Polymeric Nanomicelles of Soluplus® as a Strategy for Enhancing the Solubility, Bioavailability and Efficacy of Poorly Soluble Active Compounds

2019 ◽  
Vol 9 (3) ◽  
pp. 184-197 ◽  
Author(s):  
Rosario Pignatello ◽  
Roberta Corsaro
Keyword(s):  
Polyvinyl Acetate ◽  
Solid Dispersions ◽  
Aqueous Media ◽  
Physical Stability ◽  
Small Diameter ◽  
Amorphous Solid ◽  
Poorly Soluble Drugs ◽  
Insoluble Drugs ◽  
Poorly Soluble

: Soluplus® is a commercially available graft amphipathic copolymer consisting of polyvinyl caprolactam, polyvinyl acetate, and polyethyleneglycol (13% PEG 6000/57% vinyl caprolactam/30% vinyl acetate). Among the various applications of this solubilizer excipient, produced by BASF, such as the production of amorphous solid dispersions of insoluble drugs, Soluplus® has shown to be able to form nano-sized micelles in water or other aqueous solutions, characterized by a very small diameter and an exceptionally narrow size distribution. These formulations allow to improve the solubility and physical stability in aqueous media of poorly soluble drugs. This review summarizes the recent data from literature on the methods of production and characterization of drugloaded nanomicelles based on Soluplus®, highlighting the potential fields of therapeutic application.

scholarly journals Relative Contributions of Solubility and Mobility to the Stability of Amorphous Solid Dispersions of Poorly Soluble Drugs: A Molecular Dynamics Simulation Study

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 101 ◽  
Author(s):  
Michael Brunsteiner ◽  
Johannes Khinast ◽  
Amrit Paudel
Keyword(s):  
Molecular Dynamics ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Dynamics Simulation ◽  
Limiting Factor ◽  
Poorly Soluble Drugs ◽  
Formulation Development ◽  
Amorphous Solid Dispersions ◽  
Poorly Soluble

Amorphous solid dispersions are considered a promising formulation strategy for the oral delivery of poorly soluble drugs. The limiting factor for the applicability of this approach is the physical (in)stability of the amorphous phase in solid samples. Minimizing the risk of reduced shelf life for a new drug by establishing a suitable excipient/polymer-type from first principles would be desirable to accelerate formulation development. Here, we perform Molecular Dynamics simulations to determine properties of blends of eight different polymer–small molecule drug combinations for which stability data are available from a consistent set of literature data. We calculate thermodynamic factors (mixing energies) as well as mobilities (diffusion rates and roto-vibrational fluctuations). We find that either of the two factors, mobility and energetics, can determine the relative stability of the amorphous form for a given drug. Which factor is rate limiting depends on physico-chemical properties of the drug and the excipients/polymers. The methods outlined here can be readily employed for an in silico pre-screening of different excipients for a given drug to establish a qualitative ranking of the expected relative stabilities, thereby accelerating and streamlining formulation development.

scholarly journals Encapsulation of Pharmaceutical and Nutraceutical Active Ingredients Using Electrospinning Processes

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1968
Author(s):  
Mina Zare ◽  
Karolina Dziemidowicz ◽  
Gareth R. Williams ◽  
Seeram Ramakrishna
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Strong Electric Field ◽  
Solid Dispersions ◽  
Electrospun Nanofibers ◽  
Amorphous Solid ◽  
Delivery Systems ◽  
Poorly Soluble Drugs ◽  
Poorly Soluble ◽  
Biological And Medical Applications

Electrospinning is an inexpensive and powerful method that employs a polymer solution and strong electric field to produce nanofibers. These can be applied in diverse biological and medical applications. Due to their large surface area, controllable surface functionalization and properties, and typically high biocompatibility electrospun nanofibers are recognized as promising materials for the manufacturing of drug delivery systems. Electrospinning offers the potential to formulate poorly soluble drugs as amorphous solid dispersions to improve solubility, bioavailability and targeting of drug release. It is also a successful strategy for the encapsulation of nutraceuticals. This review aims to briefly discuss the concept of electrospinning and recent progress in manufacturing electrospun drug delivery systems. It will further consider in detail the encapsulation of nutraceuticals, particularly probiotics.

scholarly journals Relative Contributions of Solubility and Mobility to the Stability of Amorphous Solid Dispersions of Poorly Soluble Drugs: A Molecular Dynamics Simulation Study

2018 ◽  
Author(s):  
Michael Brunsteiner ◽  
Johannes Khinast ◽  
Amrit Paudel
Keyword(s):  
Molecular Dynamics ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Dynamics Simulation ◽  
Limiting Factor ◽  
Poorly Soluble Drugs ◽  
Formulation Development ◽  
Amorphous Solid Dispersions ◽  
Poorly Soluble

Amorphous solid dispersions are considered a promising formulation strategy for the oral delivery of poorly soluble drugs. The limiting factor for the applicability of this approach is the physical (in)stability of the amorphous phase in solid samples. Minimizing the risk of reduced shelf life for a new drug by establishing a suitable excipient/polymer-type from first principles would be desirable to accelerate formulation development. Here we perform Molecular Dynamics simulations to determine properties of blends of eight different polymer-small molecule drug combinations for which stability data is available from a consistent set of literature data. We calculate thermodynamic factors (mixing energies) as well as mobilities (diffusion rates and roto-vibrational fluctuations). We find that either of the two factors, mobility and energetics, can determine the relative stability of the amorphous form for a given drug. Which factor is rate limiting depends on physico-chemical properties of the drug and the excipients/polymers. The methods outlined here can be readily employed for an in-silico pre-screening of different excipients for a given drug to establish a qualitative ranking of the expected relative stabilities, thereby accelerating and streamlining formulation development.

scholarly journals Crystallization Tendency of Pharmaceutical Glasses: Relevance to Compound Properties, Impact of Formulation Process, and Implications for Design of Amorphous Solid Dispersions

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 202 ◽  
Author(s):  
Kohsaku Kawakami
Keyword(s):  
Solid Dispersions ◽  
Physical Stability ◽  
Amorphous Solid ◽  
Developmental Studies ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
Drug Molecules ◽  
Candidate Drug ◽  
Poorly Soluble ◽  
Crystallization Tendency

Amorphous solid dispersions (ASDs) are important formulation strategies for improving the dissolution process and oral bioavailability of poorly soluble drugs. Physical stability of a candidate drug must be clearly understood to design ASDs with superior properties. The crystallization tendency of small organics is frequently estimated by applying rapid cooling or a cooling/reheating cycle to their melt using differential scanning calorimetry. The crystallization tendency determined in this way does not directly correlate with the physical stability during isothermal storage, which is of great interest to pharmaceutical researchers. Nevertheless, it provides important insights into strategy for the formulation design and the crystallization mechanism of the drug molecules. The initiation time for isothermal crystallization can be explained using the ratio of the glass transition and storage temperatures (Tg/T). Although some formulation processes such as milling and compaction can enhance nucleation, the Tg/T ratio still works for roughly predicting the crystallization behavior. Thus, design of accelerated physical stability test may be possible for ASDs. The crystallization tendency during the formulation process and the supersaturation ability of ASDs may also be related to the crystallization tendency determined by thermal analysis. In this review, the assessment of the crystallization tendency of pharmaceutical glasses and its relevance to developmental studies of ASDs are discussed.

scholarly journals Solid Dispersion: Solubility Enhancement Technique of Poorly Water Soluble Drug

2020 ◽  
Vol 10 (1) ◽  
pp. 173-177 ◽  
Author(s):  
, Ikram ◽  
Kapil Kumar
Keyword(s):  
Solid Dispersion ◽  
Solid Dispersions ◽  
Water Soluble ◽  
Poorly Soluble Drugs ◽  
Water Soluble Drug ◽  
Poorly Soluble ◽  
Inert Carrier ◽  
Poorly Water Soluble ◽  
Poorly Water Soluble Drug

Solid dispersion is a technique which is widely and successfully applied to improve the solubility, dissolution rates and consequently the bioavailability of poorly soluble drugs. Dispersion of one or more active ingredients (hydrophobic) is done with an inert carrier (hydrophilic) at solid-state prepared by fusion method, solvent, and melting solvent method. In this review article, we have focused on the methods of preparation, advantages, disadvantages and characterization of the solid dispersions. Keywords: Solid dispersion; dissolution; solubility.

scholarly journals Spray-Dried Paracetamol/Polyvinylpyrrolidone Amorphous Solid Dispersions: Part I—Stability of Powders and Tablets

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1938
Author(s):  
Lena Ritters ◽  
Yuanyuan Tian ◽  
Stephan Reichl
Keyword(s):  
Solid Dispersions ◽  
Physical Stability ◽  
Amorphous Solid ◽  
Polymorphic Form ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
Pharmaceutical Ingredients ◽  
Poorly Soluble ◽  
The Stability ◽  
Spray Dried

The formulation of active pharmaceutical ingredients (APIs) in amorphous solid dispersions (ASDs) is a promising approach to improve the bioavailability of poorly soluble compounds. However, problems often arise in the production of tablets from ASDs regarding the compressibility and recrystallization of the API. In the present study, the preparation of spray-dried ASDs of paracetamol (PCM) and four different types of polyvinylpyrrolidone (PVP) and their further processing into tablets were investigated. The influence of PVP type on the glass transition temperature (Tg) and the physical stability of ASD powders were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). ASD powders with 10 to 30% PCM were stable for at least 48 weeks. PCM contents of 40 to 50% led to recrystallization of the amorphous PCM within a few days or weeks. ASD with PVP/vinyl acetate (VA) copolymer (PVP/VA) was the most unstable and tended to recrystallize in PCM polymorphic form II. This formulation was therefore used for tablet studies. The influence of compression force on recrystallization, crushing strength, and drug release was investigated. Even high compression forces did not affect the stability of the ASD. However, the ASD tablets led to slow release of the API.

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