The Effect of Molecular Properties on Active Ingredient Release from Electrospun Eudragit Fibers

The formation of nanoscale fibers from pH-sensitive polymers is a route which has been widely explored for targeted drug delivery. In particular, the Eudragit L100 and S100 families of polymers have received significant attention for this purpose. However, while in some cases it is shown that making drug-loaded Eudragit polymers effectively prevents drug release in low-pH media where the polymer is insoluble, this is not always the case, and other studies have reported significant amounts of drug release at acidic pHs. In this study, we sought to gain insight into the factors influencing the release of active ingredients from Eudragit S100 (ES100) fibers. A family of materials was prepared loaded with the model active ingredients (AIs) benzoic acid, 1-naphthoic acid, 1-naphthylamine, and 9-anthracene carboxylic acid. Analogous systems were prepared with an AI-loaded core and an ES100 sheath. The resultant fibers were smooth and cylindrical in the majority of cases, and X-ray diffraction and differential scanning calorimetry showed them to comprise amorphous solid dispersions. When AI release from the monolithic fibers was probed, it was found that there was significant release at pH 1 in all cases except with 9-anthracene carboxylic acid. Analysis of the results indicated that both the molecular weight of the AI and its acidity/basicity are important in controlling release, with lower molecular weight AIs and basic species released more quickly. The same release trends are seen with the core/shell fibers, but AI release at pH 1 is attenuated. The most significant change between the monolithic and core/shell systems was observed in the case of 1-naphthylamine. Mathematical equations were devised to connect molecular properties and AI release under acidic conditions.

Download Full-text

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.

Download Full-text

DEVELOPMENT AND CHARACTERIZATION OF NEVIRAPINE LOADED AMORPHOUS SOLID DISPERSIONS FOR SOLUBILITY ENHANCEMENT

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i18.34097 ◽

2019 ◽

pp. 176-182

Author(s):

GAGANDEEP SINGH ◽

NAVJOT SINGH ◽

RANDEEP KUMAR ◽

NEENA BEDI

Keyword(s):

Vitamin E ◽

Drug Release ◽

Solid Dispersions ◽

Amorphous Solid ◽

Glycol Succinate ◽

Scanning Calorimetry ◽

Compression Technique ◽

Vitamin E Tpgs ◽

Best Fitting

Objective: The present study entails the development of nevirapine (NVP)-loaded solid dispersions for improvement of solubility and in vitro profile. Methods: Solid dispersions were prepared through blending with a hydrophilic polymer and Vitamin E tocopherol polyethylene glycol succinate (TPGS) using the solvent evaporation method. The optimized formulations were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and morphological investigations by scanning electron microscopy. The optimized formulation was converted into fast dissolving tablets (FDTs) through direct compression technique and was characterized for pre- and post-compression parameters. Both amorphous dispersions and FDTs were evaluated for in vitro drug release. Results: NVP showed pH-dependent solubility in different pH media. Above 0.002% w/v Vitamin E TPGS, a linear relationship was observed between the NVP solubility and Vitamin E TPGS concentration. According to the study, the most suitable formulation was NVP:Vitamin E TPGS (1:0.75) in 30 ml solvent with a drug release of 82.96% in 2 h. The analysis of dissolution data of optimized formulation indicated the best fitting with the Higuchi model. FDTs exhibited faster drug release of about 50% in 5 min indicating desired attributes for the immediate dosage form. Conclusion: The present study vouches for better in vitro profile of NVP from solid dispersion based FDTs.

Download Full-text

Influence of Low-Molecular-Weight Excipients on the Phase Behavior of PVPVA64 Amorphous Solid Dispersions

Pharmaceutical Research ◽

10.1007/s11095-017-2316-y ◽

2018 ◽

Vol 35 (1) ◽

Cited By ~ 16

Author(s):

Kristin Lehmkemper ◽

Samuel O. Kyeremateng ◽

Matthias Degenhardt ◽

Gabriele Sadowski

Keyword(s):

Molecular Weight ◽

Phase Behavior ◽

Solid Dispersions ◽

Amorphous Solid ◽

Low Molecular Weight ◽

Amorphous Solid Dispersions

Download Full-text

Drug release mechanisms from amorphous solid dispersions

Journal of Controlled Release ◽

10.1016/j.jconrel.2015.06.027 ◽

2015 ◽

Vol 211 ◽

pp. 171 ◽

Cited By ~ 9

Author(s):

Kinam Park

Keyword(s):

Drug Release ◽

Solid Dispersions ◽

Amorphous Solid ◽

Amorphous Solid Dispersions ◽

Release Mechanisms

Download Full-text

Myth or Truth: The Glass Forming Ability Class III Drugs Will Always Form Single-Phase Homogenous Amorphous Solid Dispersion Formulations

Pharmaceutics ◽

10.3390/pharmaceutics11100529 ◽

2019 ◽

Vol 11 (10) ◽

pp. 529 ◽

Cited By ~ 4

Author(s):

Piyush Panini ◽

Massimiliano Rampazzo ◽

Abhishek Singh ◽

Filip Vanhoutte ◽

Guy Van den Mooter

Keyword(s):

Single Phase ◽

Solid Dispersions ◽

Amorphous Solid ◽

Glass Forming Ability ◽

Amorphous Solid Dispersion ◽

Class Iii ◽

Scanning Calorimetry ◽

Amorphous Solid Dispersions ◽

Modulated Differential Scanning Calorimetry ◽

Glass Forming

The physical stability of amorphous solid dispersions (ASD) of active pharmaceutical ingredients (APIs) of high glass forming ability (GFA class III) is generally expected to be high among the scientific community. In this study, the ASD of ten-selected class III APIs with the two polymers, PVPVA 64 and HPMC-E5, have been prepared by spray-drying, film-casting, and their amorphicity at T0 was investigated by modulated differential scanning calorimetry and powder X-ray diffraction. It was witnessed that only five out of ten APIs form good quality amorphous solid dispersions with no phase separation and zero crystalline content, immediately after the preparation and drying process. Hence, it was further established that the classification of an API as GFA class III does not guarantee the formulation of single phase amorphous solid dispersions.

Download Full-text

Compression-Induced Phase Transitions of Bicalutamide

Pharmaceutics ◽

10.3390/pharmaceutics12050438 ◽

2020 ◽

Vol 12 (5) ◽

pp. 438 ◽

Cited By ~ 1

Author(s):

Joanna Szafraniec-Szczęsny ◽

Agata Antosik-Rogóż ◽

Justyna Knapik-Kowalczuk ◽

Mateusz Kurek ◽

Ewa Szefer ◽

...

Keyword(s):

Solid Dispersions ◽

Amorphous Solid ◽

Active Pharmaceutical Ingredient ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Amorphous Solid Dispersions ◽

X Ray ◽

High Propensity ◽

Poorly Soluble ◽

Amorphous Drug

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

Download Full-text

Solid dispersion of meloxicam: Factorially designed dosage form for geriatric population

Acta Pharmaceutica ◽

10.2478/v10007-007-0048-y ◽

2008 ◽

Vol 58 (1) ◽

pp. 99-110 ◽

Cited By ~ 17

Author(s):

Deepa Pathak ◽

Sunita Dahiya ◽

Kamla Pathak

Keyword(s):

Drug Release ◽

Solid Dispersion ◽

Dosage Form ◽

Solid Dispersions ◽

Methyl Cellulose ◽

Water Soluble ◽

Hydroxyethyl Cellulose ◽

Scanning Calorimetry ◽

Geriatric Population ◽

Peg 4000

Solid dispersion of meloxicam: Factorially designed dosage form for geriatric populationThe objective of the present work was to improve the dissolution properties of the poorly water-soluble drug meloxicam by preparing solid dispersions with hydroxyethyl cellulose (HEC), mannitol and polyethylene glycol (PEG) 4000 and to develop a dosage form for geriatric population. Differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy and scanning electron microscopy were used to investigate the solid-state physical structure of the prepared solid dispersions. Higher invitrodissolution of solid dispersions was recorded compared to their corresponding physical mixtures and the pure drug. PEG 4000 in 1: 9 drug to carrier ratio exhibited the highest drug release (100.2%), followed by mannitol (98.2%) and HEC (89.5%) in the same ratio. Meloxicam-PEG 4000 solid dispersion was formulated into suspension and optimization was carried out by 23factorial design. Formulations containing higher levels of methyl cellulose and higher levels of either sodium citrate or Tween 80 exhibited the highest drug release.

Download Full-text

Identifying the mechanisms of drug release from amorphous solid dispersions using MRI and ATR-FTIR spectroscopic imaging

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2015.02.035 ◽

2015 ◽

Vol 483 (1-2) ◽

pp. 256-267 ◽

Cited By ~ 33

Author(s):

Kateřina Punčochová ◽

Andrew V. Ewing ◽

Michaela Gajdošová ◽

Nina Sarvašová ◽

Sergei G. Kazarian ◽

...

Keyword(s):

Drug Release ◽

Solid Dispersions ◽

Spectroscopic Imaging ◽

Amorphous Solid ◽

Amorphous Solid Dispersions

Download Full-text

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

Pharmaceutics ◽

10.3390/pharmaceutics12060541 ◽

2020 ◽

Vol 12 (6) ◽

pp. 541 ◽

Cited By ~ 3

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.

Download Full-text