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).

AMORPHOUS SOLID DISPERSIONS OF PIOGLITAZONE HYDROCHLORIDE USING CREMOPHOR RH 40 AND POLOXAMER 188: IN VITRO AND IN VIVO EVALUATION

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (01) ◽  
pp. 45-55
Author(s):  
R. P Swain ◽  
B. B Subudhi ◽  
Keyword(s):  
Solid Dispersions ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Amorphous Solid Dispersions ◽  
In Vivo Evaluation ◽  
In Vivo Test ◽  
Water Soluble Drug

The study was aimed to improve dissolution and bioavailability of developed stable amorphous solid dispersions (SDs) of pioglitazone hydrochloride (PGH), a poorly water soluble drug. TGA showed compatibility with the polymers. The significant change in melting pattern of the PGH observed in the DSC thermograms supported by XRD patterns and SEM indicated change from crystalline to amorphous state. Prevention of recrystallization during storage suggested stability of formulation. Cremophor RH 40 based SD (solvent method) remarkably increased the dissolution within 15 min and was supported by dissolution parameters (Q15, IDR, RDR, % DE, f1, f2). In vivo test showed significantly (p < 0.05) higher AUC0-t and Cmax, which were about 4.46 and 4.84 times that of pure drug, respectively. Cremophor RH 40 was found to be a suitable carrier for SM for preparation of SDs of PH as evident from increased dissolution and bioavailability.

scholarly journals Micro-Injection Moulding of Poly(vinylpyrrolidone-vinyl acetate) Binary and Ternary Amorphous Solid Dispersions

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 240
Author(s):  
Romina Pezzoli ◽  
Michael Hopkins Jnr ◽  
Guillaume Direur ◽  
Noel Gately ◽  
John G. Lyons ◽  
...  
Keyword(s):  
Vinyl Acetate ◽  
Injection Moulding ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Dissolution Profile ◽  
Amorphous Solid Dispersions ◽  
Micro Injection Moulding

Micro-injection moulding (µIM) was used for the production of enteric tablets of plasticised and unplasticised solid dispersions of poly(vinylpyrrolidone-vinyl acetate) (PVPVA), and the effect of the mechanical and thermal treatment on the properties of the dispersions was investigated. The physical state of the systems showed to be unaltered by the µIM step, maintaining the drug in the amorphous state. The dissolution profile of the tablets showed a slower dissolution rate due to the lower surface to volume ratio compared to the extruded strands. The lack of solubility of the doses in the acidic medium as a consequence of the acidity of indomethacin (IND) was observed. However, in neutral pH the drug dissolution showed slower rates without affecting the dissolution extent, showing a potential application for the development of controlled release doses. Overall, the production of tablets of amorphous solid dispersions (ASD), coupling hot-melt extrusion (HME) and µIM, proved to be a successful approach towards a continuous automated manufacturing process to improve the aqueous solubility of poorly water-soluble 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 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.

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