Mesoporous Drug Delivery System: From Physical Properties of Drug in Solid State to Controlled Release

Abstract

Mesoporous materials, which exhibit great potential in the control of polymorphs and delivery of poorly water-soluble drugs, have obtained considerable attention in the field of pharmaceutical science. The physical properties and release behaviors of amorphous or crystalline drugs may be affected by formulating them into mesoporous drug delivery systems. In the past few decades, an increasing amount of papers have been written about mesoporous drug delivery systems, which play a crucial role in improving the properties of drugs. Herein, mesoporous drug delivery systems are comprehensively reviewed in terms of their physicochemical characteristics, control of polymorphic forms, physical stability, in vitro performance, and in vivo performance. Moreover, the challenges and strategies of developing robust mesoporous drug delivery systems are also discussed.

Keywords: confined crystallization; controlled release; in vitro and in vivo performance; mesoporous drug delivery system; polymorph control.

Figure 1

Percent of the change in heat capacity (Φ_ads) for the T_g of the interfacial layer, as a function of cooling rate for griseofulvin confined in AAO templates with different pore diameters. Φ_ads is deduced from the change in heat capacity in the T_g,high region, can be calculated as △C_p,high/(△C_p,high + △C_p,inter + △C_p,low). For these cooling rate-dependency experiment, these confine samples are firstly heated above melting point and followed by a cooling process with different rates. T_g and ΔCp values are obtained from the subsequent heating curves with a 10 K/min rate. Adapted from the Ref. [10] with the permission. (Copyright © 2023 American Chemical Society).

Figure 2

(a) ¹H-¹³C CPMAS NMR results of vortioxetine crystals and vortioxetine-mesoporous silica materials composites; (b) chemical shift of the ortho-carbon atom of vortioxetine of vortioxetine in composites. Herein, solid stars represent the NMR signal of the ortho-carbon atom. Adapted from the Ref. [26] with the permission. (Copyright © 2023 American Chemical Society).

Figure 3

(a) The dielectric spectra of celecoxib with different concentrations of Syloid 244FP are recorded at a given temperature. Dashed line represents the shape analysis of the structural relaxation peak in terms of Kohlrausch–Williams–Watts (KWW) function. (b) Value of β_KWW as a function of Syloid 244FP concentration. Adapted from the Ref. [20] with the permission. (Copyright © 2023 Elsevier).

Figure 4

Gibbs–Thomson equation fitting for A and B melting peaks. A and B melting peaks are observed in the melting region for bulk nifedipine and confined nifedipine as a function of pore size. A melting peak is recognized as form A of nifedipine while B melting peak is marked as unknown polymorph transition peak. Adapted from the Ref. [27] with the permission. (Copyright © 2023 American Chemical Society).

Figure 5

(a) Donor, total drug release and (b) receiver concentration of ketoconazole mesoporous silica-based formulations during dissolution-absorption measurements with pH shifting from pH 1 to 6.8 after 30 min. Donor concentration exhibits an abrupt decline and is followed by a further gradual decline. Receiver concentration exhibits a maximum and a gradual decline in concentration follows. Only slight increase of total drug release (by 10%) can be observed over 4 h. Adapted from the Ref. [46] with the permission. (Copyright © 2023 American Chemical Society).

Figure 6

Ritonavir concentration versus time profiles in the receiver compartment in vitro diffusion studies for the ritonavir-loaded SBA-15 systems by using a side-by-side diffusion cell with different drug doses (% of its amorphous solubility). A known quantity of sample is first added into the donor compartment to obtain the desired total drug concentration. Then, drug concentration in receiver compartment is monitored as a function of time through periodically withdrawing 100 µL aliquots and diluting with 50 µL acetonitrile. Adapted from the Ref. [48] with the permission. (Copyright © 2023 American Chemical Society).

Figure 7

Dissolution behaviors of itraconazole binary and ternary ASD tablets by using USP apparatus II under non-sink conditions. Before testing, 500 mL of pH 6.8 phosphate buffer is added to the dissolution vessel and maintained at 37 °C. Paddle speed is set to 100 rpm. Samples containing 100 mg itraconazole first pass through 212 μm sieves and are immediately added into the vessel. Aliquots are collected at time points of 15 min, 30 min, 1 h, 2 h, 4 h, and 6 h. Adapted from the Ref. [54] with the permission. (Copyright © 2023 American Chemical Society).

Figure 8

Overview of superior properties and possible future research directions of the mesoporous materials in the pharmaceutical field.