scholarly journals Two Novel Palbociclib-Resorcinol and Palbociclib-Orcinol Cocrystals with Enhanced Solubility and Dissolution Rate

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 23
Author(s):  
Chenxin Duan ◽  
Wenwen Liu ◽  
Yunwen Tao ◽  
Feifei Liang ◽  
Yanming Chen ◽  
...  
Keyword(s):  
Water Solubility ◽  
Cancer Drug ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Dissolution Rates ◽  
Intrinsic Dissolution ◽  
X Ray ◽  
Enhanced Solubility

Palbociclib (PAL) is an effective anti-breast cancer drug, but its use has been partly restricted due to poor bioavailability (resulting from extremely low water solubility) and serious adverse reactions. In this study, two cocrystals of PAL with resorcinol (RES) or orcinol (ORC) were prepared by evaporation crystallization to enhance their solubility. The cocrystals were characterized by single crystal X-ray diffraction, Hirshfeld surface analysis, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared and scanning electron microscopy. The intrinsic dissolution rates of the PAL cocrystals were determined in three different dissolution media (pH 1.0, pH 4.5 and pH 6.8), and both cocrystals showed improved dissolution rates at pH 1.0 and pH 6.8 in comparison to the parent drug. In addition, the cocrystals increased the solubility of PAL at pH 6.8 by 2–3 times and showed good stabilities in both the accelerated stability testing and stress testing. The PAL-RES cocrystal also exhibited an improved relative bioavailability (1.24 times) than PAL in vivo pharmacokinetics in rats. Moreover, the in vitro cytotoxicity assay of PAL-RES showed an increased IC50 value for normal cells, suggesting a better biosafety profile than PAL. Co-crystallization may represent a promising strategy for improving the physicochemical properties of PAL with better pharmacokinetics.

The preparation, characterization, structure and dissolution analysis of apremilast solvatomorphs

2017 ◽  
Vol 73 (4) ◽  
pp. 305-313 ◽  
Author(s):  
Yun-Deng Wu ◽  
Xiao-Lei Zhang ◽  
Xiao-Hong Liu ◽  
Jian Xu ◽  
Mei Zhang ◽  
...  
Keyword(s):  
Differential Scanning Calorimetry ◽  
Hydrogen Bonding ◽  
Psoriatic Arthritis ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Dissolution Rates ◽  
X Ray ◽  
Similarity Factor ◽  
Hydrogen Bonding Interactions

Apremilast (AP) {systematic name: (S)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-4-acetamidoisoindoline-1,3-dione} is an inhibitor of phosphodieasterase-4 (PDE4) and is indicated for the treatment of adult patients with active psoriatic arthritis. The ability of AP to form solvates has been investigated and three solvatomorphs of AP, namely, the AP ethyl acetate hemisolvate, C22H24N2O7S·0.5C4H8O2, the AP toluene hemisolvate, C22H24N2O7S·0.5C7H8, and the AP dichloromethane monosolvate, C22H24N2O7S·CH2Cl2, were obtained. The three AP solvatomorphs were characterized by X-ray powder diffraction, thermogravimetric analysis and differential scanning calorimetry. Single-crystal X-ray diffraction was used to analyze the structures, crystal symmetry, packing modes, stoichiometry and hydrogen-bonding interactions of the solvatomorphs. In addition, dissolution analyses were performed to study the dissolution rates of different AP solvatomorph tablets in vitro and to make comparisons with commercial apremilast tablets (produced by Celgene); all three solvatomorphs showed similar dissolution rates and similar values of the similarity factor f2 in a comparison of their dissolution profiles.

scholarly journals Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 289
Author(s):  
Debora Zanolla ◽  
Dritan Hasa ◽  
Mihails Arhangelskis ◽  
Gabriela Schneider-Rauber ◽  
Michele R. Chierotti ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Polymorphic Form ◽  
In Vitro Tests ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Experimental Conditions ◽  
Intrinsic Dissolution ◽  
Intrinsic Dissolution Rate ◽  
X Ray ◽  
Enhanced Solubility

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.

scholarly journals Hydrophilic Sugars for Enhancing Dissolution Rate of Cilostazol: Effect of Wet Co-Processing

2020 ◽  
Vol 27 (1) ◽  
pp. 111-120
Author(s):  
Alaa Yosf Bazeed ◽  
Ahmed Nouh ◽  
Ebtessam Ahmed Essa ◽  
Gamal El Maghraby
Keyword(s):  
Aqueous Solubility ◽  
Submicron Particles ◽  
Drug Dissolution ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Swallowing Difficulties ◽  
Fast Disintegrating Tablets

Background: Cilostazol is an anti-platelets drug with considerable antithrombotic effects in vivo. Therefore, it is widely used by elderly patients. However, it suffers from poor bioavailability due to its low aqueous solubility. The objective of this work was to enhance the dissolution of cilostazol with the aim of formulating fast dissolving tablets for geriatrics and those of swallowing difficulties. Methods: Ethanol-assisted co-grinding of cilostazol with sugar-based excipients was adopted. Sucralose and mannitol were used for this purpose as hydrophilic excipient as well as taste improving agents. The obtained products were investigated regarding differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction, scanning electron microscope (SEM) and in vitro drug dissolution. Fast disintegrating tablets were prepared and evaluated. Results: Thermal behavior of the developed products reflected reduced crystallinity, it also suggested possible existence of new crystalline species with sucralose. Eutexia was also suggested for mannitol mixtures, that was supported by X-ray diffraction data. SEM indicated size reduction with the deposition of the drug as submicron particles over the excipient surface. Co-processing markedly improved cilostazol dissolution compared to unprocessed drug. The optimized formulations were successively formulated into fast disintegrating tablets. Conclusion: This investigation introduced the wet grinding strategy with sugar excipients as a platform for the formulation of easy to use tablets with optimum drug release.

scholarly journals PENGEMBANGAN SISTEM PEMBAWA ALBUMIN NANOPARTIKEL UNTUK SILIMARIN DAN KAJIAN SIFAT FISIK SERTA PROFIL PELEPASANNYA SECARA IN VITRO

2017 ◽  
Vol 7 (2) ◽  
pp. 23-29
Author(s):  
Rini Ambarwati ◽  
Heni Rachmawati
Keyword(s):  
Differential Scanning Calorimetry ◽  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Loading Capacity ◽  
X Ray Diffraction ◽  
Silybum Marianum ◽  
Scanning Calorimetry ◽  
X Ray

Silimarin merupakan senyawa flavonolignan yang berasal dari tumbuhan Silybum marianum (Asteraceae). Silimarin memiliki efek farmakologi sebagai antikanker dan hepatoprotektor, tetapi senyawa ini memiliki kelarutan yang rendah dalam air. Tujuan penelitian ini adalah mengembangkan formulasi silimarin dalam sistem pembawa nano dengan teknik desolvasi. Pembawa yang digunakan adalah serum albumin (bovine serum albumin/BSA). Kombinasi silimarin dalam BSA diharapkan dapat meningkatkan efikasi silimarin sebagai anti kanker karena permeabilitas BSA yang lebih baik pada sel kanker. Evaluasi standar terhadap nanopartikel silimarin-BSA meliputi ukuran dan distribusi ukuran partikel, zeta potensial, morfologi nanopartikel, kristalinitas, sifat termal, spektroskopi inframerah, efisiensi penjeratan serta profil pelepasan silimarin dari BSA nanopartikel pada 2 media berbeda (HCl 0,1 N & PBS pH 7,4). Nanopartikel BSA- silimarin memiliki ukuran partikel 174,23 13,94 nm; distribusi ukuran partikel 0,185 0,052; efisiensi penjeratan 90,54 0,098 %; loading capacity 30,18 0,036 % dan zeta potensial -1,62 mV. Hasil analisis menggunakan DSC (differential scanning calorimetry), XRD (X-ray diffraction) dan spektroskopi inframerah menunjukan bahwa nanopartikel silimarin berhasil terenkapsulasi di dalam nanopartikel BSA, dan BSA-silimarin memiliki bentuk amorf. Setelah 1 jam uji pelepasan, terdapat sebanyak 21,89% silimarin terlepas dalam HCl 0,1 N dan 54,84% silimarin terlepas dalam PBS pH 7,4 sehingga dapat disimpulkan bahwa silimarin-BSA memiliki kelarutan yang baik dalam air. Oleh karena itu, perlu dilakukan pengujian lebih lanjut untuk mengkaji akt ivitas serta perilaku silimarin-BSA in vivo untuk mengkonfirmasi data in vitro.

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.

scholarly journals PREPARATION AND CHARACTERIZATION OF NANOCRYSTALS FOR SOLUBILITY AND DISSOLUTION RATE ENHANCEMENT OF PALIPERIDONE USING DIFFERENT HYDROPHILIC CARRIERS: IN VITRO-IN VIVO STUDY

2018 ◽  
Vol 11 (4) ◽  
pp. 393
Author(s):  
Moon Rajkumar ◽  
Gattani Surendra
Keyword(s):  
Dissolution Rate ◽  
Antipsychotic Agent ◽  
Aqueous Solubility ◽  
In Vivo Study ◽  
Scanning Calorimetry ◽  
Antisolvent Precipitation ◽  
Enhanced Solubility ◽  
Pure Drug

 Objective: The objective of this study was to increase the solubility and dissolution rate of paliperidone (PAL) by preparing its nanocrystals using different hydrophilic carriers by antisolvent precipitation technique.Methods: The nanoparticles (NP) were characterized for aqueous solubility, drug content, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, particle size, and in vitro-in vivo analysis.Results: The results showed improved solubility and dissolution rate of NPs when compared to pure drug and physical mixture (PM). Solubility data showed a linear graph giving an indication that there is a gradual increase in the solubility profile of the drug with an increase in concentration of the carriers. At highest concentration, the solubility of NPs with Plasdone S630, Povidone K-25, and PVP K-30 found to be increased by 12 folds, 9 folds and 6 folds, respectively, as compared to pure drug. The release profile of NPs with Plasdone S630 in terms of dissolution efficiency at 60 min (DE60), initial dissolution rate (IDR), amount release in 15 min (Q15 min), and time for 75% release (t75%) shows better results when compared to pure drug, PM, and also NPs with povidone 25 and povidone 30. In vivo study reveals that optimized NPs elicited significant induction of cataleptic behavior which is the indication of antipsychotic agent(s) effect.Conclusion: The process antisolvent precipitation under constant stirring may be a promising method to produce stable PAL NPs with markedly enhanced solubility and dissolution rate due to nanonization with the increased surface area, improved wettability, and reduced diffusion pathway.

Effects of dietary alteration of bicarbonate and magnesium on rat bone

1986 ◽  
Vol 250 (2) ◽  
pp. F302-F307 ◽  
Author(s):  
J. M. Burnell ◽  
C. Liu ◽  
A. G. Miller ◽  
E. Teubner
Keyword(s):  
Crystal Structure ◽  
Bone Formation ◽  
X Ray Diffraction ◽  
X Ray ◽  
Growing Rats ◽  
Final Composition ◽  
Rat Bone

To study the effects of bicarbonate and magnesium on bone, mild acidosis and/or hypermagnesemia were produced in growing rats by feeding ammonium chloride and/or magnesium sulfate. Bone composition, quantitative histomorphometry, and mineral x-ray diffraction (XRD) characteristics were measured after 6 wk of treatment. The results demonstrated that both acidosis (decreased HCO3) and hypermagnesemia inhibited periosteal bone formation, and, when combined, results were summative; and the previously observed in vitro role of HCO3- and Mg2+ as inhibitors of crystal growth were confirmed in vivo. XRD measurements demonstrated that decreased plasma HCO3 resulted in larger crystals and increased Mg resulted in smaller crystals. However, the combined XRD effects of acidosis and hypermagnesemia resembled acidosis alone. It is postulated that the final composition and crystal structure of bone are strongly influenced by HCO3- and Mg2+, and the effects are mediated by the combined influence on both osteoblastic bone formation and the growth of hydroxyapatite.

scholarly journals Development of an Oxcarbazepine Solid Dispersion Using Skimmed Milk to Improve the Solubility and Dissolution Profile

2019 ◽  
Vol 11 (05) ◽  
Author(s):  
M. Shah ◽  
D. Patel
Keyword(s):  
Electron Microscopy ◽  
Solid Dispersion ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Infra Red ◽  
Crystalline Nature ◽  
Skimmed Milk ◽  
Scanning Electron

Oxcarbazepine has low solubility and low oral bioavailability, so it’s a challenge to formulate suitable dosage form. In this present investigation, to improve the dissolution rate and solubility, skimmed milk is used as a carrier. Physical mixers were prepared using various drugs to carrier ratio and spray drying technology was used to develop solid dispersion with the carrier. Various techniques were used to characterize the solid dispersion immediately after they were made which includes differential scanning calorimetry, scanning electron microscopy, fourier transform infra- red spectroscopy, X-ray diffraction and in-vitro dissolution profiles. The differential scanning calorimetry thermograms of raw drug indicated of its anhydrous crystalline nature. In thermograms of solid dispersion, the characteristic peak was absent suggesting the change from crystalline nature to amorphous form. X-ray diffraction confirmed those results. X-ray diffraction results of raw drug showed highly intense peak characteristic of its crystalline nature where solid dispersion showed less intense, more diffused peak indicating the change in crystalline form. Fourier transforms infra-red spectroscopy studies showed there was no interaction between drug and carrier. Scanning electron microscopy support the amorphous nature of mixer. The whole formulation showed distinct enhancement in the drug release behavior and solubility. The optimum oxcarbazepine to skimmed milk ratio 1:3 enhances the in-vitro drug release by 3.5 fold and also show distinct increase in solubility. It was concluded that for improvement of solubility of poorly water soluble oxcarbazepine, skimmed milk powder as a carrier can be utilize very well.

Thermosensitive In Situ Gel Containing Luteolin Micelles is a Promising Efficient Agent for Colorectal Cancer Peritoneal Metastasis Treatment

2020 ◽  
Vol 16 (1) ◽  
pp. 54-64 ◽  
Author(s):  
Yuzhu Hu ◽  
Xiaoye Chen ◽  
Zongyuan Li ◽  
Songping Zheng ◽  
Yongzhong Cheng
Keyword(s):  
Colorectal Cancer ◽  
Drug Release ◽  
Peritoneal Metastasis ◽  
Water Solubility ◽  
Local Therapy ◽  
Cancer Drug ◽  
Poly Ethylene ◽  
Vegetables And Fruits

Luteolin (Lut) is a natural flavonoid mainly extracted from vegetables and fruits. Lut shows great anti-tumor potential in many malignant cancers, which are hindered by poor water solubility and low bioavailability. Peritoneal metastasis is a challenge for colorectal cancer treatment, usually indicating unfavorable prognosis of patients. Methoxy poly(ethylene glycol)-poly(ε-caprolactone) micelles containing Luteolin (Lut-M) and thermosensitive Pluronic®F127 coated Lut-M (Lut-M-F127) were synthesized and applied in the local therapy of colorectal cancer. Drug release study of Lut-M-F127 and Lut-M suggested extended drug release, and the release of Lut from Lut-M-F127 was slower than Lut-M. It was also proved that Lut-M-F127 could transit from solution to gel at body temperature. Moreover, both Lut-Free and Lut-M micelles were capable of inducing tumor cell apoptosis and reducing cell viability in vitro. Our results further demonstrated the therapeutic effect of Lut-M-F127 treatment was much better than that of Lut-M treatment in vivo. Lut-M-F127 has shown strong ability to promote tumor apoptosis, suppress tumor proliferation and block tumor angiogenesis. In summary, Lut-M-F127 formulation may be a very promising treatment option for peritoneal metastasis in colorectal cancer in the future.

scholarly journals Development and In-Vitro Evaluation of pH Responsive Polymeric Nano Hydrogel Carrier System for Gastro-Protective Delivery of Naproxen Sodium

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Rai Muhammad Sarfraz ◽  
Muhammad Rouf Akram ◽  
Muhammad Rizwan Ali ◽  
Asif Mahmood ◽  
Muhammad Usman Khan ◽  
...  
Keyword(s):  
Drug Release ◽  
Naproxen Sodium ◽  
Research Work ◽  
Entrapment Efficiency ◽  
Gravimetric Analysis ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Swelling Behaviour ◽  
X Ray

Current research work was carried out for gastro-protective delivery of naproxen sodium. Polyethylene glycol-g-poly (methacrylic acid) nanogels was developed through free radical polymerization technique. Formulation was characterized for swelling behaviour, entrapment efficiency, Fourier transform infrared (FTIR) spectroscopy, Differential scanning calorimetry (DSC), and Thermal Gravimetric Analysis (TGA), Powder X-ray diffraction (PXRD), Zeta size distribution, and Zeta potential measurements, and in-vitro drug release. pH dependent swelling was observed with maximum drug release at higher pH. PXRD studies confirmed the conversion of loaded drug from crystalline to amorphous form while Zeta size measurement showed size reduction. On the basis of these results it was concluded that prepared nanogels proved an effective tool for gastro-protective delivery of naproxen sodium.

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