Solid Dispersions Research Papers - Academia.edu (original) (raw)

The solubility of drugs remains one of the most challenging aspects of formulation development. There are numerous ways to improve the solubility of drugs amongst which the most promising strategy is solid dispersion. Different ratios of sulfathiazole: PVP-K29/32: sodium lauryl sulfate (SLS) were prepared (1:1:0.1, 1:1:0.5, 1:1:1) and various methods were employed to characterize the prepared solid dispersions, namely modulated differential scanning calorimeter, X-ray powder diffraction, Fourier Transformed Infrared Spectroscopy and dissolution studies. Lack of crystallinity was observed in internal and external systems suggesting a loss of crystallinity, whereas the physical mixtures showed a characteristic peak of sulfathiazole. In vitro dissolution results clearly showed that the incorporation of a relatively small amount of surfactants (5, 20 or 33% w/w) into a solid dispersion can improve its dissolution rates compared to binary solid dispersion (SD) alone and pure sulfathiazole. In all ratios solid dispersion internal shows a higher dissolution rate compared to a physical mixture and solid dispersion external which suggests that the way that the surfactant is incorporated into the solid dispersion plays an important role in changing the solubility of a drug. The solubilization mechanism is mainly responsible for this higher dissolution rate when we incorporate the SLS in SD.

- by
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- Dissolution, Solid Dispersions, Drug Solubility
- by Riaz Uddin
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- HPMC, Solid Dispersions, Atorvastatin, Solvent Evaporation Method

Physical instability remains a major concern with amorphous solid dispersions (ASDs). In addition to bulk crystallization inhibition, another potential strategy to improve the physical stability of ASDs is surface engineering. However, coating processes are extremely challenging for ASD microparticles. Herein, we describe for the first time the application of atomic layer coating (ALC), a solvent-free technique, to deposit a pinhole-free, ultra-thin film of aluminum oxide onto the surface of spray-dried ASD particles containing high drug loadings of ezetimibe with hydroxypropyl methylcellulose acetate succinate. ALC affords excellent control over the thickness, uniformity and conformality of the coating at the atomic scale. The freshly prepared coated ASD powders exhibited less agglomeration, a lower hygroscopicity, as well as improved wettability, flowability and compressibility compared to the uncoated samples. Under accelerated storage conditions, crystallization was detected in the uncoated 50% and 70% drug loading ASDs after only a few days, whereas the coated samples showed no evidence of physical instability for two years. Consequently, there was a dramatic decrease in the drug release from the uncoated ASDs during storage, while little change was observed for the coated samples. Using ALC for surface nanocoating of ASD paves the way for the development of higher drug loading ASD without compromising physical stability, thereby reducing the pill burden.

- by Duong Tu
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- Stability, Atomic Layer Deposition, Nanocoating, Solid Dispersions

The current study was aimed to enhance the solubility of poorly soluble drug Candesartan cilexetil using solid dispersion technology and thereby improving its dissolution characteristics. Solid dispersions were formulated by using carriers like polyethylene glycol 6000(hydrophilic polymer), polyvinylpyrrolidone K 30(hygroscopic polymer) and Gelucire 50/13(amphiphilic surfactant) in different drug-to- carrier ratios by solvent evaporation and melting method. The prepared solid dispersions were characterized using differential scanning calorimetry, powder X-ray diffraction and solubility studies. Based on solubility data three drug-to-carrier combinations, polyethylene glycol (1:5), polyvinylpyrrolidone K 30 (1:5) and Gelucire 50/13 (1:1) were selected to formulate into a capsule dosage form equivalent to 8mg of the drug. The capsules were evaluated for its physical parameters like weight variation, disintegration, drug content and in-vitro dissolution studies. Results of dissolution studies showed rapid release of drug from solid dispersions when dispersed in polyvinylpyrrolidone K 30 when compared with pure drug and other formulations. The dissolution profile of chosen capsule was compared with the marketed product and the formulated capsule showed better release profile than the marketed product. Thus solid dispersion technique can be used successfully for enhancement of solubility and dissolution characteristics of Candesartan cilexetil.

- by JPR Solutions
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- Pharmaceutics, Solid Dispersions, Candesartan cilexetil

Ramipril is an ACE inhibitor mainly used for management of mild to severe hypertension and myocardial infarction. The poor solubility and wettability of Ramipril leads to poor dissolution and hence showing variations in bioavailability.The present study is aimed to improve the physicochemical properties of the drug using solid dispersion [SD] techniques. Solid dispersions [SDs] of ramipril were prepared with
different polymers or carriers such as polyvinylpyrrolidone (PVP K25, PVP K30 and PVP K90), polyethylene glycol (PEG 4000 and PEG 6000) at three drug : carrier ratios (1:1), (1:2) and (1:3). Different methods such as melting and kneading methods were used. The formulations were characterized by X-Ray Diffractometry studies, Fourier transform infrared spectroscopy and in vitro dissolution rate studies. In contrast to the slow dissolution rate of pure Ramipril, the dispersion of the drug in the PEG4000 or 6000 considerably enhanced the dissolution rate. Furthermore; Ramipril 10 mg immediate release tablets prepared in a ratio of 1:1 (drug: carrier) by the fusion method has been resulted in an acceptable dissolution results; 91% and 97% for ramipril-
PEG4000 and ramipril-PEG6000 respectively.

- by Ahmed Abd El-Hay
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- Dissolution enhancement, Solid Dispersions

The present research was aimed to develop the meclizine
hydrochloride-polyethylene glycol 20000 solid dispersions to
enhance the solubility and dissolution rate. They were prepared using
solvent evaporation method and evaluated for solubility studies,
drug-carrier compatibility studies and in vitro dissolution studies.
From the solubility studies, formulation F4 was selected to prepare
the fast dissolving tablets and compared with control tablets
(conventional tablets using pure drug). From the results of in vitro
dissolution study, tablets containing polyethylene glycol 20000
showed almost complete drug release within the 15 min. The percent
drug release in 15 min (Q15
) and initial dissolution rate for
formulation F4 was 98.46±1.24%, 6.56%/min. These were very
much higher compared to control tablets (32.49±1.29 %, 2.17%/min).
The relative dissolution rate was found to be 3.03 and dissolution
efficiency was found to be 54.44 and it is increased by 3.4 fold with
F4 formulation compared to control tablets (16.55). Thus the
formulation of polyethylene glycol 20000 solid dispersions is a
suitable method to enhance the solubility and dissolution rate of
meclizine hydrochloride.

Praktikum penentuan Nilai Perbandingan Dispersi (NPD) ini dilaksanakan pada hari Senin tanggal 3 Maret 2014 di Laboratorium Tanah Umum, Jurusan Tanah, Fakultas Pertanian, Universitas Gadjah Mada, Yogyakarta. Metode yang digunakan dalam percobaan ini adalah penentuan debu dan lempung total serta penyebarandebu dan lempung aktual. Nilai Perbandingan Dispersi (NPD) diperoleh dari pembagian berat debu dan lempung actual dengan berat debu dan lempung total. Percobaan ini dilakukan untuk mengetahui ketahanan tanah terhadap erosi. Erosi merupakan kegiatan dispersi dan pengangkutan tanah oleh air tanah yang mengalir di permukaan yang dapat menyebabkan kerusakan lahan. Tingkat ketahanan tanah terhadap erosi berbeda-beda tergantung pada jenis, unsur, dan kemampuan fisik tanah. Dari percobaan menggunakan Nilai Perbandingan Dispersi (NPD) diperoleh NPD Alfisol 15,9%; Entisol 93,87%; Vertisol 12,642%; Ultisol 30,887; Molisol 15,397%.

- by AJ Sidiq
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- Soil Science, Agriculture, Dispersion, NPD

Solid dispersions have engrossed substantial attention as an effectual means of refining the dissolution rate and hence the bioavailability of a variety of hydrophobic drugs. In this review, it is intended to discuss the future prospects related to the area of solid dispersion manufacturing. Improving oral bioavailability of drugs those given as solid dosage forms remains a challenge for the formulation scientists due to solubility problems. The dissolution rate could be the rate-limiting process in the absorption of a drug from a solid dosage form of relatively insoluble drugs. Therefore, increase in dissolution of poorly soluble drugs by solid dispersion technique presents a challenge to the formulation scientists. Solid dispersion techniques have attracted considerable interest of improving the dissolution rate of highly lipophilic drugs thereby improving their bioavailability by reducing drug particle size, improving wettability and forming amorphous particles. This review article discusses the various preparation techniques and characterization for solid dispersion and compiles some of the recent technology transfers in the form of patents.

- by Kanav Midha and +1
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- Pharmacology, Pharmacy, Pharmaceutical Technology, Pharmaceutics

Improvement of bioavailability of hydrophobic drugs is a great challenge. Over the years a variety of solubilization techniques have been studied and widely used, as more than 40% newly drugs are poorly water soluble in pharmaceutical field. To improve such solubility issues, solid dispersion technique is widely used. This article reviews different technologies of solid dispersion, current trends, advantages and criticisms. The remaining portion of this article is focused on various formulations which are marketed by solid dispersion technology.

- by A H M Saifuddin
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- Solid Dispersions

The aim of the present study was to develop a gastro retentive system of telmisartan to prolong its gastric residence time and bioavailability. Non aqueous solvent evaporation method was used to prepare floating microspheres of telmisartan with kollidon SR. Total five formulations were made with varying concentration of kollidon SR. Prepared floating microspheres were subjected to various evaluation parameters, such as particle size determination, SEM, percent yield, entrapment efficiency, bulk and tapped density, compressibility index, angle repose, In vitro floatability, FT-IR study and In vitro drug release. All the formulations displayed good flow properties. In vitro dissolution studies in HCl buffer pH 1.2 were performed to assess the release profile of prepared floating microsphere formulations. All the five formulation displayed sustained release of drug. FT-IR spectra of formulation F3 exhibited all the peaks as similar to the FT-IR spectra of pure drug, rejecting any doubts about the compatibility between drug and the excipients. We can conclude that kollidon SR can be successfully used to prepare floating microspheres of telmisartan to increase its gastric residence time and bioavailability.

- by satish kumar
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- Pharmacology, Chemistry, Pharmacy, Solid Dispersions

Background: The phenomenon which gives rise to a homogenous system, formed by the dissolution of solute in a solvent is known as solubility. Low solubility is the limiting factor in formulation development. Diclofenac being BCS class II drug have low aqueous solubility of 0.00401mg/ml. Amongst various solubility enhancement techniques, solid dispersion is the easiest one. Objective: Present work is primarily focused on the development of solid dispersions of diclofenac through solvent evaporation technique utilizing Eudragit E100 as a carrier. Methods: Solid dispersion consists of at least one active pharmaceutical ingredient as a carrier in solid state. Various methods for preparing solid dispersions includes melt extrusion, fusion lyophilization, spray drying, solvent evaporation, and super critical fluid (SCF) technology. Solvent evaporation technique is used among various solid dispersion methods. Conclusion: The enhanced solubility found to be 0.485mg/ml. The dissolution was performed using USP Type II apparatus was %CDR of pure drug and its solid dispersion in 8 hr were found out to be 45.14926% and 98.04758% respectively. Henceforth, solid dispersion technique results marked solubility enhancement of diclofenac sodium.

Development of solid dispersions of poorly water soluble drugs is one of the most widely used approaches to enhance the solubility as well as dissolution rate. In the current investigation, Ezetimibe is selected as model drug to improve the solubility and dissolution rate by solid dispersion method. Solid dispersions were prepared using solvent evaporation method by incorporating sol plus as carriers in different ratios and evaluated for solubility studies, FT-IR, X-Ray, DSC studies and in vitro dissolution studies. Based on the solubility and drug release studies, formulations different disintegrates are used and the best natural disintegrating agent i.e. Guar gum was selected to prepare the tablets and in vitro dissolution study is done, tablets containing Guar gum showed almost complete drug release within the 12 min. The percent drug release in 12 min (Q12) and initial dissolution rate for formulation F3 was 94.22±1.08%, 9.26%/min. These were very much higher compared to conventional tablets containing pure drug (23.87±1.13%, 2.38%/min). The relative dissolution rate was found to be 2.14 and dissolution efficiency was found to be 67.52 and it is increased by 4.0 fold with F3 formulation compared to conventional tablets. Thus, it is concluded that the formulation of guar gum as disintegrating agent is a suitable approach to improve the solubility and dissolution rate of Ezetimibe than pure form of drug.

- by JPR Solutions
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- Pharmaceutics, Quality Assurance, Solid Dispersions, Formulation development

The present study was aimed to improve the water
solubility and bioavailability of telmisartan by solid dispersion technique.
Telmisartan is 4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-1'-
yl)methyl]-[1,1'-biphenyl]-2-carboxylic acid. Telmisartan is practically
insoluble in water. Telmisartan is an angiotensin II receptor antagonist
(ARB), used in the management of hypertension. Solid dispersions of
telmisartan were prepared by using poly ethylene glycol 4000 and
mannitol as hydrophilic carriers in different weight ratios by solvent
evaporation method. The drug and the solid dispersions were
characterized by saturation solubility studies, in-vitro dissolution study,
Fourier-transform infrared spectroscopy, differential scanning
calorimetry, drug content estimation and stability study. Based on
physical characters and drug release pattern, formulation F2 (1 g drug, 4 g
PEG 4000 and 1 g mannitol) exhibited the best results. The carriers, poly
ethylene glycol 4000 and mannitol were found to be effective in
increasing the aqueous solubility and dissolution rate of telmisartan in
solid dispersions when compared to the pure drug.

- by Ashutosh Dubey
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- Ndds, Telmisartan, Solid Dispersions, BCS CLASS 2AND 4 DRUGS
- by Kranthikumar Namila
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- Crystallography, Supramolecular Chemistry, Dissolution, Solid Dispersions

Interest in air pollution investigation of urban environment due to existence of industrial and commercial activities along with vehicular emission and existence of buildings and streets which setup natural barrier for pollutant dispersion in the urban environment has increased. The air pollution modelling is a multidisciplinary subject when the entire cities are taken under consideration where urban planning and geometries are complex which needs a large software packages to be developed like Operational Street Pollution Model (OSPM), California Line Source model (CALINE series) etc. On overviewing various works it can be summarized that the air pollutant dispersion in urban street canyons and all linked phenomenon such as wind flow, pollutant concentrations, temperature distribution etc. generally depend on wind speed and direction, building heights and density, road width, source and intensity of air pollution, meteorological variables like temperature, humidity etc. A unique and surprising case is observed every time on numerous combinations of these factors. The main aim of this study is to simulate the atmospheric pollutant dispersion for given pollutant like carbon monoxide, sulphur dioxide and nitrogen dioxide and given atmospheric conditions like wind speed and direction. Computational Fluid Dynamics (CFD) simulation for analysing the atmospheric pollutant dispersion is done after natural airflow analysis. Volume rendering is done for variables such as phase 2 volume fraction and velocity with resolution as 250 pixels per inch and transparency as 20%. It can be observed that all the three pollutant namely nitrogen dioxide, sulphur dioxide and carbon monoxide the phase 2 volume fraction changes from 0 to 1. The wind velocity changes from 3.395×10-13 m/s to 1.692×102 m/s. The dispersion of pollutants follow the sequence Sulphur dioxide>Carbon monoxide>Nitrogen dioxide

- by IJIRIS Journal Division and +1
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- Air pollution, Sustainable Rural Development, Sustainable Developments, Air Pollution Control
- by Riaz Uddin
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- Dissolution, Ibuprofen, Polyethylene Glycol, Solid Dispersions

With the view to synthesize and characterize the enhanced pharmaceutical properties of the solid-liquid dispersions of binary drug system through green chemical techniques present communication have been undertaken for detailed investigation of thermodynamic and interfacial properties of benzimidazole(BI)and β. naphthol (βN)binary eutectic and non-eutectic drug dispersions. Eutecticsoliddispersion was observed at a 0.657-mole fraction of β. naphthol (βN)and melting temperature 90C.
Thermodynamic quantities; Partial and Integral excess Gibbs energy (gE), excess enthalpy (hE), excess entropy (sE) of eutectic and non-eutectic dispersions were determined with the help of activity coefficient data. The negative deviation from ideal behaviour has been seen in the system which refers stronger association between unlike molecules during the formation of the binary mix. The negative value of Gibbs free energy of mixing (GM) refers to the mixing for all eutectic and non-eutectic dispersions as spontaneous. The solid-liquid interfacial characteristics.e., the entropy of fusion per unit volume (SV), solid-liquid interfacial energy (), roughness parameter (α), grain boundary energy and roughness parameter (α) of eutectic and non-eutectic solid dispersions have been reported. The size of the critical nucleus at different undercooling has been found in nanoscale, which may be a big significance in the pharmaceutical world. The value of the roughness parameter, α > 2was observed which manifests the faceted and irregular growth leads in the system.

- by MGES Journals and +1
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- Thermodynamics, Pharmaceuticals, Gibbs Free Energy, Organic synthesis of bioactive molecules

This paper presents the design of a photonic crystal fiber, which promises to yield very large optical nonlinearity ~151 W^(-1) km^(-1) at 1.55 μm wavelength. The fiber possess two zero dispersion points whose location can be tuned by varying air hole diameter and hole pitch. The fiber dispersion is anomalous between these two zero dispersion points and its value is moderate. The fiber has been used to numerically simulate optical supercontinuum (SC) generation using low power pump pulses of 50 fs duration at 1.55 μm wavelength. At the end of 15 cm fiber SC broadening of about 1200 nm and 1700 nm can be achieved with pulses of 1 kW and 5 kW peak power respectively.

The microstructure of pharmaceutical semi-crystalline solid dispersions has attracted extensive attention due to its complexity that might result in the diversity in physical stability, dissolution behavior, and pharmaceutical performance of the systems. Numerous factors have been reported that dictate the microstructure of semicrystalline dispersions. Nevertheless, the importance of the complicated conformation of the polymer has never been elucidated. In this study, we investigate the microstructure of dispersions of polyethylene glycol and active pharmaceutical ingredients by small-angle X-ray scattering and high performance differential scanning calorimetry. Polyethylene glycol with molecular weight of 2000 g/mol (PEG2000) and 6000 g/mol (PEG6000) exhibited remarkable discrepancy in the lamellar periodicity in dispersions with APIs which was attributed to the differences in their folding behavior. The long period of PEG2000 always decreased upon aging-induced exclusion of APIs from the interlamellar region of extended chain crystals whereas the periodicity of PEG6000 may decrease or increase during storage as a consequence of the competition between the drug segregation and the lamellar thickening from nonintegral-folded into integral-folded chain crystals. These processes were in turn significantly influenced by the crystallization tendency of the pharmaceutical compounds, drug−polymer interactions, as well as the dispersion composition and crystallization temperature. This study highlights the significance of the polymer conformation on the microstructure of semicrystalline systems that is critical for the preparation of solid dispersions with consistent and reproducible quality.

- by Duong Tu
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- Pharmacy, Microstructure, Polymer Chemistry, Pharmaceutical Technology
- by Jackson A.l.c. Resende and +1
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- Mechanical Engineering, Chemical Engineering, Technology, Pharmaceutical Technology

PREPARATION AND CHARECTERIZATION OF ZOTEPINE SOLID DISPERSIONS BY CYCLODEXTRIN COMPLEXATION
Carmen Popescu1, Prashanth Manda2, Abhishek Juluri2, Leon Zhou1, Michael A. Repka2, S.Narasimha Murthy2.
1Roquette America, Inc, 2211Innovation Dr, Geneva IL, 60134.
2The University of Mississippi School of Pharmacy, University, MS, 38677.
Purpose
Zotepine is a potent atypical antipsychotic drug. Following oral administration, the systemic bioavailability is highly limited owing to its poor aqueous solubility. This project was focusing on Zotepine solubilization by cyclodextrin (CD) complexation using different solid dispersion methods and compares their efficiency.
METHODS
Cyclodextrin Complexation
-cyclodextrin (Kleptose®, CD) and three derivatives, two hydroxypropyl--cyclodextrins (Kleptose® HPB, HPBCD, molar degree of substitution 0.62 and Kleptose® HP, HPCD, MS=0.87) and a methylated--cyclodextrin (Crysmeb, MCD, MS=0.57) were used to complex Zotepine. Solid dispersions were obtained by complexation methods like physical blend (PM), spray drying (SD) and lyophilization (LYO). Based on previous phase solubility evaluation, Zotepine displayed an AL solubilization profile and was complexed at a 1:1 molar ratio.
Characterization by DSC and NMR
Solid dispersions were characterized by DSC (Perkin-Elmer Diamond) for Zotepine: CDs complex formation. NMR spectral data of the API, cyclodextrin and the Zotepine: CDs complex were done in order to check the possible chemical shifts between the drug and cyclodextrin during the process of complexation.
Dissolution Studies
The release kinetics of Zotepine from solid dispersion powders was evaluated by dissolution profile evaluation in artificial saliva as a dissolution medium at 370C and 75 rpm using USP type II apparatus.
RESULTS
Zotepine exhibited a melting endothermic peak around 93°C in the DSC thermogram. The solid dispersions prepared using PM and LYO are revealing higher drug peak intensity when compared to that of the solid dispersions prepared by SD indicating the possibility of reduced crystallinity of the drug (which might be due to of the drug internalization in the cyclodextrin cavity during complexation). The NMR spectral data illustrate a shift in the drug peak which infers an interaction between the drug and cyclodextrin due to the drug cyclodextrin complexation. The spray dried inclusion complexes obtained using HPBCD showed a Zotepine release of ~ 96% whereas in case of Crysmeb, complexes obtained by lyophilization showed a better dissolution profile (~93%) compared to that of the others methods.
Conclusion
Zotepine:HPBCD solid dispersion prepared by spray drying can make this API a very good candidate for tablet formulation with improved drug solubility and dissolution profile. The data obtained following DSC and NMR studies clearly demonstrate the amorphous nature and complexation of the drug with cyclodextrin.

- by Carmen Popescu
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- Cyclodextrin, Solid Dispersions, Cyclodextrins, Solubility Enhancement Techniques

The choice of suitable model in fitting count data poses a challenge to users, when
count data exhibit over- or under-dispersion. Bayesian Dirichlet Process Mixture
Prior of’ Generalized Linear Mixed Models (DPMglmin) is proposed in this study with
the aim that the model wouki adequately fit any data that is under—and over—dispersed.
in this paper, DPMglmm was employed using Wishart prior distribution. Metropolis
Hasting Monte cario Markov Chain (MCMC) was used to draw parameters from
target posterior distribution. Iterated Weighted Least Square (1IVLS) proposal was
used to determine Acceptance Probability in the Metropolis Hasting Monte Carlo
Markov Chain (M—H MCMC) phase. Firstly, simulation study was carried out, the
response counts were obtained from Discrete Weibull distribution and three
covariates were obtained from Unij17?l distribution in each case. Comparison was
drawn among DPMglmmn, Monte Cario Markov Chain of Gene ralied Linear Mixed
Models (MC’MC’glmîn) and Bayesian Discrete Weibull (BD W) for both under-and
oi’er—dispersed count data using simulated data. In addition, a real—lift data was fItted
to frequentist and Bayesian models. Results of the simulation study showed that
DPMglmm outpeiformed MC’MCglmm and BDW frr both over- and under-dispersed
count. Also,DPMglinmn outperformed MCMCglmm and BDW for both over- and
under-dispersed count. it was further shown in this study that frequentist Discrete
Weibull mo deis somnewhat outperformed BDWcibull for over-and under-dispersed
count data. Findings in tu is study revealed the superiority of’ DPMglmmn over
MMcglmm and BDW irrespective of frrnn of dispersion. Therefore, DPMglmm is
recommended to fit count data. In the class of frequentist models, discrete Weibull
should be adopted for fitting count data, irrespective of’ dispersion level and law
points.

- by IAEME Publication
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- Solid Dispersions

The objective of the current study was to enhance dissolution and oral bioavailability of the poorly water-soluble drug, sorafenib (SFN), by solid dispersion (SD) technique using a novel amphiphilic copolymer, polyvinyl caprolactam–polyvinyl acetate–polyethyleneglycol graft copolymer (Soluplus®). The SD formulations were prepared by the spray drying method with SFN, Soluplus, and sodium lauryl sulfate (SLS) at various weight ratios in water. The optimized SD formulation, which showed the highest dissolution rate in distilled water, was further characterized for surface morphology, crystallinity, dissolution in pH 1.2, pH 4.0, and pH 6.8, and pharmacokinetics in rats. Powder X-ray diffraction and differential scanning calorimetry revealed the amorphous form of SFN in the formulation. In addition, at the oral dosage of 20 mg/kg SFN, the SD formulation showed increased Cmax and AUC0–48h by 1.5- and 1.8-fold, compared to those of SFN powder, respectively (p < 0.05). These findings suggest that the preparation of SFN-loaded SD using Soluplus could be a promising strategy for improvement of oral bioavailability of SFN.

- by Duy Hieu Truong
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- Bioavailability, Solid Dispersions, Sorafenib

We report a simple way to obtain polymer-coated multiwalled boron nitride nanotubes (BNNTs) conducted under mild conditions compatible with fragile biopolymers. The approach converts aggregated pristine BNNTs into colloidally stable dispersions in water without requiring treatment at high temperature or in strongly oxidative conditions. The method relies on our experimental observation that glycine (NH2–CH2–COOH, Gly) interacts with BNNTs, in accordance with theoretical calculations. The role of glycine in this process is 2-fold: the Gly amine group binds to the B-sites of BNNTs, while the Gly carboxylic acid function provides ionic anchoring sites for interactions with polyelectrolytes. The formation of Gly-BNNTs proved to be essential, since they readily disperse in water as disentangled objects and spontaneously adsorb polycations, such as chitosan (CH), polyanions, such as hyaluronan (HA), and polyzwitterionic polymers, such as chitosan-phosphorylcholine (CH-PC). Treatment of aqueous dispersions of coarsely coated BNNTs with an immiscible solvent (hexane) resulted in the complete coverage of the BNNT surfaces via oil/water interfacial assembly. This work provides a rapid, mild, and scalable route to water-dispersible biofunctional BNNTs that may serve as drug delivery vehicles or scaffolds in tissue engineering.

Lipid nanoparticles are promising carriers to deliver anticancer agents of low aqueous solubility such as Paclitaxel (PTX). The aim of this work is to improve the efficacy of Paclitaxel through formulation of Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) containing two different liquid lipids. Preparation was done using homogenization and ultrasonication technique. Nanoparticles physical characterization was done by determination of the mean particle size, zeta potential and Transmission electron microscopy (TEM). Entrapment efficiency and Differential Scanning Calorimetry (DSC) was determined. In vitro release and cytotoxicity was done and results were compared to the commercially available product Taxol ® .The mean particle diameter was between 276-314 nm, while zeta potential ranged from-20.2 and-24.9 mV. The entrapment efficiencies of prepared formulae were high(up to 87.6%) and thermal analysis revealed that the drug was in amorphous form. In vitro release through dialysis membrane showed prolonged release. In vitro cytotoxicity assay showed that IC50 of PTX-NLCs was significantly lower than that of Taxol ®. NLC containing Capryol 90 had the best results in entrapment efficiency and lowest IC50. Both SLN and NLC can be potential carriers for prolonged release and to enhance activity of PTX.

- by Shady Swidan
- •
- Pharmaceutical Technology, Drug delivery, Drug Delivery System, Pharmaceutics

Poor solubility is a major challenge that can limit the oral bioavailability of many drugs, including delamanid, a weakly basic nitro-dihydro-imidazooxazole derivative used to treat tuberculosis. Amorphous solid dispersion (ASD) can improve the bioavailability of poorly water-soluble compounds, yet drug crystallization is a potential failure mechanism, particularly as the drug loading increases. The goal of the current study was two-fold: to enhance the stability of amorphous delamanid against crystallization and to improve drug release by developing ASDs containing the salt form of the drug. Various sulfonate salts of delamanid were prepared in amorphous form and evaluated for their tendency to crystallize and undergo chemical degradation following storage at 40 °C/75% relative humidity. Drug release was evaluated by a two-stage dissolution test consisting of an initial low pH stage, followed by transfer to a higher pH medium. For ASDs of the free base, small amounts of crystallinity during preparation were found to limit the drug release. Delamanid salts with sulfonic acids showed considerably improved amorphous stability. Tosylate, besylate, edisylate, and mesylate salts had high glass transition temperatures as well as good chemical and physical stability. In addition, a remarkable improvement in the drug release was observed when ASDs were prepared with these salts in comparison to the free base form. Specifically, ASDs with hydroxypropyl methylcellulose phthalate (HPMCP) at 25% drug loading exhibited near-complete drug release for all four sulfonate salts. These findings suggest that the dual strategy combining salt formation with ASD formation is a promising approach to alter the crystallization tendency and to improve drug release of problematic poorly water-soluble compounds.

- by Duong Tu
- •
- Stability, Amorphous, Solid Dispersions, RELEASE

Objective: The aim of this study was to formulate a new developed solid dispersion (SD) containing fixed dose combination of nalidixic acid and cefdinir (500:300 mg) to improve dissolution rate of poorly soluble drugs via a new mechanism as well as the conventional mechanism of SD represented by the presence of hydrophilic carrier. Methods: Through this objective eight newly developed SD formulas of fixed dose combination of nalidixic acid and cefdinir (500:300 mg) and (polyethylene glycol 6000 and poloxamer 188) in different ratio were prepared, in addition to SD of each drug alone and simple mixture of individual SD (SMSD) prepared by means of fusion technique. Moreover, SDs beside pure drugs, simple mixture, and physical mixture (PM) were characterized by dissolution tests, solubility studies, powder X-ray diffractometer (PXRD), differential scanning calorimetry (DSC), Fourier transform-infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). Results: From in vitro dissolution tests, PXRD, DSC, FT-IR, and SEM; it is indicated the presence of a physical complex between cefdinir and nalidixic acid in their SD containing combination of fixed dose of both drugs. This will affect the crystallinity of the second drug and their dissolution behavior in addition to the conventional mechanism owing to the presence of hydrophilic carrier (poloxamer 188). Conclusion: It was concluded that the newly prepared formula of SD containing fixed dose combination of nalidixic acid and cefdinir will be promising for higher dissolution profile than that from SD of each drug alone or SMSD of each drug.

- by anas alhamdany and +1
- •
- Solid Dispersions
- by Riaz Uddin
- •
- Pharmaceutical Technology, Dissolution, Ibuprofen, Polyethylene Glycol

Mo-Si-B alloys are potential creep resistant materials for accessing harsh loading scenarios beyond Ni-based superalloys due to their excellent mechanical performance at ultra-high temperatures (> 1200°C). Here, we report on the fabrication through laser additive manufacturing of a Mo rich Mo-Si-B alloy with and without dispersion of oxide (La2O3) particles. The major phase in the solidified material is dendritic a-Mo. The inter-dendritic regions contain a mixture of the Mo5 Si3 (T1) þ Mo 5 SiB 2 (T2) phases, and not the expected equilibrium Mo 3 Si þ Mo 5 SiB 2 (T2) phases. This combination of phases is shown to yield improved high temperature creep resistance but was only accessible through by addition of Nb, W or Ti that substitute Mo in the intermetallic phases. Whereas here it is attributed to the large under-cooling in the small melt pool produced during laser processing. We show that this phase mixture, upon annealing, is stable at 1200°C for 200 h. We also demonstrate successful dispersion of oxide particles mainly in the inter-dendritic regions leading to a high indentation fracture toughness of ~18 MPa√m at room temperature. Toughening originates from crack trapping in the ductile a-Mo and the formation of micro-cracks and crack deflection in the vicinity of oxide particles.

- by Dierk Raabe
- •
- Transmission Electron Microscopy, Additive Manufacturing, Creep, Molybdenum
- by Ahmed M Agiba
- •
- Dissolution, Albendazole, Solid Dispersions
- by A H M Saifuddin
- •
- Anti Diabetic Drug, Solid Dispersions, Formulation development
- by A H M Saifuddin
- •
- Solid Dispersions, Formulation development

Carbon nanotubes (CNTs) with its exceptional thermal and mechanical properties hold the promise
of delivering high performance nanocomposite materials. To utilize CNTs as effective reinforcement
in metal nanocomposites, appropriate dispersion and robust interfacial adhesion between individual
CNT and metal matrix have to be certain. This work presents a novel combined technique of
nanoscale dispersion (NSD) of functionalized multiwalled carbon nanotubes (MWCNTs) in copper
(Cu) matrix composite followed by powder injection molding (PIM). MWCNTs contents were varied
from 0 to 10 volume fraction. Evidences on the existence of functional groups and microstructural
analysis of the fabricated nanocomposites were determined using TEM, EDX, FESEM and FTIR.
Thermal conductivity and elasticity measurements were also performed. The results showed that
the impurities of the pristine MWCNTs such as Fe, Ni catalyst, and the amorphous carbon have
been significantly removed after sonication process. FESEM and TEM observations showed high
stability of MWCNTs at elevated temperatures and uniform dispersion of MWCNTs in Cu matrix at
different volume fractions and sintering temperatures (950, 1000 and 1050 C). The experimentally
measured thermal conductivities of Cu/MWCNTs nanocomposites showed remarkable increase
(11.25% higher than pure sintered Cu) with addition of 1 vol.% MWCNTs, while the modulus of elasticity
(Young’s modulus) of Cu/MWCNTs nanocomposites sintered at 1050 C for 2 h was increased
proportionally to the increment in MWCNTs contents.

- by Faiz Ahmad and +2
- •
- Thermal Engineering, Heat Transfer, Carbon Nanotubes, Nanocomposites

The present work explores the use of dispersants in lowering the viscosity of asphalt mastics. The study includes the use of three different types of dispersants during the mixing of fine aggregates with one specific type of polymer-modified asphalt, namely, Novophalt that has been selected for a case study. The effect of the dispersants on the selection of the mixing temperature is elucidated. A distinction is made between a lubricant and a dispersant by observing the rheological behavior of the aggregate-asphalt systems under different conditions. It is also shown that stearic acid which acts more like a lubricant has the potential to lower compaction temperatures during the paving of roads.

- by Dr Aroon Shenoy
- •
- Asphalt, Mixing, Asphalt Pavements, Asphalt material

Rigosertib is a novel anticancer drug in clinical development by Onconova therapeutics, Inc. Currently, it is in pivotal phase III clinical trials for myelodysplastic syndrome (MDS) patients. Chemically, it is a sodium salt of weak acid with low solubility in lower pH solutions. In the preliminary studies, it was found that rigosertib is unstable in acidic conditions and forms multiple degradation products. In this research, drug degradation kinetics of rigosertib were studied in acidic conditions. Rigosertib follows pseudo-first-order general acid catalysis reaction. Cholestyramine, which is a strong anion exchange resin, was used to form complex with drug to improve stability and dissolution in acidic conditions. Drug complex with cholestyramine showed better dissolution profile compared to drug alone. Effect of polyethylene glycol was investigated on the release of drug from the drug resin complex. Polyethylene glycol further improved dissolution profile by improving drug solubility in acidic medium.

- by Hardikkumar Patel
- •
- Cancer, Drug delivery, Dissolution, Solid Dispersions

a School of Pharmacy, Lovely Professional University.
GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS X 1
Pharmacy
Caffeine is a diuretic, antihypertensive, analgesic component. Caffeine is widely used as popular
analgesic in gradient. Curcumin is derived from curcuma longa belonging to family Zingiberaceae. It is
one of the popular chemical constituent having antiulcer effect. Here it is an attempt to enhance bioavaibility by formulation as
solid dispersion granulated tablets. The initial stage ulcer patients can relieve pain and with a herbal wound healing effect of
curcumin may result in eradication of peptic wound. Curcumin can be extracted by cold percolation method with acetone. And
caffeine can be extracted from Cofea Arabica plant with boiling with water followed by chloroform swirling in separating funnel.
Organic part can be removed by evaporation and caffeine can be collected out. Solid dispersion can be prepared by different
grades of polymers like HPMC , PVP with urea. The solid dispersion has a capability of high dissolution rate. Rate of release from
formulation can be studied by dissolution. The drug polymer stability can be studied by keeping them at various humidity range
and temperature. FTIR and XRD may conrm the formulation and fusion of drug in polymer.
ABSTRACT
KEYWORDS : curcumin, peptic ulcers, X Ray diffraction , FTIR, percolation

- by Dr. Simanchal Panda
- •
- Solid Dispersions

Aim: The primary objective of the study is to evaluate solid dispersion (SDs) made into tablets containing Etoricoxib (ECB) and Thiocolchicoside (TCS) for different in vivo parameters and in vitro drug release as an extension of the work described by Annepogu et al., in 2018. Methods: The in vitro study was constructed on various evaluation parameters of SDs of ECB and TCS. From earlier study results, we have selected formula-5 SDs of ECB and TCS for in-vivo study and comparison with marketed ones. Results: Plasma drug availability was performed on 6 healthy rabbits of both sexes (weighing 2.0-2.5 kg). They were aimlessly alienated into 2 groups of alike size by parallel design. Later, the study was HPLC analysis of the drug in the plasma, which involved preparation of the spiked plasma sample, and an analytical technique was established (simple and cost-effective method for ECB and TCS simultaneous estimation). The plasma samples were assessed for pharmacokinetic parameters. Finally, the F-5 formulation was assessed for in vitro drug release by comparison with the marketed preparation (Recox tablets-Hochest Biotech India). Conclusion: The study summarizes that TCS and ECB reached systemic circulation better than the pure drugs, and the kinetic values were appreciable. The drug discharge from the SDs was identical to the marketed one.

Gliclazide is an anti-diabetic drug. It is a BCS class-II (poorly water soluble) drug and its bioavailability is dissolution rate limited. The dissolution rate of the drug was enhanced by using the solid dispersion technique. Solid dispersions were prepared using PVP-K30 (polyvinylpyrrolidone) and hydroxypropyl-β-cyclodextrin (HP BCD) as the hydrophilic carriers. The solid dispersions were characterized by using DSC (Differential scanning calorimetry), XRD (X-ray diffractometry) and FTIR (Fourier transform infrared spectroscopy). Solid dispersions were formulated into tablets. The formulated tablets were evaluated for the quality control parameters and dissolution rates. The solid-dispersion tablets enhanced the dissolution rate of the poorly soluble drug. The optimized formulation showed a 3 fold faster drug release compared to the branded tablet. The XRD studies demonstrated the remarkable reduction in the crystallinity of the drug in the solid dispersion. The faster dissolution rate of the drug from the solid dispersion is attributed to the marked reduction in the crystallinity of the drug. The DSC and FTIR studies demonstrated the absence of the drug-polymer interaction.

- by M Mohan Varma
- •
- Pharmacology, Materials Science, Chemistry, Pharmacy

- by ahmed samy
- •
- Pharmaceutical Technology, Drug delivery, Drug Delivery System, Pharmaceutics

The objective of this study was to compare the physicochemical characteristics, solubility, dissolution, and oral bioavailability of an ezetimibe-loaded solid self-nanoemulsifying drug delivery system (SNEDDS), surface modified solid dispersion (SMSD), and solvent evaporated solid dispersion (SESD) to identify the best drug delivery system with the highest oral bioavailability. For the liquid SNEDDS formulation, Capryol 90, Cremophor EL, and Tween 80 were selected as the oil, surfactant, and cosurfactant, respectively. The nanoemulsion-forming region was sketched using a pseudoternary phase diagram on the basis of reduced emulsion size. The optimized liquid SNEDDS was converted to solid SNEDDS by spray drying with silicon dioxide. Furthermore, SMSDs were prepared using the spray drying technique with various amounts of hydroxypropylcellulose and Tween 80, optimized on the basis of their drug solubility. The SESD formulation was prepared with the same composition of optimized SMSD. T...

- by Omer Mustapha
- •
- Nanomedicine, Nanoparticles, Nanotechnology, Pharmaceutical Chemistry