency of the various CDs followed the ranking: SBE-β-CD > HP-β-CD > CM-β-CD > HP-γ-CD > γ-CD > β-CD. It was clear that SBE-β-CD presented the highest associated-extraction capability, and it was used to extract the four flavonoids from three PLR products, including raw product, stir- fried product, and product simmered with wheat bran. The results showed that SBE-β-CD could improve the extraction capability of flavonoids, both from the raw product and in processed products of PLR. In conclusion, CDs, especially SBE-β-CD, have a promising application for the associated-extraction of flavonoids from PLR.

Development and Characterization of the Neuroregenerative Xanthohumol C/Hydroxypropyl-β-cyclodextrin Complex Suitable for Parenteral Administration

Planta Medica ◽  
2019 ◽  
Vol 85 (16) ◽  
pp. 1233-1241
Author(s):  
Michael Kirchinger ◽  
Lara Bieler ◽  
Julia Tevini ◽  
Michael Vogl ◽  
Elisabeth Haschke-Becher ◽  
...  
Keyword(s):  
Water Solubility ◽  
Pharmaceutical Research ◽  
Water Soluble ◽  
Complexing Agents ◽  
Cyclodextrin Complex ◽  
Scanning Calorimetry ◽  
In Vivo Experiments ◽  
Strong Candidate

AbstractThe chroman-like chalcone Xanthohumol C, originally found in hops, was demonstrated to be a potent neuroregenerative and neuroprotective natural product and therefore constitutes a strong candidate for further pharmaceutical research. The bottleneck for in vivo experiments is the low water solubility of this chalcone. Consequently, we developed and validated a suitable formulation enabling in vivo administration. Cyclodextrins were used as water-soluble and nontoxic complexing agents, and the complex of Xanthohumol C and 2-hydroxypropyl-β-cyclodextrin was characterized using HPLC, HPLC-MS, NMR, and differential scanning calorimetry. The water solubility of Xanthohumol C increases with increasing concentrations of cyclodextrin. Using 50 mM 2-hydroxypropyl-β-cyclodextrin, solubility was increased 650-fold. Furthermore, in vitro bioactivity of Xanthohumol C in free and complexed form did not significantly differ, suggesting the release of Xanthohumol C from 2-hydroxypropyl-β-cyclodextrin. Finally, a small-scaled in vivo experiment in a rat model showed that after i. p. administration of the complex, Xanthohumol C can be detected in serum, the brain, and the cerebrospinal fluid at 1 and 6 h post-administration. Mean (± SD) Xanthohumol C serum concentrations after 1, 6, and 12 h were determined as 463.5 (± 120.9), 61.9 (± 13.4), and 9.3 (± 0.8) ng/mL upon i. v., and 294.3 (± 22.4), 45.5 (± 0.7), and 13 (± 1.0) ng/mL after i. p. application, respectively. Accordingly, the formulation of Xanthohumol C/2-hydroxypropyl-β-cyclodextrin is suitable for further in vivo experiments and further pharmaceutical research aiming for the determination of its neuroregenerative potential in animal disease models.

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