ENHANCEMENT OF DISSOLUTION AND STABILITY OF CANDESARTAN CILEXETIL–LOADED SILICA POLYMERS

Objective: To prepare stable amorphous solid dispersions of candesartan cilexetil (CAN) with different types of silica, including non-porous (aerosil 200) and porous silica (sylysia 350) using the spray-drying method. Methods: various ratios of candesartan cilexetil (CAN) were spray dried with aerosil and sylysia. Powder x-ray diffraction (x-ray) differential scanning calorimetry (DSC), SEM were used to characterize the spray dried powders in addition to dissolution and stability studies. Results: X-ray results showed that the spray–dried (CAN) in the prepared solid dispersion were in amorphous form irrespective of the used silica. In (DSC) analysis, the melting peak of spray-dried (CAN-silica) solid dispersion disappeared. Dissolution property of (CAN) was remarkably improved by formulating with silica particles. In comparing the effect of the type of the silica particles, the dissolution rate of (CAN) from the spray-dried (CAN-sylysia) was faster than that (CAN-aerosil 200) irrespective of the drug content. It was also shown that the spray-dried formulation with silica did not recrystallize when storing at severe storage conditions (40 °C, 75% RH) for three months, while spray-dried (CAN) without silica easily re-crystallized under the same conditions. Conclusion: Spray drying of (CAN) with sylysia 350 is an efficient method to enhance the dissolution and stability of the drug.

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Preparation and Characterization of Artemether Solid Dispersion by Spray Drying Technique

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v11i2.4557 ◽

2021 ◽

Vol 11 (2) ◽

pp. 1-5

Author(s):

Dhiraj Dabhade ◽

Kamlesh Wadher ◽

Shrikant Bute ◽

Nikita Naidu ◽

Milind Umekar ◽

...

Keyword(s):

Dissolution Rate ◽

Spray Drying ◽

Solid Dispersion ◽

Solid Dispersions ◽

Amorphous Solid ◽

Study Data ◽

Water Soluble ◽

Amorphous Solid Dispersion ◽

Scanning Calorimetry ◽

Poorly Water Soluble

Introduction: Artemether, a BCS class IV drug (poorly water soluble and poorly permeable, less bioavailability) but is found to be effective against falciparum malaria. Preparation of water soluble formulation could be the technique to improve bioavailability of such drug. The most ideally used technique to enhance the solubility and dissolution of poorly water soluble drugs is Solid dispersion method. Method: The objective of the study was to enhance the solubility and dissolution rate of Artemether by preparing solid dispersions using Soluplus, at different ration of 1:1, 1:2, 1:3 and 1:4 using spray drying technology. Prepared Solid dispersions were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Results: The spray-dried solid dispersions found to be having less crystallinity and showed higher dissolution rates. Solubility study data showed the optimum drug/Soluplus ratio to be 1:3. The dissolution studies of Solid dispersions in 1.2 pH and 6.8 pH buffer showed higher drug release as compared to pure drug. Conclusion: Thus we conclude that an amorphous solid dispersion of Artemether could be a better option for enhancing the dissolution rate of drug Keywords: solid dispersion, artemether, soluplus, solubility enhancement

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Enhanced Oral Bioavailability of Resveratrol by Using Neutralized Eudragit E Solid Dispersion Prepared via Spray Drying

Antioxidants ◽

10.3390/antiox10010090 ◽

2021 ◽

Vol 10 (1) ◽

pp. 90

Author(s):

Eun-Sol Ha ◽

Du Hyung Choi ◽

In-hwan Baek ◽

Heejun Park ◽

Min-Soo Kim

Keyword(s):

Spray Drying ◽

Solid Dispersion ◽

Oral Bioavailability ◽

Solid Dispersions ◽

Amorphous Solid ◽

Pharmaceutical Products ◽

In Vitro Dissolution ◽

Dependent Manner ◽

Amorphous Solid Dispersions ◽

Eudragit E

In this study, we designed amorphous solid dispersions based on Eudragit E/HCl (neutralized Eudragit E using hydrochloric acid) to maximize the dissolution of trans-resveratrol. Solid-state characterization of amorphous solid dispersions of trans-resveratrol was performed using powder X-ray diffraction, scanning electron microscopy, and particle size measurements. In addition, an in vitro dissolution study and an in vivo pharmacokinetic study in rats were carried out. Among the tested polymers, Eudragit E/HCl was the most effective solid dispersion for the solubilization of trans-resveratrol. Eudragit E/HCl significantly inhibited the precipitation of trans-resveratrol in a pH 1.2 dissolution medium in a dose-dependent manner. The amorphous Eudragit E/HCl solid dispersion at a trans-resveratrol/polymer ratio of 10/90 exhibited a high degree of supersaturation without trans-resveratrol precipitation for at least 48 h by the formation of Eudragit E/HCl micelles. In rats, the absolute oral bioavailability (F%) of trans-resveratrol from Eudragit E/HCl solid dispersion (10/90) was estimated to be 40%. Therefore, trans-resveratrol-loaded Eudragit E/HCl solid dispersions prepared by spray drying offer a promising formulation strategy with high oral bioavailability for developing high-quality health supplements, nutraceutical, and pharmaceutical products.

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Compression-Induced Phase Transitions of Bicalutamide

Pharmaceutics ◽

10.3390/pharmaceutics12050438 ◽

2020 ◽

Vol 12 (5) ◽

pp. 438 ◽

Cited By ~ 1

Author(s):

Joanna Szafraniec-Szczęsny ◽

Agata Antosik-Rogóż ◽

Justyna Knapik-Kowalczuk ◽

Mateusz Kurek ◽

Ewa Szefer ◽

...

Keyword(s):

Solid Dispersions ◽

Amorphous Solid ◽

Active Pharmaceutical Ingredient ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Amorphous Solid Dispersions ◽

X Ray ◽

High Propensity ◽

Poorly Soluble ◽

Amorphous Drug

The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively.

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SPRAY DRYING APPROACH IN PREPARATION AND CHARACTERIZATION OF SOLID DISPERSION OF EPROSARTAN MESYLATE

Journal of medical pharmaceutical and allied sciences ◽

10.22270/jmpas.v10i3.1226 ◽

2021 ◽

Vol 10 (3) ◽

pp. 2929-2932

Author(s):

Sachin N Kothawade

Keyword(s):

Spray Drying ◽

Solid Dispersion ◽

Water Solubility ◽

Solid Dispersions ◽

Weight Ratio ◽

Water Soluble ◽

Drying Methods ◽

Scanning Calorimetry ◽

Dispersion Systems ◽

Physicochemical Features

Spray drying methods were used to make solid dispersions of the medication Eprosartan Mesylate, which is poorly water-soluble. X-ray Powder diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry were used to characterize the products' physicochemical features as well as drug-polymer interactions. Eprosartan Mesylate was shown to be dispersed amorphously in both solid dispersion systems, with a drug to polymer weight ratio of 1:4.The drug and polymer created hydrogen bonds, according to the spectrum data. Both techniques utilized in this investigation enhanced Eprosartan Mesylate solubility. Solid dispersions, on the other hand, performed significantly better, dissolving completely in 5 minutes and at a rate that was about 20 times faster than API within the first 15 minutes. Spray drying is a good way to boost the bioavailability of drugs that are poor water solubility.

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FORMULATION AND CHARACTERIZATION OF HPMC AND HPMCAS BASED SOLID DISPERSIONS OF FENOFIBRATE: A COMPARATIVE STUDY

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019v11i4.32592 ◽

2019 ◽

pp. 41-48 ◽

Cited By ~ 1

Author(s):

Ankit Rampal ◽

Manmeet Singh ◽

Shanta Mahajan ◽

Neena Bedi

Keyword(s):

Ir Spectroscopy ◽

Optical Microscopy ◽

Spray Drying ◽

Solid Dispersion ◽

Solid Dispersions ◽

Hydroxypropyl Methylcellulose ◽

Pure Drug ◽

Physical Mixtures ◽

Spray Dried

Objective: The aim of the present study was to investigate the effect of novel polymeric carriers and to develop solid dispersion formulation that could improve in vitro profile of Fenofibrate (FB). Methods: Spray drying technique was used to fabricate solid dispersions with hydrophilic carriers, mainly hydroxypropyl methylcellulose (HPMC) and hydroxypropyl methylcellulose acetate succinate (HPMCAS). Solid dispersions in the form of spray-dried powder were characterized with respect to the pure drug and the corresponding physical mixtures by optical microscopy, x-ray diffraction (XRD), fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC). Size and morphology of optimized solid dispersion were performed by scanning electron microscopy (SEM). Furthermore, in vitro dissolution comparisons were carried out between the optimized solid dispersion against the pure drug and the physical mixtures. Results: Solubility studies demonstrated that the solubility of FB was not affected by pH change. The transformation of crystalline FB into an amorphous solid dispersion powder has been clearly demonstrated by optical microscopy. The molecular dispersion of drug in the dispersion matrix prepared by spray drying was confirmed in XRD and DSC studies. IR spectroscopy was observed with negligible incompatibility of the drug with polymers. Spherical morphology was observed in SEM with no evidence of FB crystals. The prepared solid dispersions exhibited dissolution improvement as compared to the pure drug and spray dried FB in 0.05 M SLS, with HPMCAS as the superior carrier over HPMC. Conclusion: The present study vouches better in vitro profile of FB from spray-dried HPMCAS based solid dispersions.

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

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2020v12i11.39373 ◽

2020 ◽

pp. 114-121

Author(s):

HARITA R. DESAI ◽

ARCHANA B. RAJADHYAX ◽

PURNIMA D. AMIN

Keyword(s):

Differential Scanning Calorimetry ◽

Spray Drying ◽

Scanning Calorimetry ◽

Intrinsic Dissolution ◽

X Ray ◽

Media Milling ◽

Rate Testing ◽

Poorly Soluble ◽

Spray Dried

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.

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Silymarin-solid dispersions: Characterization and influence of preparation methods on dissolution

Acta Pharmaceutica ◽

10.2478/v10007-010-0038-3 ◽

2010 ◽

Vol 60 (4) ◽

pp. 427-443 ◽

Cited By ~ 23

Author(s):

Dalwadi Sonali ◽

Soni Tejal ◽

Thakkar Vaishali ◽

Gandhi Tejal

Keyword(s):

Spray Drying ◽

Solid Dispersion ◽

Solid Dispersions ◽

Amorphous Solid ◽

Precipitation Method ◽

Amorphous Solid Dispersion ◽

Preparation Methods ◽

Hydrogen Bond Formation ◽

Pure Drug ◽

Co Precipitation

Silymarin-solid dispersions: Characterization and influence of preparation methods on dissolution The influence of preparation methodology of silymarin solid dispersions using a hydrophilic polymer on the dissolution performance of silymarin was investigated. Silymarin solid dispersions were prepared using HPMC E 15LV by kneading, spray drying and co-precipitation methods and characterized by FTIR, DSC, XRPD and SEM. Dissolution profiles were compared by statistical and model independent methods. The FTIR and DSC studies revealed weak hydrogen bond formation between the drug and polymer, while XRPD and SEM confirmed the amorphous nature of the drug in co-precipitated solid dispersion. Enhanced dissolution compared to pure drug was found in the following order: co-precipitation > spray drying > kneading methodology (p < 0.05). All preparation methods enhanced silymarin dissolution from solid dispersions of different characteristics. The co-precipitation method proved to be best and provided a stable amorphous solid dispersion with 2.5 improved dissolution compared to the pure drug.

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ENHANCEMENT OF GLIBENCLAMIDE DISSOLUTION RATE BY SOLID DISPERSION METHOD USING HPMC AND PVP

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019v11i5.34137 ◽

2019 ◽

pp. 19-24 ◽

Cited By ~ 1

Author(s):

ARIF BUDIMAN ◽

IYAN SOPYAN ◽

DENIA SEPTY RIYANDI

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Solid Dispersions ◽

Hydroxypropyl Methylcellulose ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

X Ray ◽

Rate Test ◽

Ft Ir

Objective: The aim of this study was to investigate the effects of changing in the proportions of the solid dispersion formula on the dissolution rate of glibenclamide. Methods: Solid dispersions were prepared by solvent evaporation method by using methanol as solvent, hydroxypropyl methylcellulose (HPMC) and polyvinyl pyrrolidone (PVP) as polymers. The prepared product was evaluated by the saturated solubility test and the dissolution rate test. The prepared product was characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) and Scanning Electron Microscopy (SEM). Results: The result showed solid dispersion with a ratio of glibenclamide: PVP: HPMC (1: 3: 6) has the highest increase in solubility (20 fold) compared to pure glibenclamide. This formula also showed an improvement in dissolution rate from 19.9±1.19% (pure glibenclamide) to 99±1.60% in 60 min. Characterization of FT-IR showed that no chemical reaction occurred in solid dispersion of glibenclamide. The results of X-ray diffraction analysis showed an amorphous form in all solid dispersion formulas. The results of DSC analysis showed that endothermic peak melting point of solid dispersion occurred, and the morphology of solid dispersion was more irregular than pure glibenclamide based on SEM characterization Conclusion: The solid dispersion of glibenclamide using PVP: HPMC as carriers can increase the solubility and dissolution rate compared to pure glibenclamide.

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PREPARATION AND CHARACTERIZATION OF SOLID DISPERSION FAMOTIDINE – MANNITOL BY CO-GRINDING METHOD

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i3.16112 ◽

2017 ◽

Vol 10 (3) ◽

pp. 249 ◽

Cited By ~ 1

Author(s):

Lili Fitriani ◽

Sherly Ramadhani ◽

Erizal Zaini

Keyword(s):

Particle Size ◽

Solid Dispersion ◽

Chemical Interaction ◽

Solid Dispersions ◽

Particle Size Analysis ◽

Physical Mixture ◽

Size Analysis ◽

Scanning Calorimetry ◽

X Ray ◽

Grinding Method

ABSTRACTObjective: This study aims to prepare and characterize solid dispersion of famotidine using mannitol to enhance the solubility and dissolution rate.Methods: Solid dispersions were prepared by co-grinding method in 9 formulas. The ratio of famotidine and mannitol was varied (1:1, 1:2, 2:1 w/w),and each ratio was milled at three different times (30, 60, and 90 minutes). The physical mixture was also prepared as comparison at ratio 1:1 w/w.Solid dispersions were characterized by X-ray diffraction analysis, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry(DSC) analysis, scanning electron microscopy (SEM), particle size analysis, solubility, and dissolution rate study. The assay of famotidine was doneusing a UV spectrophotometer.Results: The highest solubility of famotidine in solid dispersion was obtained in F2 (ratio 1:2 and grinding time 30 minutes). The solubility of intactfamotidine, physical mixture, and solid dispersion F2 was 1.630±0.027, 2.757±0.096, and 3.272±0.076 mg/ml, respectively. X-ray diffractogram ofsolid dispersion F2 showed a decrease in the peak intensity of famotidine. Thermogram of DSC showed a decrease of famotidine melting point for bothphysical mixture and solid dispersion. Photomicrograph of SEM indicated the changes in morphology solid dispersion compared to intact substances.FTIR analysis showed no chemical interaction between famotidine and mannitol. The particle size analysis showed a reduction in the particle sizeof the solid dispersion. The dissolution result after 60 minutes was 85.029%, 86.166%, 92.057% for intact famotidine, physical mixture, and soliddispersion F2, respectively.Conclusion: Solid dispersion increased solubility and dissolution rate.Keywords: Solid dispersion, Famotidine, Mannitol, Co-grinding, Solubility.

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