The Correlation between Physical Crosslinking and Water-Soluble Drug Release from Chitosan-Based Microparticles

Microparticles containing water-soluble zidovudine were prepared by spray-drying using chitosan glutamate and beta-glycerophosphate as an ion crosslinker (CF). The Box–Behnken design was applied to optimize the microparticles in terms of their drug loading and release behavior. Physicochemical studies were undertaken to support the results from dissolution tests and to evaluate the impact of the crosslinking ratio on the microparticles’ characteristics. The zidovudine dissolution behavior had a complex nature which comprised two phases: an initial burst effect followed with a prolonged release stage. The initial drug release, which can be modulated by the crosslinking degree, was primarily governed by the dissolution of the drug crystals located on the microparticles’ surfaces. In turn, the further dissolution stage was related to the drug diffusion from the swollen polymer matrix and was found to correlate with the drug loading. Differential Scanning Calorimetry (DSC) studies revealed the partial incorporation of a non-crystallized drug within the polymer matrix, which correlated with the amount of CF. Although CF influenced the swelling capacity of chitosan glutamate microparticles, surprisingly a higher amount of CF did not impact the time required for 80% of the drug to be released markedly. The formulation with the lowest polymer:CF ratio, 3:1, was selected as optimal, providing satisfactory drug loading and displaying a moderate burst effect within the first 30 min of the study, followed with a prolonged drug release of up to 210 min.

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Improved Dissolution of Albendazole from High Drug Loaded Ternary Solid Dispersion: Formulation and Characterization

Dhaka University Journal of Pharmaceutical Sciences ◽

10.3329/dujps.v20i2.57165 ◽

2021 ◽

Vol 20 (2) ◽

pp. 149-158

Author(s):

Shimul Halder ◽

MAK Azad ◽

Hrishik Iqbal ◽

Madhabi Lata Shuma ◽

Eva Rahman Kabir

Keyword(s):

Solid Dispersion ◽

Drug Loading ◽

Aqueous Solubility ◽

Drug Carriers ◽

Physicochemical Characteristics ◽

Water Soluble ◽

Dissolution Behavior ◽

Scanning Calorimetry ◽

High Drug ◽

Enhanced Solubility

Bioavailability of a poorly water-soluble drug, e.g., widely used anthelmintic drug Albendazole (ABZ), is very low and thus, to obtain an optimized therapeutic efficacy, the aqueous solubility of such drugs needs to be enhanced. The objective of this study was to develop an effective high drug-loaded solid dispersion (SD) of ABZ with two biocompatible drug carriers, namely Soluplus® and Ludiflash® to improve its physicochemical characteristics. Equilibrium solubility study was performed to choose the optimum polymer ratio among the formulations and it showed up to 50-fold enhanced solubility compared to crystalline ABZ in water. X-Ray Powder Diffraction (XRPD) and Differential Scanning Calorimetry (DSC) studies of SD-ABZ showed reduced crystallinity of ABZ in the SD. The polymeric carriers, notably Soluplus®, are thought to play a key role in the reduction of crystallinity and molecular polydispersity of ABZ. The dissolution studies in water showed improved dissolution of SD-ABZ compared to crystalline ABZ, with a quick onset of drug release followed by gradual dissolution. However, due to high drug-loading and retention of crystalline ABZ in the sample, the dissolution behavior was not as expected, and may require further studies to optimize the SD-ABZ formulation. Dhaka Univ. J. Pharm. Sci. 20(2): 149-158, 2021 (December)

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Influence on variation in process parameters for the design of xanthan-gum-facilitated ethyl cellulose microparticles for intestinal specific delivery

Science and Engineering of Composite Materials ◽

10.1515/secm-2012-0078 ◽

2013 ◽

Vol 20 (1) ◽

pp. 23-33 ◽

Cited By ~ 3

Author(s):

Subham Banerjee ◽

Aashish Tiwari ◽

Santosh Kumar Yadav ◽

Shiv Sankar Bhattacharya ◽

Aher Vaibhav Dagaji ◽

...

Keyword(s):

Drug Release ◽

Process Parameters ◽

Ethyl Cellulose ◽

Xanthan Gum ◽

Diffusion Mechanism ◽

Fickian Diffusion ◽

Prolonged Release ◽

Scanning Calorimetry ◽

Simulated Intestinal Fluid ◽

The Impact

AbstractXanthan-gum-facilitated aspirin-loaded ethyl cellulose microparticles were prepared by multiple-emulsion solvent evaporation technology and the impact on variation in process parameters was investigated systematically. Scanning electron microscopy was performed to determine the surface morphology of the microparticles before and after dissolution study. X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) analysis were performed, and yield value, swelling study, encapsulation efficiency, flow properties and dissolution profiles of the prepared formulations were evaluated. The size of microparticles varied between 247 and 410 μm, and 58.34% drug entrapment efficiency was achieved depending on the variation in process parameters. The drug release in acid solutions was slower than in alkaline solution. The microparticles provided extended drug release in alkaline dissolution medium, and the drug release was found to be controlled by Fickian diffusion mechanism. XRD and DSC analyses revealed the amorphous nature of drug in the microparticles. FTIR data indicated the stable character of the encapsulated drug in the microparticles. Thus, variation in process parameters showed a slow and prolonged release of aspirin in simulated intestinal fluid.

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Mesoporous Silica Molecular Sieve based Nanocarriers: Transpiring Drug Dissolution Research

Current Pharmaceutical Design ◽

10.2174/1381612822666161026162005 ◽

2017 ◽

Vol 23 (3) ◽

pp. 467-480 ◽

Cited By ~ 8

Author(s):

Satyanarayan Pattnaik ◽

Kamla Pathak

Keyword(s):

Drug Release ◽

Mesoporous Silica ◽

Molecular Sieves ◽

Release Kinetics ◽

Drug Loading ◽

Scale Up ◽

Water Soluble ◽

Drug Dissolution ◽

Water Soluble Drugs ◽

Loading Methods

Background: Improvement of oral bioavailability through enhancement of dissolution for poorly soluble drugs has been a very promising approach. Recently, mesoporous silica based molecular sieves have demonstrated excellent properties to enhance the dissolution velocity of poorly water-soluble drugs. Description: Current research in this area is focused on investigating the factors influencing the drug release from these carriers, the kinetics of drug release and manufacturing approaches to scale-up production for commercial manufacture. Conclusion: This comprehensive review provides an overview of different methods adopted for synthesis of mesoporous materials, influence of processing factors on properties of these materials and drug loading methods. The drug release kinetics from mesoporous silica systems, the manufacturability and stability of these formulations are reviewed. Finally, the safety and biocompatibility issues related to these silica based materials are discussed.

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The Impact of Gelatin on the Pharmaceutical Characteristics of Fucoidan Microspheres with Posaconazole

Materials ◽

10.3390/ma14154087 ◽

2021 ◽

Vol 14 (15) ◽

pp. 4087

Author(s):

Marta Szekalska ◽

Aleksandra Citkowska ◽

Magdalena Wróblewska ◽

Katarzyna Winnicka

Keyword(s):

Antifungal Activity ◽

Drug Release ◽

Spray Drying ◽

Fungal Infections ◽

Drug Loading ◽

High Surface ◽

Vaginal Fluid ◽

Sustained Drug Release ◽

Candida Spp ◽

The Impact

Fungal infections and invasive mycoses, despite the continuous medicine progress, are an important globally therapeutic problem. Multicompartment dosage formulations (e.g., microparticles) ensure a short drug diffusion way and high surface area of drug release, which as a consequence can provide improvement of therapeutic efficiency compared to the traditional drug dosage forms. As fucoidan is promising component with wide biological activity per se, the aim of this study was to prepare fucospheres (fucoidan microparticles) and fucoidan/gelatin microparticles with posaconazole using the one-step spray-drying technique. Pharmaceutical properties of designed fucospheres and the impact of the gelatin addition on their characteristics were evaluated. An important stage of this research was in vitro evaluation of antifungal activity of developed microparticles using different Candida species. It was observed that gelatin presence in microparticles significantly improved swelling capacity and mucoadhesiveness, and provided a sustained POS release. Furthermore, it was shown that gelatin addition enhanced antifungal activity of microparticles against tested Candida spp. strains. Microparticles formulation GF6, prepared by the spray drying of 20% fucoidan, 5% gelatin and 10% Posaconazole, were characterized by optimal mucoadhesive properties, high drug loading and the most sustained drug release (after 8 h 65.34 ± 4.10% and 33.81 ± 5.58% of posaconazole was dissolved in simulated vaginal fluid pH 4.2 or 0.1 M HCl pH 1.2, respectively).

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Tailoring Atomoxetine Release Rate from DLP 3D-Printed Tablets Using Artificial Neural Networks: Influence of Tablet Thickness and Drug Loading

Molecules ◽

10.3390/molecules26010111 ◽

2020 ◽

Vol 26 (1) ◽

pp. 111

Author(s):

Gordana Stanojević ◽

Djordje Medarević ◽

Ivana Adamov ◽

Nikola Pešić ◽

Jovana Kovačević ◽

...

Keyword(s):

Ethylene Glycol ◽

Release Rate ◽

Drug Loading ◽

Prolonged Release ◽

Cylindrical Shape ◽

Poly Ethylene Glycol ◽

Scanning Calorimetry ◽

3D Printed ◽

Artificial Neural ◽

Poly Ethylene

Various three-dimensional printing (3DP) technologies have been investigated so far in relation to their potential to produce customizable medicines and medical devices. The aim of this study was to examine the possibility of tailoring drug release rates from immediate to prolonged release by varying the tablet thickness and the drug loading, as well as to develop artificial neural network (ANN) predictive models for atomoxetine (ATH) release rate from DLP 3D-printed tablets. Photoreactive mixtures were comprised of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 in a constant ratio of 3:1, water, photoinitiator and ATH as a model drug whose content was varied from 5% to 20% (w/w). Designed 3D models of cylindrical shape tablets were of constant diameter, but different thickness. A series of tablets with doses ranging from 2.06 mg to 37.48 mg, exhibiting immediate- and modified-release profiles were successfully fabricated, confirming the potential of this technology in manufacturing dosage forms on demand, with the possibility to adjust the dose and release behavior by varying drug loading and dimensions of tablets. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and microscopic analysis showed that ATH remained in a crystalline form in tablets, while FTIR spectroscopy confirmed that no interactions occurred between ATH and polymers.

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Eudragit S-100 coated sodium alginate microspheres of naproxen sodium: Formulation, optimization and in vitro evaluation / Alginatne mikrosfere naproksen natrija obložene Eudragitom S-100: Priprava, optimizacija i in vitro vrednovanje

Acta Pharmaceutica ◽

10.2478/v10007-012-0034-x ◽

2012 ◽

Vol 62 (4) ◽

pp. 529-545 ◽

Cited By ~ 23

Author(s):

Anuj Chawla ◽

Pooja Sharma ◽

Pravin Pawar

Keyword(s):

Drug Release ◽

Sodium Alginate ◽

Naproxen Sodium ◽

Drug Loading ◽

Size Analysis ◽

Scanning Calorimetry ◽

Sem Images ◽

S 100 ◽

Eudragit S 100

The aim of the study was to prepare site specific drug delivery of naproxen sodium using sodium alginate and Eudragit S-100 as a mucoadhesive and pH-sensitive polymer, respectively. Core microspheres of alginate were prepared by a modified emulsification method followed by cross-linking with CaCl2, which was further coated with the pH dependent polymer Eudragit S-100 (2.5 or 5 %) to prevent drug release in the upper gastrointestinal environment. Microspheres were characterized by FT-IR spectroscopy, X-ray diffraction, differential scanning calorimetry and evaluated by scanning electron microscopy, particle size analysis, drug loading efficiency, in vitro mucoadhesive time study and in vitro drug release study in different simulated gastric fluids. Stability studies of the optimized formulation were carried out for 6 months. SEM images revealed that the surface morphology was rough and smooth for core and coated microspheres, respectively. Core microspheres showed better mucoadhesion compared to coated microspheres when applied to the mucosal surface of freshly excised goat colon. The optimized batch of core microspheres and coated microspheres exhibited 98.42 ± 0.96 and 95.58 ± 0.74 % drug release, respectively. Drug release from all sodium alginate microsphere formulations followed Higuchi kinetics. Moreover, drug release from Eudragit S-100 coated microspheres followed the Korsmeyer-Peppas equation with a Fickian kinetics mechanism. Stability study suggested that the degradation rate constant of microspheres was minimal, indicating 2 years shelf life of the formulation.

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

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.393-395.119 ◽

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.

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Biological Properties of Ti-Nb-Zr-O Nanostructures Grown on Ti35Nb5Zr Alloy

Journal of Nanomaterials ◽

10.1155/2012/834042 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Zhaohui Li ◽

Congqin Ning ◽

Dongyan Ding ◽

Hegang Liu ◽

Lin Huang

Keyword(s):

Stem Cell ◽

Drug Release ◽

Drug Loading ◽

Biological Properties ◽

Prolonged Release ◽

Apatite Formation ◽

Release Process ◽

Oxide Nanostructures ◽

Implant Alloys

Surface modification of low modulus implant alloys with oxide nanostructures is one of the important ways to achieve favorable biological behaviors. In the present work, amorphous Ti-Nb-Zr-O nanostructures were grown on a peak-aged Ti35Nb5Zr alloy through anodization. Biological properties of the Ti-Nb-Zr-O nanostructures were investigated throughin vitrobioactivity testings, stem cell interactions, and drug release experiments. The Ti-Nb-Zr-O nanostructures demonstrated a good capability of inducing apatite formation after immersion in simulated body fluids (SBFs). Drug delivery experiment based on gentamicin and the Ti-Nb-Zr-O nanostructures indicated that a high drug loading content could result in a prolonged release process and a higher quantity of drug residues in the oxide nanostructures after drug release. Quick stem cell adhesion and spreading, as well as fast formation of extracellular matrix materials on the surfaces of the Ti-Nb-Zr-O nanostructures, were found. These findings make it possible to further explore the biomedical applications of the Ti-Nb-Zr-O nanostructure modified alloys especially clinical operation of orthopaedics by utilizing the nanostructures-based drug-release system.

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Unravelling the Miscibility of Poly(2-oxazoline)s: A Novel Polymer Class for the Formulation of Amorphous Solid Dispersions

Molecules ◽

10.3390/molecules25163587 ◽

2020 ◽

Vol 25 (16) ◽

pp. 3587

Author(s):

Melissa Everaerts ◽

Ali Tigrine ◽

Victor R. de la Rosa ◽

Richard Hoogenboom ◽

Peter Adriaensens ◽

...

Keyword(s):

Body Temperature ◽

Drug Release ◽

Solid Dispersions ◽

Amorphous Solid ◽

Water Soluble ◽

Resonance Spectroscopy ◽

Scanning Calorimetry ◽

Amorphous Solid Dispersions ◽

Soluble Polymer ◽

Water Soluble Polymer

Water-soluble polymers are still the most popular carrier for the preparation of amorphous solid dispersions (ASDs). The advantage of this type of carrier is the fast drug release upon dissolution of the water-soluble polymer and thus the initial high degree of supersaturation of the poorly soluble drug. Nevertheless, the risk for precipitation due to fast drug release is a phenomenon that is frequently observed. In this work, we present an alternative carrier system for ASDs where a water-soluble and water-insoluble carrier are combined to delay the drug release and thus prevent this onset of precipitation. Poly(2-alkyl-2-oxazoline)s were selected as a polymer platform since the solution properties of this polymer class depend on the length of the alkyl sidechain. Poly(2-ethyl-2-oxazoline) (PEtOx) behaves as a water-soluble polymer at body temperature, while poly(2-n-propyl-2-oxazoline) (PPrOx) and poly(2-sec-butyl-2-oxazoline) (PsecBuOx) are insoluble at body temperature. Since little was known about the polymer’s miscibility behaviour and especially on how the presence of a poorly-water soluble drug impacted their miscibility, a preformulation study was performed. Formulations were investigated with X-ray powder diffraction, differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance spectroscopy. PEtOx/PPrOx appeared to form an immiscible blend based on DSC and this was even more pronounced after heating. The six drugs that were tested in this work did not show any preference for one of the two phases. PEtOx/PsecBuOx on the other hand appeared to be miscible forming a homogeneous blend between the two polymers and the drugs.

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Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

Polymers ◽

10.3390/polym12091872 ◽

2020 ◽

Vol 12 (9) ◽

pp. 1872 ◽

Cited By ~ 4

Author(s):

Rishi Thakkar ◽

Amit Raviraj Pillai ◽

Jiaxiang Zhang ◽

Yu Zhang ◽

Vineet Kulkarni ◽

...

Keyword(s):

Drug Release ◽

Hydroxypropyl Methylcellulose ◽

Amorphous State ◽

Dosage Forms ◽

Water Soluble ◽

Patient Specific ◽

3 Dimensional ◽

Fused Deposition ◽

3D Printed ◽

The Impact

This research demonstrates the use of fill density as an effective tool for controlling the drug release without changing the formulation composition. The merger of hot-melt extrusion (HME) with fused deposition modeling (FDM)-based 3-dimensional (3-D) printing processes over the last decade has directed pharmaceutical research towards the possibility of printing personalized medication. One key aspect of printing patient-specific dosage forms is controlling the release dynamics based on the patient’s needs. The purpose of this research was to understand the impact of fill density and interrelate it with the release of a poorly water-soluble, weakly acidic, active pharmaceutical ingredient (API) from a hydroxypropyl methylcellulose acetate succinate (HPMC-AS) matrix, both mathematically and experimentally. Amorphous solid dispersions (ASDs) of ibuprofen with three grades of AquaSolveTM HPMC-AS (HG, MG, and LG) were developed using an HME process and evaluated using solid-state characterization techniques. Differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), and polarized light microscopy (PLM) confirmed the amorphous state of the drug in both polymeric filaments and 3D printed tablets. The suitability of the manufactured filaments for FDM processes was investigated using texture analysis (TA) which showed robust mechanical properties of the developed filament compositions. Using FDM, tablets with different fill densities (20–80%) and identical dimensions were printed for each polymer. In vitro pH shift dissolution studies revealed that the fill density has a significant impact (F(11, 24) = 15,271.147, p < 0.0001) and a strong negative correlation (r > −0.99; p < 0.0001) with the release performance, where 20% infill demonstrated the fastest and most complete release, whereas 80% infill depicted a more controlled release. The results obtained from this research can be used to develop a robust formulation strategy to control the drug release from 3D printed dosage forms as a function of fill density.

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