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

Molecules ◽  
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.

scholarly journals Influence of Carbamazepine Dihydrate on the Preparation of Amorphous Solid Dispersions by Hot Melt Extrusion

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 379 ◽  
Author(s):  
Xiangyu Ma ◽  
Felix Müller ◽  
Siyuan Huang ◽  
Michael Lowinger ◽  
Xu Liu ◽  
...  
Keyword(s):  
Energy State ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Hot Melt Extrusion ◽  
Water Soluble ◽  
Melt Extrusion ◽  
Amorphous Solid Dispersions ◽  
Water Soluble Drugs ◽  
The Impact ◽  
Hot Melt

Amorphous solid dispersions (ASDs) are commonly used in the pharmaceutical industry to improve the dissolution and bioavailability of poorly water-soluble drugs. Hot melt extrusion (HME) has been employed to prepare ASD based products. However, due to the narrow processing window of HME, ASDs are normally obtained with high processing temperatures and mechanical stress. Interestingly, one-third of pharmaceutical compounds reportedly exist in hydrate forms. In this study, we selected carbamazepine (CBZ) dihydrate to investigate its solid-state changes during the dehydration process and the impact of the dehydration on the preparation of CBZ ASDs using a Leistritz micro-18 extruder. Various characterization techniques were used to study the dehydration kinetics of CBZ dihydrate under different conditions. We designed the extrusion runs and demonstrated that: 1) the dehydration of CBZ dihydrate resulted in a disordered state of the drug molecule; 2) the resulted higher energy state CBZ facilitated the drug solubilization and mixing with the polymer matrix during the HME process, which significantly decreased the required extrusion temperature from 140 to 60 °C for CBZ ASDs manufacturing compared to directly processing anhydrous crystalline CBZ. This work illustrated that the proper utilization of drug hydrates can significantly improve the processability of HME for preparing ASDs.

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

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 529 ◽  
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.

scholarly journals Compression-Induced Phase Transitions of Bicalutamide

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 438 ◽  
Author(s):  
Joanna Szafraniec-Szczęsny ◽  
Agata Antosik-Rogóż ◽  
Justyna Knapik-Kowalczuk ◽  
Mateusz Kurek ◽  
Ewa Szefer ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Active Pharmaceutical Ingredient ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
X Ray ◽  
High Propensity ◽  
Poorly Soluble ◽  
Amorphous Drug

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

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

2008 ◽  
Vol 58 (1) ◽  
pp. 99-110 ◽  
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.

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

2015 ◽  
Vol 483 (1-2) ◽  
pp. 256-267 ◽  
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

scholarly journals A Review on Solid Dispersion and Carriers Used Therein for Solubility Enhancement of Poorly Water Soluble Drugs

2020 ◽  
Vol 10 (3) ◽  
pp. 359-369
Author(s):  
Avinash Ramrao Tekade ◽  
Jyoti Narayan Yadav
Keyword(s):  
Recent Trend ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Immediate Release ◽  
Water Soluble ◽  
Amorphous Solid Dispersions ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Enhanced Properties

A large number of hydrophilic and hydrophobic carriers in pharmaceutical excipients are available today which are used for formulation of solid dispersions. Depending on nature of carriers the immediate release solid dispersions and/or controlled release solid dispersions can be formulated. Initially crystalline carriers were used which are transformed into amorphous solid dispersions with enhanced properties. The carriers used previously were mostly synthetic one. Recent trend towards the use of natural carriers have replaced the use of synthetic carriers. This review is the overview of various synthetic, natural, semisynthetic, modified natural hydrophilic carriers used for formulation of solid dispersions.

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