scholarly journals Solid Dispersions of Gefitinib Prepared by Spray Drying with Improved Mucoadhesive and Drug Dissolution Properties

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Wesam W. Mustafa ◽  
John Fletcher ◽  
Mouhamad Khoder ◽  
Raid G. Alany
Keyword(s):  
Spray Drying ◽  
Kinase Inhibitor ◽  
Solid Dispersions ◽  
Methyl Cellulose ◽  
Inhibitory Effect ◽  
Drug Dissolution ◽  
Sem Images ◽  
Colon Targeting ◽  
Cytotoxicity Studies ◽  
Spray Dried

AbstractGefitinib is a tyrosine kinase inhibitor that is intended for oral administration yet suffers poor bioavailability along with undesirable side effects. To enhance its solubility and allow colon targeting, gefitinib (ZD) and blends of different ratios of polymers (ternary dispersion) were prepared in organic solution, and solid dispersions were generated employing the spray drying (SD) technique. The methylmethacrylate polymer Eudragit S 100 was incorporated for colon targeting; polyvinylpyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) were utilised to improve the solubility of ZD. SEM, DSC, XRPD, FT-IR, dissolution and cytotoxicity studies were undertaken to characterise and evaluate the developed formulations. SEM images revealed that the rod-shaped crystals of ZD were transformed into collapsed spheres with smaller particle size in the spray-dried particles. DSC, FTIR and XRPD studies showed that ZD loaded in the spray-dried dispersions was amorphous. ZD dissolution and release studies revealed that while a significant (P < 0.05) increase in the ZD dissolution and release was observed from HPMC-based solid dispersion at pH 7.2 (up to 95% in 15 h), practically no drug was released at pH 1.2 and pH 6.5. Furthermore, the HPMC-based solid dispersions displayed enhanced mucoadhesive properties compared with PVP-based ones. Interestingly, cell viability studies using the neutral red assay showed that PVP and HPMC-based solid dispersions had no additional inhibitory effect on Caco-2 cell line compared to the pure drug.

scholarly journals Effect of Storage Humidity on Physical Stability of Spray-Dried Naproxen Amorphous Solid Dispersions with Polyvinylpyrrolidone: Two Fluid Nozzle vs. Three Fluid Nozzle

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1074
Author(s):  
Sonal V. Bhujbal ◽  
Yongchao Su ◽  
Vaibhav Pathak ◽  
Dmitry Y. Zemlyanov ◽  
Alex-Anthony Cavallaro ◽  
...  
Keyword(s):  
Spray Drying ◽  
Single Channel ◽  
Solid Dispersions ◽  
Physical Stability ◽  
Volume Ratio ◽  
Amorphous Solid ◽  
Drug Dissolution ◽  
Amorphous Solid Dispersions ◽  
Two Fluid ◽  
Spray Dried

In a spray drying operation, a two-fluid nozzle (2FN) with a single channel is commonly used for atomizing the feed solution. However, the less commonly used three-fluid nozzle (3FN) has two separate channels, which allow spray drying of materials in two incompatible solution systems. Although amorphous solid dispersions (ASDs) prepared using a 3FN have been reported to deliver comparable drug dissolution performance relative to those prepared using a 2FN, few studies have systematically examined the effect of 3FN on the physical stability. Therefore, the goal of this work is to systematically study the physical stability of ASDs that are spray-dried using a 3FN compared to those prepared using the traditional 2FN. For the 2FN, a single solution of naproxen and polyvinylpyrrolidone (PVP) was prepared in a mixture of acetone and water at a 1:1 volume ratio because 2FN allows for only one solution inlet. For the 3FN, naproxen and PVP were dissolved individually in acetone and water, respectively, because 3FN allows simultaneous entry of two solutions. Upon storage of the formulated ASDs at different humidity levels (25%, 55% and 75% RH), naproxen crystallized more quickly from the 3FN ASDs as compared with the 2FN ASDs. 3FN ASDs crystallized after 5 days of storage at all conditions, whereas 2FN ASDs did not crystallize even at 55% RH for two months. This relatively higher crystallization tendency of 3FN ASDs was attributed to the inhomogeneity of drug and polymers as identified by the solid-state Nuclear Magnetic Resonance findings, specifically due to poor mixing of water- and acetone-based solutions at the 3FN nozzle. When only acetone was used as a solvent to prepare drug-polymer solutions for 3FN, the formulated ASD was found to be stable for >3 months of storage (at 75% RH), which suggests that instability of the 3FN ASD was due to the insufficient mixing of water and acetone solutions. This study provides insights into the effects of solvent and nozzle choices on the physical stability of spray-dried ASDs.

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

2019 ◽  
pp. 41-48 ◽  
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.

scholarly journals Improvement in Dissolution of Bosentan Monohydrate by Solid Dispersions Using Spray Drying Technique

2017 ◽  
Vol 4 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Pankaj V. Dangre ◽  
Vikesh B. Sormare ◽  
Mangesh D. Godbole
Keyword(s):  
Spray Drying ◽  
Solid Dispersion ◽  
Large Scale ◽  
Solid Dispersions ◽  
Significant Rise ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Absolute Bioavailability ◽  
Water Soluble Drug ◽  
Peg 4000

Background: Bosentan monohydrate (BM), a dual endothelin receptor antagonist, is indicated for the treatment of patients with pulmonary arterial hypertension (PAH). It is poorly soluble in water, and having absolute bioavailability of 50%. Objective: The aim of the present work is to develop and evaluate the solid dispersions (SD) of a poorly water soluble drug bosentan monohydrate (BM). Method: Solid dispersions (SDs) systems of BM were prepared with Hydroxy propyle β-cyclodextrin (HPβ-CD) and Polyethylene glycol (PEG-4000) polymers using a spray drying technique. Result: The significant rise in a saturation solubility 174.23±1.36 mg/mL; and drug dissolution 95.11±1.22%; was observed with optimized formulation (SD 6). The solid state characterization of optimized formulation (SD 6) by SEM, DSC, and XRPD revealed the absence of crystalline nature of BM in solid dispersion. High dissolution rate of solid dispersion (SD 6) compared with pure drug indicated the increase in dissolution characteristics. Conclusion: In conclusion, our studies illustrated that spray drying technique could be useful large scale producing method to prepare the solid dispersion of bosentan with HP β-CD, which can improve the solubility as well as stability of the formulation.

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 Solvent-Assisted Secondary Drying of Spray-Dried Polymers

2020 ◽  
Vol 37 (8) ◽  
Author(s):  
Kimberly B. Shepard ◽  
April M. Dower ◽  
Alyssa M. Ekdahl ◽  
Michael M. Morgen ◽  
John M. Baumann ◽  
...  
Keyword(s):  
Spray Drying ◽  
Solid Dispersions ◽  
Model Systems ◽  
Process Time ◽  
Drying Methods ◽  
Drying Process ◽  
Free Volume Theory ◽  
Residual Solvent ◽  
Secondary Drying ◽  
Spray Dried

Abstract Purpose The purpose of this work is to introduce solvent-assisted secondary drying, a method used to accelerate the residual solvent removal from spray dried materials. Spray-drying is used to manufacture amorphous solid dispersions, which enhance the bioavailability of active pharmaceutical ingredients (APIs) with low aqueous solubility. In the spray-drying process, API and excipients are co-dissolved in a volatile organic solvent, atomized into droplets through a nozzle, and introduced to a drying chamber containing heated nitrogen gas. The product dries rapidly to form a powder, but small amounts of residual solvent (typically, 1 to 10 wt%) remain in the product and must be removed in a secondary-drying process. For some spray-dried materials, secondary drying by traditional techniques can take days and requires balancing stability risks with process time. Methods Spray-dried polymers were secondary dried, comparing the results for three state-of-the-art methods that employed a jacketed, agitated-vessel dryer: (1) vacuum-only drying, (2) water-assisted drying, or (3) methanol-assisted drying. Samples of material were pulled at various time points and analyzed by gas chromatography (GC) and Karl Fischer (KF) titration to track the drying process. Results Model systems were chosen for which secondary drying is slow. For all cases studied, methanol-assisted drying outperformed the vacuum-only and water-assisted drying methods. Conclusions The observation that methanol-assisted drying is more effective than the other drying techniques is consistent with the free-volume theory of solvent diffusion in polymers.

scholarly journals Controlled Release of Curcumin from HPMC (Hydroxypropyl Methyl Cellulose) Co-Spray-Dried Materials

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Jiao Zheng ◽  
Bo Wang ◽  
Jia Xiang ◽  
Zhengyu Yu
Keyword(s):  
Controlled Release ◽  
Methyl Cellulose ◽  
Release Profile ◽  
N2 Adsorption ◽  
Sem Images ◽  
Hydroxypropyl Methyl Cellulose ◽  
Large Molecular Weight ◽  
Release Property ◽  
Spray Dried

In order to achieve the controlled release of curcumin, HPMC (hydroxypropyl methyl cellulose) was spray dried with curcumin and lactose. The spray-dried materials were pressed into tablets with a diameter of 8 mm, and their release characteristics in vitro were measured. In vitro experiments showed that the release of curcumin from the HPMC mixture was significantly slower due to the sustained-release property of HPMC as a typical excipient. The release profile of curcumin from the HPMC mixture was relatively stable for a controlled release. SEM images show that the HPMC co-spray-dried powders have crumpled surfaces due to the large molecular weight of HPMC. DSC, XRD, FTIR, N2 adsorption, and TGA have been measured for the spray-dried curcumin materials. This work indicates that HPMC can be used as a controlled-release excipient for curcumin preparations.

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

2019 ◽  
pp. 64-70
Author(s):  
Mai Khanfar ◽  
Bashar Al Taani ◽  
Eman Mohammad
Keyword(s):  
Spray Drying ◽  
Solid Dispersion ◽  
Candesartan Cilexetil ◽  
Solid Dispersions ◽  
Porous Silica ◽  
Amorphous Solid ◽  
Silica Particles ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Spray Dried

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.

scholarly journals Hierarchical Particle Approach for Co-Precipitated Amorphous Solid Dispersions for Use in Preclinical In Vivo Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1034
Author(s):  
Luke Schenck ◽  
Christopher Boyce ◽  
Derek Frank ◽  
Sampada Koranne ◽  
Heidi Ferguson ◽  
...  
Keyword(s):  
Spray Drying ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Amorphous Solid Dispersions ◽  
Amorphous Dispersions ◽  
Co Precipitation ◽  
Particle Approach ◽  
Spray Dried

Amorphous solid dispersions (ASD) have become a well-established strategy to improve exposure for compounds with insufficient aqueous solubility. Of methods to generate ASDs, spray drying is a leading route due to its relative simplicity, availability of equipment, and commercial scale capacity. However, the broader industry adoption of spray drying has revealed potential limitations, including the inability to process compounds with low solubility in volatile solvents, inconsistent molecular uniformity of spray dried amorphous dispersions, variable physical properties across batches and scales, and challenges containing potent compounds. In contrast, generating ASDs via co-precipitation to yield co-precipitated amorphous dispersions (cPAD) offers solutions to many of those challenges and has been shown to achieve ASDs comparable to those manufactured via spray drying. This manuscript applies co-precipitation for early safety studies, developing a streamlined process to achieve material suitable for dosing as a suspension in conventional toxicity studies. Development targets involved achieving a rapid, safely contained process for generating ASDs with high recovery yields. Furthermore, a hierarchical particle approach was used to generate composite particles where the cPAD material is incorporated in a matrix of water-soluble excipients to allow for rapid re-dispersibility in the safety study vehicle to achieve a uniform suspension for consistent dosing. Adopting such an approach yielded a co-precipitated amorphous dispersion with comparable stability, thermal properties, and in vivo pharmacokinetics to spray dried amorphous materials of the same composition.

Optimization of Microcrystalline Cellulose PH 101, Lactose, and Kollidon® K 30 To Obtain Co-Processed Excipient Through Spray Drying

2017 ◽  
Vol 7 (2) ◽  
Author(s):  
Kusuma P. ◽  
Syukri Y ◽  
Sholehuddin F. ◽  
Fazzri N. ◽  
Romdhonah . ◽  
...  
Keyword(s):  
Spray Drying ◽  
Microcrystalline Cellulose ◽  
Chemical Change ◽  
Direct Compression ◽  
Flow Properties ◽  
Scanning Calorimetry ◽  
Compression Process ◽  
Infrared Spectrophotometer ◽  
Physical Mixtures ◽  
Spray Dried

The most efficient tablet processing method is direct compression. For this method, the filler-binder can be made by coprocessing via spray drying method. The purpose of this study was to investigate the effect of spray dried co-processing on microcrystalline cellulose (MCC) PH 101, lactose and Kollidon® K 30 as well as to define the optimum proportions. Spray dried MCC PH 101, lactose, and Kollidon® K 30 were varied in 13 different mixture design proportions to obtain compact, free-flowing filler-binder co-processed excipients (CPE). Compactibility and flow properties became the key parameters to determine the optimum proportions of CPE that would be compared to their physical mixtures. The result showed that the optimum proportion of CPE had better compactibility and flow properties than the physical mixtures. The optimum CPE, consisting of only MCC PH 101 and Kollidon® K 30 without lactose, that were characterized using infrared spectrophotometer, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscope (SEM) indicated no chemical change therein. Therefore, this study showed that spray dried MCC PH 101, lactose and Kollidon® K 30 could be one of the filler-binder alternatives for direct compression process.

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