System Design

OMS evaluation and usage has to date been largely limited to laboratory studies. Commercial medications incorporating such technology have not yet been developed. Whenever in vivo (animal) studies were conducted, the drug-loaded silica powder was filled into hard gelatin capsules and administered as such, without further downstream processes. Thus, the design of OMS-based formulations is, as yet, very basic. However, a variety of OMS materials have been used for drug delivery applications and each of these materials exhibit specific features that can affect capability to formulate or pharmaceutical performance. This section gives a brief overview of how OMS materials are manufactured, and how differences in material characteristics might affect applicability.

OMS is manufactured by a sol-gel-derived process. Surfactants or polymers are included as a template for the polymerizing silica. After polymerization, the

Addition of a silica source

Template

Template

Supramolecular assembly

Addition of a silica source

Supramolecular assembly

Fig. 10.3 Schematic for the synthesis of OMS

template is removed by chemical or thermal treatment, creating pores. The general pathway is depicted schematically in Fig. 10.3.

Template-assisted synthesis provides a material possessing an array of uniform pores that can be designed to diameters ranging from 2 nm to several tens of nanometers. The term "ordered" denotes that such materials exhibit long-range ordering (reflected in their X-ray diffraction patterns) [31, 32], although the pore walls comprise amorphous silica. Frequently used OMS materials for drug delivery are MCM-41 and SBA-15.

MCM-41 (after Mobil Composition of Matter) was first prepared in 1992 [33]. A quaternary ammonium surfactant is used as the structure-directing agent. MCM-41 possesses a regular array of uniform channels whose dimensions can be tailored (in the range 1.6-10 nm) through the choice of surfactant, auxiliary chemicals, and reaction conditions. The length of the alkyl chain of the surfactant determines pore diameter. Due to its relatively small pore diameter, MCM-41 has frequently been used in studies where slow drug release was envisaged.

SBA-15 (after Santa Barbara Amorphous) was first prepared in 1998. It employs amphiphilic poly(alkylene oxide) triblock copolymers as templates [34]. Appropriate polymer selection and processing conditions can provide pore diameters in the range of 5-30 nm. A transmission electron microscopy picture of an SBA-15 particle is depicted in Fig. 10.4. Its larger pore size makes SBA-15 the material of choice for fast drug release. In addition to uniform mesopores, SBA-15 possesses a complementary system of disordered micropores (diameter <2 nm) that protrude from the mesopore wall. Depending on the synthesis conditions, these micropores may or may not form interconnections between neighboring mesopores. The pore walls of SBA-15 are thicker (3-6 nm) than those of MCM-41 (1 nm), which is reflected in the higher hydrothermal stability of the former [34]. The relatively wide pore diameter of SBA-15, together with its high internal pore volume enable high drug loadings, reportedly up to 40% [35, 36].

Fig. 10.4 Transmission electron microscopy picture of an SBA-15 particle, illustrating the array of uniform pores (left hand side of the picture) and the honeycomb type structure (right hand side)

Fig. 10.4 Transmission electron microscopy picture of an SBA-15 particle, illustrating the array of uniform pores (left hand side of the picture) and the honeycomb type structure (right hand side)

Table 10.1

Mesoporous silica materials for drug delivery

Pore

Surface

Pore

Literature

diametera (nm)

areaa (m2/g)

volume a (cm3/g)

Structure

exampleb

SBA-15

5-25

700-1,000

0.5-1.25

Hexagonally ordered, 1D

[9]

MCM-41

2-10

1,000-1,500

0.7-1.2

Hexagonally ordered, 1D

[5]

MCM-48

2-6

1,000-1,500

0.7-1.2

Cubic, 3D

[37]

TUD-1

2.5-25

500-1,000

0.6-1.7

Foam-like, 3D

[38]

FSM-16

1.5-3.2

700-1,000

0.3-0.8

Hexagonally ordered, 1D

[39]

a The range indicates the values that are typically encountered for drug delivery applications. Modification of template and synthesis parameters may result in more extreme values than those reported in this table b Reference to an article where the material has been used in the context of drug delivery

Other mesoporous silica-based materials that have been used for drug delivery include:

• TUD-1 exhibiting a foam-like mesopore network.

• FSM-16 a highly ordered mesoporous silicate prepared via surfactant intercalation in a layered silica source.

• MCM-48 exhibiting a pore network comprising two independent and intricately interwoven systems of mesoporous channels.

The properties of these and other mesoporous materials are summarized in Table 10.1.

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