The aim of this book is to provide a brief but comprehensive overview on the issue of drug bioavailability improvement by preparation of a perspective dosage form – liquisolid systems. The introduction chapter about drug solubility and bioavailability is followed by a description of the general methods which could be used to improve drug bioavailability using approaches of chemistry, physical modification, and primarily pharmaceutical technology. Benefits and practical use of each method are documented by examples.
The main part of the book is aimed at characterization and description of liquisolid systems (LSS) – perspective dosage form for bioavailability improvement. Elementary principles of LSS formulation are described in detail, e.g. how to perform a preformulation study; how to choose the correct type and amount of excipients; how to evaluate the dosage forms, etc. All the above mentioned principles are documented with practical examples.
The book could be used as a textbook for students of natural, medical and pharmaceutical sciences as well as by researchers in this field or industrial area. Contemporary pharmacotherapy is characterized by the increasing amount of active substances that are only poorly soluble in water. This may lead to the limitation of their systemic absorption on oral administration which is closely related to the bioavailability. This category is estimated to include more than forty percent of active substances that are in general use.
So far, this poor aqueous solubility has been improved by physical or chemical modification of the active substance. In general, such changes are very expensive and troublesome, often leading to problems in stability, marketing authorization process, or administration comfort of the particular drug. This is one of the reasons why modern pharmaceutical technology has focused on those dosage forms that can increase the bioavailability of some active substances while maintaining suitable stability and administration comfort. Several processes that improve solubility, respectively bioavailability have been described and published. These include micronization, nanocrystals, and formulation of solid dispersions. Only recently, a novel trend has appeared – to take advantage of good solubility of active substances in chosen solvents, that is, to use the active substances in a liquid phase.
Inhaltsverzeichnis (Table of Contents)
- BIOAVAILABILITY OF ACTIVE PHARMACEUTICAL INGREDIENTS
- Bioavailability...
- Physical-chemical properties of active substances...
- Solubility
- Acidobasic properties.
- Partition coefficient
- Size and shape of the molecule
- pH in stomach and intestine
- Binding to plasma proteins.
- Factors within the organism.
- Gastric emptying and intestinal motility
- Impact of enzymes
- Drug metabolism and first-pass effect..
- Biorhythms.
- Intra- and interindividual variability.
- Dosage form.
- Food.....
- METHODS TO IMPROVE BIOAVAILABILITY.
- Chemical modification of active substance.
- Salts
- Hydrates
- Cocrystals.
- Prodrugs
- Chelation
- Physical methods.
- Amorphism and crystal polymorphism.
- Controlled crystallization.
- Sono-crystallization..
- Crystallization from supracritical fluids.
- Freeze drying..
- Spray drying
- Particle size reduction of active substances
- Dry milling
- Freeze milling..
- Wet milling .\n
- Technological means…..........\n
- Mediated dissolution
- Increasing of wettability.
- Micellar solubilization .....
- Cosolvents
- Hydrotropes.
- Cyclodextrin complexes..
- pH adjustment.
- Solid dispersions
- Interactive powder mixtures.
- Microgranulation .......
- Self-emulsifying systems
- Liquisolid systems..\n
- Mediated dissolution
- Chemical modification of active substance.
- LIQUISOLID SYSTEMS
- History………………………………………….
- Advantages..
- Disadvantages...
- Technology..\n
- Preformulation testing.
- Flowable liquid retention potential
- Optimal load factor...
- Liquisolid compressibility test.\n
- Excipients...........
- Solvents.
- Propylene glycol
- Liquid polyethylene glycols
- Polysorbates.....
- Glycerol
- Poloxamers
- Polyoxyethylated castor oil ........
- Polyoxyethylated hydrogenated castor oil...\n
- Propylene glycol caprylate
- Macrogol-15-hydroxystearate
- Polyvinyl acetate......
- Conventional carriers
- Modified starch.
- Lactose...........
- Microcrystalline cellulose...........
- Anhydrous dibasic calcium phosphate
- Mesoporous silicates.......
- Magnesium aluminometasilicates...\n
- Solvents.
- Preformulation testing.
Zielsetzung und Themenschwerpunkte (Objectives and Key Themes)
This book aims to provide a comprehensive overview of drug bioavailability improvement through the utilization of liquisolid systems, a promising dosage form. The book covers various methods for enhancing drug bioavailability, including chemical and physical modifications, and pharmaceutical technology approaches. It delves into the specific characteristics and principles of liquisolid systems, encompassing preformulation studies, excipient selection, and dosage form evaluation.
- Drug solubility and bioavailability improvement
- Liquisolid systems as a perspective dosage form
- Preformulation studies and excipient selection for liquisolid systems
- Evaluation techniques for liquisolid dosage forms
- Practical examples and applications of liquisolid systems
Zusammenfassung der Kapitel (Chapter Summaries)
The book begins by introducing the concept of drug bioavailability and its importance in pharmacotherapy. Chapter 1 explores the physical-chemical properties of active substances that influence their bioavailability, including solubility, acid-base properties, partition coefficient, molecular size and shape, and factors related to the organism's absorption process, such as gastric emptying, enzyme activity, and metabolism. Chapter 2 delves into various methods used to enhance bioavailability, encompassing chemical modifications of active substances like salt formation, hydration, cocrystallization, and prodrug formation. It also explores physical methods such as controlled crystallization, freeze drying, and spray drying. Furthermore, it covers technological approaches including mediated dissolution, cyclodextrin complexes, pH adjustment, and solid dispersions.
Finally, the book focuses on the application of liquisolid systems for improving drug bioavailability. Chapter 3 presents a comprehensive description of these systems, including their history, advantages, disadvantages, and underlying technology. This chapter also covers preformulation testing, excipient selection, and evaluation methods specific to liquisolid systems. This in-depth analysis of liquisolid systems provides valuable insights for researchers, pharmacists, and scientists working in drug development.
Schlüsselwörter (Keywords)
The core keywords and focus topics of this book revolve around enhancing drug bioavailability through the utilization of liquisolid systems. This encompasses key concepts such as solubility, bioavailability, pharmaceutical technology, preformulation studies, excipient selection, evaluation techniques, and the practical application of liquisolid systems as a dosage form. These concepts are central to the book's exploration of modern approaches to drug delivery and bioavailability optimization.
- Arbeit zitieren
- Dr. Jan Gajdziok (Autor:in), Barbora Vraníková (Autor:in), Klára Kostelanská (Autor:in), David Vetchý (Autor:in), Jan Muselík (Autor:in), Roman Goněc (Autor:in), 2018, Drug solubility and bioavailability improvement. Possible methods with emphasis on liquisolid systems formulation, München, GRIN Verlag, https://www.grin.com/document/442018
