Clay and non-clay minerals in the pharmaceutical industry

Abstract

Minerals are widely used in the pharmaceutical industry as lubricants, desiccants, disintegrants, diluents, binders, pigments and opacifiers, as well as emulsifying, thickening, isotonic agents, and anticaking agents, and flavour correctors and carriers of active ingredients.

A variety of minerals are used as excipients in pharmaceutical preparations because they have certain desirable physical and physico-chemical properties, such as high adsorption capacity, specific surface area, swelling capacity, and reactivity to acids. Other important properties are water solubility and dispersivity, hygroscopicity, unctuosity, thixotropy, slightly alkaline reaction (pH), plasticity, opacity, and colour. Clearly such minerals must not be toxic to humans. The following minerals are commonly used as excipients: oxides (rutile, zincite, periclase, hematite, maghemite, magnetite), hydroxides (goethite), carbonates (calcite, magnesite), sulfates (gypsum, anhydrite), chlorides (halite, sylvite), phosphates (hydroxyapatite), and phyllosilicates (palygorskite, sepiolite, kaolinite, talc, montmorillonite, saponite and hectorite). More recently, some tectosilicates (zeolites) also feature in pharmaceutical preparations.

Minerals also enjoy the following medical/health applications: a) contrast diagnostic techniques, b) production of dental cements and dental molds in odontology, c) immobilization of limbs and fractures or dental and craniofacial surgical procedures in traumatology, d) bone grafts or construction of orbital implants, and e) spas and aesthetic centers. Examples of such minerals are oxides (zincite, magnetite and maghemite), sulphates (gypsum and barite), phosphates (hydroxyapatite) and phyllosilicates (clay minerals).

Introduction

Minerals are used in pharmaceutical preparations as either active ingredients (having therapeutic properties), or excipients. Whereas this paper deals with the use of minerals as excipients, a companion paper (next issue) reviews their use as active ingredients. Excipients are more or less inert minerals that determine the consistency, form, and volume of the pharmaceutical preparations. Some excipients have organoleptic properties (e.g., colour), induce liberation of the active ingredient within the organism, or facilitate the elaboration and conservation of the pharmaceutical preparation. Minerals also enjoy diagnostic, odontological, and traumatological applications, and are used in spas and aesthetic centers for therapeutic proposes (Fig. 1).

Although the market volume for pharmaceutical minerals is small, the added value is substantial, since the price of pharmaceutical grade minerals may be up to ten times that of the same minerals dedicated to other uses. This is because pharmaceutical minerals must meet the strict chemical, physical, and toxicological specifications set out in the European or United States Pharmacopoeia (López Galindo et al., 2007). Purification treatments, such as particle size fractionation, thermal treatment, and acid activation, improve the physical and physico-chemical properties of the minerals in question.

The majority of crystalline substances, used as either active ingredients or excipients, are synthetic analogues of the naturally occurring minerals (Carretero and Pozo; next issue). The few natural minerals that feature in pharmaceutical applications are there because they are abundant and inexpensive (e.g., calcite, halite, gypsum), or because their synthesis is complicated and costly (e.g., clay minerals).

The papers published until now related with minerals used in pharmaceutical industry show that besides being non-toxic to humans, some pharmaceutical minerals should have a high adsorption capacity, specific surface area, and swelling capacity as well as thixotropic and colloidal properties (Galan et al., 1985, Veniale, 1992, Bolger, 1995, Veniale, 1997, Carretero, 2002, Love, 2004, López Galindo and Viseras, 2004, Carretero et al., 2006, Droy-Lefaix and Tateo, 2006, Carretero and Pozo, 2007, Lefort et al., 2007, Viseras et al., 2007). No comprehensive review, however, is available on the all physical and physico-chemical properties of minerals that are used in the pharmaceutical industry.

The use of clay minerals and non-silicate minerals as excipients in pharmaceutical formulations has been described by many authors (Galan et al., 1985, Veniale, 1992, Bolger, 1995, Veniale, 1997, Carretero, 2002, Cerri et al., 2004, Love, 2004, López Galindo and Viseras, 2004, Carretero et al., 2006, Droy-Lefaix and Tateo, 2006, Carretero and Pozo, 2007, Del Hoyo, 2007, Lefort et al., 2007, Viseras et al., 2007, and references therein). Not all the minerals mentioned in the Pharmacopoeias, however, were included. Here we provide a comprehensive review on the use of minerals as excipients in pharmaceutical preparations, together with those used for diagnostic and other medical purposes. We have reviewed the papers published until now (and the references therein) so as the Pharmacopoeias. In each case, we attempt to correlate the physical and physico-chemical properties, and chemical composition of the minerals with their use in the pharmaceutical industry and/or health care centres.