scholarly journals How Does the CO2 in Supercritical State Affect the Properties of Drug-Polymer Systems, Dissolution Performance and Characteristics of Tablets Containing Bicalutamide?

Materials ◽  
2020 ◽  
Vol 13 (12) ◽  
pp. 2848
Author(s):  
Agata Antosik-Rogóż ◽  
Joanna Szafraniec-Szczęsny ◽  
Krzysztof Chmiel ◽  
Justyna Knapik-Kowalczuk ◽  
Mateusz Kurek ◽  
...  
Keyword(s):  
Particle Size ◽  
Binary Systems ◽  
Morphological Changes ◽  
Solid Dispersions ◽  
Drug Dissolution ◽  
Scanning Calorimetry ◽  
State Affect ◽  
Poorly Soluble ◽  
Increasing Demand ◽  
Size And Morphology

The increasing demand for novel drug formulations has caused the introduction of the supercritical fluid technology, CO2 in particular, into pharmaceutical technology as a method enabling the reduction of particle size and the formation of inclusion complexes and solid dispersions. In this paper, we describe the application of scCO2 in the preparation of binary systems containing poorly soluble antiandrogenic drug bicalutamide and polymeric excipients, either Macrogol 6000 or Poloxamer®407. The changes in the particle size and morphology were followed using scanning electron microscopy and laser diffraction measurements. Differential scanning calorimetry was applied to assess thermal properties, while X-ray powder diffractometry was used to determine the changes in the crystal structure of the systems. The dissolution of bicalutamide was also considered. Binary solid dispersions were further compressed, and the attributes of tablets were assessed. Tablets were analyzed directly after manufacturing and storage in climate chambers. The obtained results indicate that the use of supercritical CO2 led to the morphological changes of particles and the improvement of drug dissolution. The flowability of blends containing processed binary systems was poor; however, they were successfully compressed into tablets exhibiting enhanced drug release.

scholarly journals The Self-Assembly Phenomenon of Poloxamers and Its Effect on the Dissolution of a Poorly Soluble Drug from Solid Dispersions Obtained by Solvent Methods

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 130 ◽  
Author(s):  
Joanna Szafraniec ◽  
Agata Antosik ◽  
Justyna Knapik-Kowalczuk ◽  
Krzysztof Chmiel ◽  
Mateusz Kurek ◽  
...  
Keyword(s):  
Spray Drying ◽  
Self Assembly ◽  
Binary Systems ◽  
Solid Dispersions ◽  
Water Soluble ◽  
The Self ◽  
Drug Dissolution ◽  
Reduced Pressure ◽  
Wide Range ◽  
Poorly Soluble

The self-assembly phenomenon of amphiphiles has attracted particular attention in recent years due to its wide range of applications. The formation of nanoassemblies able to solubilize sparingly water-soluble drugs was found to be a strategy to solve the problem of poor solubility of active pharmaceutical ingredients. Binary and ternary solid dispersions containing Biopharmaceutics Classification System (BCS) class II drug bicalutamide and either Poloxamer®188 or Poloxamer®407 as the surface active agents were obtained by either spray drying or solvent evaporation under reduced pressure. Both processes led to morphological changes and a reduction of particle size, as confirmed by scanning electron microscopy and laser diffraction measurements. The increase in powder wettability was confirmed by means of contact angle measurements. The effect of an alteration of the crystal structure was followed by powder X-ray diffractometry while thermal properties were determined using differential scanning calorimetry. Interestingly, bicalutamide exhibited a polymorph transition after spray drying with the poloxamer and polyvinylpyrrolidone (PVP), while the poloxamer underwent partial amorphization. Moreover, due to the surface activity of the carrier, the solid dispersions formed nanoaggregates in water, as confirmed using dynamic light scattering measurements. The aggregates measuring 200–300 nm in diameter were able to solubilize bicalutamide inside the hydrophobic inner parts. The self-assembly of binary systems was found to improve the amount of dissolved bicalutamide by 4- to 8-fold in comparison to untreated drug. The improvement in drug dissolution was correlated with the solubilization of poorly soluble molecules by macromolecules, as assessed using emission spectroscopy.

scholarly journals Solubility and Dissolution Enhancement of Atorvastatin Calcium using Solid Dispersion Adsorbate Technique

2019 ◽  
Vol 28 (2) ◽  
pp. 105-114
Author(s):  
Samer K. Ali ◽  
Eman B. H. Al-Khedairy
Keyword(s):  
Polyethylene Glycol ◽  
Solid Dispersion ◽  
Water Solubility ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Poloxamer 407 ◽  
Dissolution Enhancement ◽  
Drug Solubility ◽  
Scanning Calorimetry ◽  
Poorly Soluble

            Atorvastatin (ATR) is poorly soluble anti-hyperlipidemic drug; it belongs to the class II group according to the biopharmaceutical classification system (BCS) with low bioavailability due to its low solubility. Solid dispersions adsorbate is an effective technique for enhancing the solubility and dissolution of poorly soluble drugs.           The present study aims to enhance the solubility and dissolution rate of ATR using solid dispersion adsorption technique in comparison with ordinary solid dispersion. polyethylene glycol 4000 (PEG 4000), polyethylene glycol 6000 (PEG 6000), Poloxamer188 and Poloxamer 407were used as hydrophilic carriers and Aerosil 200, Aerosil 300 and magnesium aluminium silicate (MAS) as adsorbents.            All solid dispersion adsorbate (SDA) formulas  were prepared in ratios of 1:1:1  (drug: carrier: adsorbent) and evaluated for their water solubility, percentage yield, drug content,  , dissolution, crystal structure using  X-ray powder diffraction (XRD) and Differential Scanning Calorimetry (DSC)  studies and Fourier Transform Infrared Spectroscopy (FTIR) for determination the drug-carrier- adsorbate interaction.                The prepared (SDA) showed significant improvement of drug solubility in all prepared formula. Best result was obtained with formula SDA12(ATR :Poloxamer407 : MAS 1:1:1) that showed 8.07 and 5.38  fold increase in solubility compared to  solubility of pure ATR and  solid dispersion(SD4) (Atorvastatin: Poloxamer 407 1:1) respectively due to increased wettability and reduced crystallinity of the drug which leads to improve drug solubility  and  dissolution .

Fusion as an Approach to Enhance Dissolution Rate of a Poorly Water-Soluble Drug (Curcurmin)

2011 ◽  
Vol 393-395 ◽  
pp. 119-122
Author(s):  
Dong Hua Wan ◽  
Fen Lin ◽  
Qu Xiang Liao
Keyword(s):  
Dissolution Rate ◽  
Drug Loading ◽  
Solid Dispersions ◽  
Gastric Fluid ◽  
Molecular State ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Simulated Gastric Fluid ◽  
Scanning Calorimetry ◽  
Rate Improvement

It’s well known that curcumin is practically insoluble in water. Therefore, to improve the drug dissolution rate, fusion approach was employed to prepare curcumin solid dispersions (SDs) in the carrier Pluronic F68 with three different drug loads. The dissolution rate of curcumin from the SDs was measured at simulated gastric fluid. The concentration of the dissolved drug in the medium was determined by HPLC. The dissolution rates of the formulations were dependent on the drug loading in SDs. 92.2% CUR was dissolved in 10 min from the SDs with 8.97% drug load, whereas the amounts of drug released were 65.8% and 84.2% within 120 min from the SDs with 18.9% and 29.0% drug loads, respectively. The Fourier transform infrared spectra indicated hydrogen bond between the drug and carrier. Furthermore, their physicochemical properties were well investigated using differential scanning calorimetry and X-ray diffraction. In the dispersions containing 8.97% CUR, the drug was in the molecular state. At a composition of approximately 18.9%, CUR was dispersed as micro-fine crystals. These interesting results indicate that the physical states of the drug in the carrier, which are governed by the drug loading, can affect the dissolution rate improvement.

scholarly journals Compression-Induced Phase Transitions of Bicalutamide

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 438 ◽  
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.

scholarly journals Preparation and evaluation of azithromycin binary solid dispersions using various polyethylene glycols for the improvement of the drug solubility and dissolution rate

2016 ◽  
Vol 52 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Ehsan Adeli
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Water Soluble ◽  
Polyethylene Glycols ◽  
X Ray Diffraction ◽  
Drug Release Profile ◽  
Scanning Calorimetry ◽  
Peg 4000 ◽  
Poorly Soluble

ABSTRACT Azithromycin is a water-insoluble drug, with a very low bioavailability. In order to increase the solubility and dissolution rate, and consequently increase the bioavailability of poorly-soluble drugs (such as azithromycin), various techniques can be applied. One of such techniques is "solid dispersion". This technique is frequently used to improve the dissolution rate of poorly water-soluble compounds. Owing to its low solubility and dissolution rate, azithromycin does not have a suitable bioavailability. Therefore, the main purpose of this investigation was to increase the solubility and dissolution rate of azithromycin by preparing its solid dispersion, using different Polyethylene glycols (PEG). Preparations of solid dispersions and physical mixtures of azithromycin were made using PEG 4000, 6000, 8000, 12000 and 20000 in various ratios, based on the solvent evaporation method. From the studied drug release profile, it was discovered that the dissolution rate of the physical mixture, as the well as the solid dispersions, were higher than those of the drug alone. There was no chemical incompatibility between the drug and polymer from the observed Infrared (IR) spectra. Drug-polymer interactions were also investigated using Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Election Microscopy (SEM). In conclusion, the dissolution rate and solubility of azithromycin were found to improve significantly, using hydrophilic carriers, especially PEG 6000.

scholarly journals Impact of HPMCAS on the Dissolution Performance of Polyvinyl Alcohol Celecoxib Amorphous Solid Dispersions

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 541 ◽  
Author(s):  
Marius Monschke ◽  
Karl G. Wagner
Keyword(s):  
Polyvinyl Alcohol ◽  
Dissolution Rate ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
Dissolution Studies ◽  
Rapid Dissolution ◽  
Poorly Soluble ◽  
Inhibitory Potential

Amorphous solid dispersions (ASDs) have been proven to increase the bioavailability of poorly soluble drugs. It is desirable that the ASD provide a rapid dissolution rate and a sufficient stabilization of the generated supersaturation. In many cases, one polymer alone is not able to provide both features, which raises a need for reasonable polymer combinations. In this study we aimed to generate a rapidly dissolving ASD using the hydrophilic polymer polyvinyl alcohol (PVA) combined with a suitable precipitation inhibitor. Initially, PVA and hydroxypropylmethylcellulose acetate succinate (HPMCAS) were screened for their precipitation inhibitory potential for celecoxib in solution. The generated supersaturation in presence of PVA or HPMCAS was further characterized using dynamic light scattering. Binary ASDs of either PVA or HPMCAS (at 10% and 20% drug load) were prepared by hot-melt extrusion and solid-state analytics were conducted using differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and fourier-transformed infrared spectroscopy (FT-IR). The non-sink dissolution studies of the binary ASDs revealed a high dissolution rate for the PVA ASDs with subsequent precipitation and for the HPMCAS ASDs a suppressed dissolution. In order to utilize the unexploited potential of the binary ASDs, the PVA ASDs were combined with HPMCAS either predissolved or added as powder and also formulated as ternary ASD. We successfully generated a solid formulation consisting of the powdered PVA ASD and HPMCAS powder, which was superior in monophasic non-sink dissolution and biorelevant biphasic dissolution studies compared to the binary and ternary ASDs.

Electrosprayed Microparticulate Solid Dispersions Composed of Multiple Components

2014 ◽  
Vol 513-517 ◽  
pp. 259-264
Author(s):  
Wei Qian ◽  
Deng Guang Yu ◽  
Lu Wang ◽  
Shuo Lei Li ◽  
Yi Fan Wang ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Sodium Dodecyl ◽  
Active Pharmaceutical Ingredient ◽  
Scanning Calorimetry ◽  
Electron Microscopic ◽  
Multiple Components ◽  
Rapid Dissolution ◽  
Poorly Soluble ◽  
Average Size

An electrospraying process was developed for fabricating a new type of microparticulate third generation solid dispersions (SDs) composed of multiple components with ferulic acid (FA) as a model active pharmaceutical ingredient. The spraying fluids were the co-dissolving solutions of FA, polyvinylpyrrolidone K25 (PVP K25) and sodium dodecyl sulfate (SDS) in 95% ethanol aqueous solutions. Field emission scanning electron microscopic observations showed that the microparticles had an average size of 1.47 ± 0.75 μm. Results from the differential scanning calorimetry analyses suggested that FA and SDS were distributed in the polymer matrix in an amorphous status owing to the compatibility among components resulted from the second-order interactions, as verified by attenuated total reflectance Fourier transform infrared spectra.In vitrodissolution tests demonstrated that the microparticulate SDs could release all the contained FA within 1 minute, extremely faster than the raw FA particles. It can be concluded that electrospraying is a useful tool for creating new generation SDs composed of multiple components for enhancing the rapid dissolution of poorly soluble drugs.

scholarly journals Enhancement of Aqueous Solubility and Dissolution of Celecoxib through Phosphatidylcholine-Based Dispersion Systems Solidified with Adsorbent Carriers

Pharmaceutics ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 1 ◽  
Author(s):  
Kanghee Jo ◽  
Jae Min Cho ◽  
Hyunjoo Lee ◽  
Eun Kyung Kim ◽  
Hong Chul Kim ◽  
...  
Keyword(s):  
Aqueous Solubility ◽  
Drug Dissolution ◽  
Dissolution Behavior ◽  
X Ray Diffraction ◽  
Hydrophobic Property ◽  
Scanning Calorimetry ◽  
Solid Dosage ◽  
Poorly Soluble ◽  
Highly Hydrophobic ◽  
Hydrophilic Materials

This study aimed to design phosphatidylcholine (PC)-based solid dispersion (SD) systems for enhancing the apparent aqueous solubility and dissolution of celecoxib (CLC), a selective cyclooxygenase-2 inhibitor with a highly hydrophobic property. Although PC-based dispersion formulations considerably increased solubilities of CLC, the lipidic texture of PC was not appropriate as a solid dosage form for oral administration of CLC. To mask the lipidic texture of PC-based matrices, Neusilin® US2, an adsorbent material with a porous structure and large surface area widely used in the pharmaceutical industry, was employed and thereby fully powderized PC-based dispersion formulations could be fabricated. However, PC matrices containing CLC strongly adsorbed to the pores of Neusilin® US2 was not able to be rapidly released. To address this problem, different hydrophilic materials were examined to promote the release of the CLC-dispersed PC matrices from Neusilin® US2. Among tested hydrophilic materials, croscarmellose sodium was the most suitable to facilitate fast drug dissolution from Neusilin® US2 particles, showing significantly enhanced apparent aqueous solubility and dissolution behavior of CLC. Through differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy (FT-IR) analysis, a considerably reduced crystallinity of CLC dispersed in the PC-based dispersion formulations was demonstrated. The PC-based SD formulations developed in this study would be useful for improving the oral bioavailability of poorly soluble drugs such as CLC.

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

2017 ◽  
Vol 10 (3) ◽  
pp. 249 ◽  
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.

scholarly journals Molecular Disorder of Bicalutamide—Amorphous Solid Dispersions Obtained by Solvent Methods

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 194 ◽  
Author(s):  
Joanna Szafraniec ◽  
Agata Antosik ◽  
Justyna Knapik-Kowalczuk ◽  
Karolina Gawlak ◽  
Mateusz Kurek ◽  
...  
Keyword(s):  
Binary Systems ◽  
Solid Dispersions ◽  
Physical Stability ◽  
Amorphous Solid ◽  
Polymorphic Form ◽  
Dissolution Time ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
Intrinsic Dissolution ◽  
Molecular Arrangement

The effect of solvent removal techniques on phase transition, physical stability and dissolution of bicalutamide from solid dispersions containing polyvinylpyrrolidone (PVP) as a carrier was investigated. A spray dryer and a rotavapor were applied to obtain binary systems containing either 50% or 66% of the drug. Applied techniques led to the formation of amorphous solid dispersions as confirmed by X-ray powder diffractometry and differential scanning calorimetry. Moreover, solid–solid transition from polymorphic form I to form II was observed for bicalutamide spray dried without a carrier. The presence of intermolecular interactions between the drug and polymer molecules, which provides the stabilization of molecularly disordered bicalutamide, was analyzed using infrared spectroscopy. Spectral changes within the region characteristic for amide vibrations suggested that the amide form of crystalline bicalutamide was replaced by a less stable imidic one, characteristic of an amorphous drug. Applied processes also resulted in changes of particle geometry and size as confirmed by scanning electron microscopy and laser diffraction measurements, however they did not affect the dissolution significantly as confirmed by intrinsic dissolution study. The enhancement of apparent solubility and dissolution were assigned mostly to the loss of molecular arrangement by drug molecules. Performed statistical analysis indicated that the presence of PVP reduces the mean dissolution time and improve the dissolution efficiency. Although the dissolution was equally affected by both applied methods of solid dispersion manufacturing, spray drying provides better control of particle size and morphology as well as a lower tendency for recrystallization of amorphous solid dispersions.

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