Solid Dispersions with Anionic EUDRAGIT&[reg] Polymers Using Spray Drying Technique to Increase the Solubility of Poorly Soluble Drugs

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.

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ENHANCEMENT OF THE SOLUBILITY OF FAMOTIDINE SOLID DISPERSION USING NATURAL POLYMER BY SOLVENT EVAPORATION

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021v13i3.40934 ◽

2021 ◽

pp. 193-198

Author(s):

HUSSEIN K. ALKUFI ◽

ASMAA M. RASHID

Keyword(s):

Hyaluronic Acid ◽

Solid Dispersion ◽

Solid Dispersions ◽

Solvent Evaporation ◽

Water Soluble ◽

Poorly Soluble Drugs ◽

Natural Polymer ◽

Solubility Study ◽

Poorly Soluble ◽

Pure Drug

Objective: The aims of the study to enhance solubility and dissolution of famotidine using natural polymer. Solubility study of a drug is one of the contributing factors of its oral bioavailability. The formulation of poorly soluble drugs for oral delivery presents a challenge to the formulation technologists. Methods: The present study has shown that it is possible to raise the solubility for poorly soluble drugs like famotidine, by preparing solid dispersion using natural water-soluble polymer (xyloglucan and hyaluronic acid) as solubilizer through solvent evaporation method. Physical mixture and solid dispersion of famotidine with xyloglucan (XG) or hyaluronic acid in a ratio of 1:1, 1:2, 1:3 were prepared. Solubility study, drug content, dissolution profile and compatibility study were performed for famotidine in solid dispersions XS1, XS2, XS3, HS4, HS5, HS6 as well as in physical mixtures at a ratio 1:1 for both polymer (XG and hyaluronic acid). Results: It was observed that solid dispersions of each drugs showed an increase in dissolution rate in comparison with its pure drug in the ratio of 1:1 (Drug: carrier). It can be concluded that with the care and proper use of xyloglucan, the solubility of drugs poorly soluble can be improved. The prepared solid dispersion showed improvement of drug solubility in all prepared formulas. The best result was obtained with formula XS1 (famotidine: xyloglucan at ratio 1:1) that showed 26 fold increase in solubility compared to the solubility of pure drug. Conclusion: The natural solid dispersion, increased wettability and reduced crystallinity of the drug which leads to improving solubility and dissolution.

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Spray drying of poorly soluble drugs from aqueous arginine solution

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2017.09.015 ◽

2017 ◽

Vol 532 (1) ◽

pp. 289-298 ◽

Cited By ~ 13

Author(s):

Rami Ojarinta ◽

Louise Lerminiaux ◽

Riikka Laitinen

Keyword(s):

Spray Drying ◽

Poorly Soluble Drugs ◽

Poorly Soluble

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Comparative study of the potential of poly(2-ethyl-2-oxazoline) as carrier in the formulation of amorphous solid dispersions of poorly soluble drugs

European Journal of Pharmaceutics and Biopharmaceutics ◽

10.1016/j.ejpb.2019.09.005 ◽

2019 ◽

Vol 144 ◽

pp. 79-90 ◽

Cited By ~ 6

Author(s):

Eline Boel ◽

Annelies Smeets ◽

Maarten Vergaelen ◽

Victor R. De la Rosa ◽

Richard Hoogenboom ◽

...

Keyword(s):

Comparative Study ◽

Solid Dispersions ◽

Amorphous Solid ◽

Poorly Soluble Drugs ◽

Amorphous Solid Dispersions ◽

Poorly Soluble

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Microspherical Particles of Solid Dispersion of Polyvinylpyrrolidone K29-32 for Inhalation Administration

BioMed Research International ◽

10.1155/2018/2412156 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

L. S. Usmanova ◽

M. A. Ziganshin ◽

I. T. Rakipov ◽

N. M. Lyadov ◽

A. E. Klimovitskii ◽

...

Keyword(s):

Spray Drying ◽

Solid Dispersions ◽

Amorphous State ◽

Optimal Size ◽

Drying Process ◽

Promising Alternative ◽

Poorly Soluble ◽

Model Drug ◽

Pharmaceutical Properties ◽

Inhalation Administration

Inhalation administration is a promising alternative to the invasive drug delivery methods. The particle size required for ideal drug aerosol preparation is between 1 and 3 μm. The application of microspherical particles of solid dispersions enhances bioavailability of poorly soluble drugs due to the solubilization. In the present work, the spray drying process of the production of microspherical particles of solid dispersions of polyvinylpyrrolidone K29-32 with model hydrophobic drug, phenacetin, was optimized using the results of DSC, PXRD, and viscometry. The diameter of the obtained particles is within 1–3 μm range. The Gibbs energy of dissolution in water was shown to be negative for the mixture with polymer/phenacetin mass ratio 5 : 1. We have demonstrated that the optimal size distribution for the inhalation administration is obtained for microspherical particles produced using spray caps with 7.0 μm hole size. The dissolution rates of phenacetin from the produced microspherical particles were faster than that of drug powder. As evidenced by powder X-ray diffraction data, phenacetin stayed in amorphous state for 4 months in microspherical particles of solid dispersions. According to the obtained results, strategic application of the spray drying process could be beneficial for the improvement of the pharmaceutical properties of model drug, phenacetin.

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Evaluation of Inutec SP1 as a new carrier in the formulation of solid dispersions for poorly soluble drugs

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2006.02.025 ◽

2006 ◽

Vol 316 (1-2) ◽

pp. 1-6 ◽

Cited By ~ 57

Author(s):

Guy Van den Mooter ◽

Ilse Weuts ◽

Thomas De Ridder ◽

Norbert Blaton

Keyword(s):

Solid Dispersions ◽

Poorly Soluble Drugs ◽

Poorly Soluble

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Encapsulation of Pharmaceutical and Nutraceutical Active Ingredients Using Electrospinning Processes

Nanomaterials ◽

10.3390/nano11081968 ◽

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.

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

Current Nanomedicine ◽

10.2174/2468187309666190314152451 ◽

2019 ◽

Vol 9 (3) ◽

pp. 184-197 ◽

Cited By ~ 3

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.

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