scholarly journals Drug Amorphous Solid Dispersions Based on Poly(vinyl Alcohol): Evaluating the Effect of Poly(propylene Succinate) as Plasticizer

Polymers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 2922
Author(s):  
Afroditi Kapourani ◽  
Artemis Palamidi ◽  
Konstantinos N. Kontogiannopoulos ◽  
Nikolaos D. Bikiaris ◽  
Panagiotis Barmpalexis
Keyword(s):  
Melting Temperature ◽  
Vinyl Alcohol ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Poly Vinyl Alcohol ◽  
Melt Mixing ◽  
Amorphous Solid Dispersions ◽  
Quench Cooling ◽  
Poly Propylene

Although significant actions have been taken towards the utilization of poly(vinyl alcohol) (PVA) in the preparation of drug amorphous solid dispersions (ASDs) using fusion-based techniques (such as melt-quench cooling and hot-melt extrusion), several drawbacks regarding its rather high melting temperature and its thermal degradation profile make the use of the polymer extremely challenging. This is especially important when the active pharmaceutical ingredient (API) has a lower melting temperature (than PVA) or when it is thermally labile. In this vein, a previous study showed that newly synthesized polyester-based plasticizers may improve the processability and the thermal properties of PVA. However, the effects of such polyester-based plasticizers on the drug’s physicochemical and pharmaco-technical properties are yet unknown. Hence, the aim of the present study is to extend our previous findings and evaluate the use of poly(propylene succinate) (PPSu, i.e., the most promising plasticizer in regard to PVA) in the preparation of drug-loaded PVA-based ASDs. Dronedarone (DRN), a poorly water-soluble API, was selected as a model drug, and drug ASDs (using either neat PVA or PVA-PPSu) were prepared using the melt-mixing/quench cooling approach at low melting temperatures (i.e., 170 °C). DSC and pXRD analysis showed that a portion of the API remained crystalline in the ASDs prepared only with the use of neat PVA, while the samples having PPSu as a plasticizer were completely amorphous. Further evaluation with ATR-FTIR spectroscopy revealed the formation of significant intermolecular interactions between the API and the PVA-PPSu matrix, which could explain the system’s physical stability during storage. Finally, dissolution studies, conducted under nonsink conditions, revealed that the use of PVA-PPSu is able to maintain DRN’s sustained supersaturation for up to 8 h.

Effect of Cobalt Stearate and Vegetable Oil on Uv and Biodegradation of Linear Low-Density Poly(Ethylene)-Poly(Vinyl Alcohol) Blends

2011 ◽  
Vol 2 (4) ◽  
pp. 131-148 ◽  
Author(s):  
Francis Vidya ◽  
Subin S. Raghul ◽  
Sarita G Bhat ◽  
Eby Thomas Thachil
Keyword(s):  
Vegetable Oil ◽  
Vinyl Alcohol ◽  
Water Soluble ◽  
Poly Vinyl Alcohol ◽  
Low Density ◽  
Compression Moulding ◽  
Melt Mixing ◽  
Degradation Behaviour ◽  
Moulding Process ◽  
Poly Ethylene

The main objective of this study was to enhance the rate of UV and biodegradation of polyethylene by incorporating biodegradable materials and prooxidants. Prooxidants such as transition metal complexes are capable of initiating photooxidation and polymer chain cleavage, rendering the product more susceptible to biodegradation. In this work, the effect of (1) a metallic photoinitiator, cobalt stearate, and (2) different combinations of cobalt stearate and vegetable oil on the photooxidative degradation of linear low-density poly(ethylene)-poly(vinyl alcohol) (LLDPE/PVA) blend films has been investigated. For this, film-grade LLDPE was blended with different proportions of PVA. PVA is widely used in the industrial field, and recently it has attracted increasing attention as a water-soluble biodegradable polymer. Cobalt stearate and vegetable oil were added to the blends as prooxidants. The blends were prepared by melt mixing in a Thermo HAAKE Polylab system. Thin films containing these additives were prepared by a subsequent compression moulding process. The effect of UV exposure on LLDPE/PVA films in the presence as well as absence of these additives was investigated. Tensile properties, FTIR spectra, and scanning electron microscopy (SEM) were employed to investigate the degradation behaviour. It was found

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 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 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.

scholarly journals Continuous Formulation Approaches of Amorphous Solid Dispersions: Significance of Powder Flow Properties and Feeding Performance

Pharmaceutics ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 654 ◽  
Author(s):  
Edina Szabó ◽  
Balázs Démuth ◽  
Dorián László Galata ◽  
Panna Vass ◽  
Edit Hirsch ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Scale Up ◽  
Amorphous Solid ◽  
Downstream Processing ◽  
Water Soluble ◽  
Content Uniformity ◽  
Amorphous Solid Dispersions ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble

Preparation and formulation of amorphous solid dispersions (ASDs) are becoming more and more popular in the pharmaceutical field because the dissolution of poorly water-soluble drugs can be effectively improved this way, which can lead to increased bioavailability in many cases. During downstream processing of ASDs, technologists need to keep in mind both traditional challenges and the newest trends. In the last decade, the pharmaceutical industry began to display considerable interest in continuous processing, which can be explained with their potential advantages such as smaller footprint, easier scale-up, and more consistent product, better quality and quality assurance. Continuous downstream processing of drug-loaded ASDs opens new ways for automatic operation. Therefore, the formulation of poorly water-soluble drugs may be more effective and safe. However, developments can be challenging due to the poor flowability and feeding properties of ASDs. Consequently, this review pays special attention to these characteristics since the feeding of the components greatly influences the content uniformity in the final dosage form. The main purpose of this paper is to summarize the most important steps of the possible ASD-based continuous downstream processes in order to give a clear overview of current course lines and future perspectives.

scholarly journals Bioavailability Improvement of Carbamazepine via Oral Administration of Modified-Release Amorphous Solid Dispersions in Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1023
Author(s):  
Houli Li ◽  
Meimei Zhang ◽  
Lilong Xiong ◽  
Weiyi Feng ◽  
Robert O. Williams
Keyword(s):  
Controlled Release ◽  
Oral Absorption ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Pharmacokinetic Studies ◽  
Modified Release ◽  
Capsule Formulation ◽  
Amorphous Solid Dispersions

The purpose of this study was to improve the bioavailability of carbamazepine (CBZ), a poorly water-soluble antiepileptic drug, via modified-release amorphous solid dispersions (mr-ASD) by a thin film freezing (TFF) process. Three types of CBZ-mr-ASD with immediate-, delayed-, and controlled-release properties were successfully prepared with HPMC E3 (hydrophilic), L100-55 (enteric), and cellulose acetate (CA, lipophilic), defined as CBZ-ir-ASD, CBZ-dr-ASD, and CBZ-cr-ASD, respectively. A dry granulation method was used to prepare CBZ-mr-ASD capsule formulations. Various characterization techniques were applied to evaluate the physicochemical properties of CBZ-mr-ASD and the related capsules. The drug remained in an amorphous state when encapsulated within CBZ-mr-ASD, and the capsule formulation progress did not affect the performance of the dispersions. In dissolution tests, the preparations and the corresponding dosage forms similarly showed typical immediate-, delayed-, and controlled-release properties depending on the solubility of the polymers. Moreover, single-dose 24 h pharmacokinetic studies in rats indicated that CBZ-mr-ASD significantly enhanced the oral absorption of CBZ compared to that of crude CBZ. Increased oral absorption of CBZ was observed, especially in the CBZ-dr-ASD formulation, which showed a better pharmacokinetic profile than that of crude CBZ with 2.63- and 3.17-fold improved bioavailability of the drug and its main active metabolite carbamazepine 10,11-epoxide (CBZ-E).

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