Mohammad Alnaief

Aerogels

Aerogel the frozen smoke is a truly remarkable material. It is the lightest (lowest-density) solid known to exist and holds the top spot in 14 categories in the Guinness Book of World Records, including the best insulator and the lowest-density solid. Aerogel is composed of 99.8% air. Still it is not conventional foam, but is a special porous material with extreme porosity on the micron scale. It is composed of individual particles of only a few nanometers in size, which are linked in a three-dimensional network.

Aerogels can be synthesized from silicon oxide (silica aerogels) as well as from different organic and inorganic substances, for example titanium oxide, aluminium oxide, carbon, starch, alginate, chitosan, agar, pectin cellulose, etc.

These novel materials have many superior properties, such as a low thermal conductivity, refractive index and sound speed, along with a high surface area and thermal stability. Aerogels can be made with a density only three times larger than that of air. Aerogels have many applications in different fields of science and industry. One of the most fascinating applications is the insulation of space shuttles with aerogels, practiced by NASA (USA). Many scientific groups are currently working with aerogels, which is evident by the International Symposium on Aerogels, taking place every three years [ISA 1-6]. Both synthesis and innovative applications of aerogels are of great interest at the present time.
Being environmentally friendly and non-toxic, silica aerogels can be used in the pharmaceutical industry. Their large surface area and open pore structure make them an ideal potential carrier material.

Silica Aerogel Properties

• Density: 0.003 - 0.35 g/cm3
• Internal Surface Area: 600-1000 m2/g
• Open Pore Network
• Primary Particle Diameter: 2-5 nm
• Mean Pore Diameter: ~20 nm
• Non-toxic
• Nearly transparent; scatters blue light
• Thermal Tolerance: shrinkage begins at 500°C, melting point > 1000°C
• Dielectric Constant: ~1.1 F/m
• Refraction Index: 1.0-1.05
• Inherently brittle - easily shatters into dust
• Destroyed by contact with liquid
• Can be shattered by rapid pressure changes
• Non-flammable
• Can be machined into almost any shape
• No laceration hazard – aerogel’s particles are smooth and round

Production methods

The process in which aerogels are made can be explained in simplest terms by its creator, Steven S. Kistler, who proclaimed: “Obviously, if one wishes to produce an aerogel, he must replace the liquid with air by some means in which the surface of the liquid is never permitted to recede within the gel. If a liquid is held under pressure always greater than the vapour pressure, and the temperature is raised, it will be transformed at the critical temperature into a gas without two phases having been present at any time” (S. S. Kistler, J. Phys. Chem. 34, 52, 1932).
An aerogel is made by the so called “sol-gel process”. During this process, all necessary compounds are mixed with a solvent and undergo a chemical reaction producing highly cross-linked particles. The mixture is a liquid at the beginning of the reaction, and becomes more and more viscous as the reaction proceeds. When the reaction is finished, the solution loses its fluidity and the whole reacting mixture turns into a gel. This gel consists of a three-dimensional network filled with the solvent. During the special drying procedure (supercritical drying), the solvent is extracted from the gel body leaving the solid network filled with air. The network retains its original shape and size.

Preparation of aerogel can be summarized in simple four steps (see the sketch below):

Introduction

Because of their superior properties like extremely low density, outstanding sound and temperature insulation and high porosity, aerogels can be used in a vast diverse range of applications. For each of these unique properties, an innovative application is established, or there is an interest to explore its possible applications in that field. In this work biocompatible aerogels are used for pharmaceutical applications. Because of their high surface area (up to 1200 m2/g), open pore structure and non-toxicity, it is an ideal candidate for drug delivery systems.

Aim of the project

To design a drug carrier with tailorable loading and release properties for a specific applications in the area of drug targeting.

Aerogels from different precursors are used in this study: non-organic (functionilized silica) and organic precursors (starch, alginate, chitosan, agar, pectin or cellulose). The past activities were concentrated on silica aerogels, further step will be the use of biodegradable polymers as well as organic aerogels to design an advance drug carrier.

Methodology

Pharmaceutical substances have different chemical structures; as a result they have different affinity to the drug carriers, in this case aerogel. Thus, in order to load different pharmaceutical substances to the desired extent, different drug carriers should be produced and their properties should be tailored.

By means of surface functionalization, the properties of the aerogel can be tunable; different functional groups can be used to enhance the surface properties of aerogels to mach the needs of each drug substance. Controlling the surface coverage of the functional groups as well as their type is one of the goals of this study.

In general, functionalization can be divided into two basic classes:

1. Pre-treatment: in which the desired functional group participate in the sol-gel reactions to form a functionalised gel.
2. Post-treatment: in this method the surface properties of the produced aerogel can be changed by means of functionalization reactions.

Each class has its own methods and applications that allow us to open a wide window in the area of surface modifications of aerogels.

Drug loading and release studies

The loading of the targeted drug into the drug carrier (aerogel) is achieved in supercritical conditions, in which SCCO2 dissolve the drug and carry it to the surface of the aerogel where the adsorption take place, which gives the advantage of micronization of the drug substance to be later more easy released in the body.

The drug release measurements were carried out following the recommendations of the United States Pharmacopeia (USP XXI), a drug release apparatus was design and built according to these recommendations. The release experiment was done using a solution that simulates the targeted organ, a sample from the resulted solution was taken every 2-5 min to be investigated using UV-VIS spectroscopy.

Selected results

Innovative support materials for drug delivery: a view of an engineer. Wolfgang Arlt, Irina Smirnova. World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, Invited plenary lecture, Geneva 2006

Adsorption und Kristallisation von organischen Substanzen auf funktionalisierten Aerogelen. B.S.K. Gorle, S.Wille, R.Mallepally, I.Smirnova, W.Arlt. Plenarvortrag in Fachtugung AEM 2007 (Asselheim)

Relevant publications of our group

Smirnova I., Mamic J., Arlt W., „Adsorption of drugs on silica aerogels“ Langmuir, 19(20); 2003, 8521-8525

Smirnova, I.; Suttiruengwong, S.; Arlt, W; “Release of active substances from Aerogel active-substance formulations”. Chemie Ingenieur Technik (2003), 75(8), 1075-1076

Smirnova, I.; Arlt, W. “Synthesis of silica aerogels and their application as drug delivery system”. Supercritical Fluids as Solvents and Reaction Media (2004), 381-427; Editor(s): Brunner, G., Publisher: Elsevier B.V., Amsterdam

Smirnova I., Suttiruengwong S., Seiler M., Arlt. W. „Improvement of the solubility of poor soluble drugs by adsorption on silica aerogels “, Pharmaceutical Development and Technology, vol. 9 (4), 2004, 443-452

Smirnova, I.; Suttiruengwong, S.; Arlt, W; Feasibility study of hydrophilic and hydrophobic silica aerogels as drug delivery systems”. Journal of Non-Crystalline Solids (2004), 350, 54-60

Smirnova, I.; Tuerk, M.; Wischumerski, R.; Wahl, M. A. „Comparison of different methods for enhancing the dissolution rate of poorly soluble drugs: Case of griseofulvin”. Engineering in Life Sciences (2005), 5(3), 277-280 Smirnova, I.; Suttiruengwong, S.; Arlt, W. “Aerogels: tailor-made carriers for immediate and prolonged drug release”. KONA (2005), 23 86-