Nano-thermal analysis is a primary technique used in the study of the characteristics of pharmaceutical materials in the initial phase of drug design and development. Some of the drug properties that can be studied using nano-thermal analysis include the spatial distribution of the constituents, shape, and size particularly in multicomponent drug sample. Using nano-thermal procedures the different components of these multicomponent drugs can be studied and characterized without having to dissociate the drug. The technique is particularly useful in increasing the dissolution of drugs with low water solubility hence improve their bioavailability. This is by facilitating the formation of solid solution of drugs in soluble water polymer. This is important because the dissolution rate of drugs in aqueous medium plays a major role in the drug efficacy, toxicology and stability. The technique enhances stabilization of solid solution of the drug by preventing the crystallization of small domains of the drug which has an impact on the drug efficacy and stability.
Nano-thermal analysis methods have higher resolution imaging potential enhanced by combining thermal analysis methods with high resolution imaging capabilities of atomic force microscopy to form a localized analysis technique . Therefore nano-thermal technique has capabilities of imaging and quantitatively characterizing the nanoscale properties of solid dispersion formulation. Micro/Nano-thermal analysis is often combined with other techniques by replacing the thermal probe with the specific instrument such as X-ray photoelectron spectroscopy, atomic force microscopy and inverse gas chromatography to overcome the shortcomings of conventional thermal techniques e.g modulated temperatures DSC and differential scanning calorimetry which are bulk measurement techniques (lack sensitivity limits) and give a sum of the specimen constituents. This increases the types of analysis that can be performed. Therefore nano-thermal analysis has a wide range of applications in drug research and development.
2.0 uses of nano-thermal techniques in analysis of pharmaceutical compounds
The use of nano-thermal techniques in the pharmaceutical industry is diverse. The nino-thermal probe is used in mapping drugs in three dimensions by imaging the drug morphology thus the characteristics and the formation of the drug can be studied. The nano-thermal probes make it possible for an analyst to compare physico-chemical characteristics with the special mapping of drug surfaces, especially the drug coatings. The sample properties can be outlined through the development of a three-dimensional image and these characteristics may include pulsed-force-mode (PFM) and atomic force microscopy (AFM).
The analysis makes it possible to illustrate the different drug characteristics when subjected to different temperature changes. One of the major advantages of nano-thermal technique is that it is highly localized thus the risk of permanently changing drug sample is avoided (the drug is analyzed in situ in original unheated state). This pharmaceutical application enables easy differentiation of constituents of multicomponent drugs in their physical state by analyzing specific regions of the drug. Solid state is the most common in pharmaceutical products. The technique is particularly useful with the high drug loaded formulation in the identification of the solid state transition with the lower loaders. Nano-thermal techniques are used in different specific pharmaceutical analysis as outlined below.
3.0 Analysis of the structure of the solid dosage forms.
Some of the most crucial factors in the process of drug design are the structure of the active compound as well as the associated compounds (expients). These aspects play a crucial role in determining the performance of the drugs in terms of solubility, wettability and hardness as well as the handling properties. Through nao-thermal imaging the surface structure of both the active pharmaceutical ingredients (API) and the expient (carrie molecules) can be identified as uneven (corrugated) or smooth which can influence the aerosolization efficiency, inter-particle contact area and forces as well as the lung disposition of dry powder inhalers (Hancock & Parks, 2000). The surface characteristics of the API and the expients that are analyzed using nano-thermal analysis include the inter-particle interactions, the surface structure and the contact area. These characteristics ought to be optimized to facilitate optimum interactions between the API and the expient such that the bond between the two is strong enough for drug stability and yet weak enough to allow easy dissociation of the drug upon reaching the target organ. The nano-thermal technique offer unique insight into these drug characteristics hence enables the optimization and the modification. In addition this technique allows the anticipation of drug behavior at the initial phase of drug development.
4.0 Identification of various solid forms
4.1 Identification of Amorphous drugs
Amorphous drugs, unlike crystalline ones, are not in thermodynamically stable phase (they are metastable) and show no long-range molecular packing order in three dimension of space (orientation and position) thus lack molecular order in long range . Physicochemical properties of the metastable phase (amorphous state) include higher bioavailability, disordered with higher entropy i.e. higher molecular weight, higher physical and chemical degradation kinetics, less stability over pharmaceutical relevant time scales and higher solubility. In gaining higher solubility of amorphous form in the recent years pharmaceutical development is being conducted due to the high molecular mobility and the link of lower physical and chemical stability.
4.2 Identification of Polymorphic drugs
Crystalline polymorphs within tablet samples as well as the tablet coating can be analyzed with the localized thermal analysis in situ. The most marketed pharmaceutical product is in solid state. In this form the structural unit contains both the long-range and the short-range molecular order i.e. the crystalline materials have units repeated in a regular and a well defined lattice form. These forms include polymorphs and pseudopolymorphs. The crystalline materials have distinctive lattice structures i.e. molecular conformation without alteration in its chemical composition for the polymorphs. Pseudopolymorphs are described as crystalline hydrates for those with water bound molecules and solvates for those with organic bound solvent molecules in their crystalline state. On different solid phase of an API, properties such as melting point, stability, density, color, solubility and morphology may differ. This in turn influences the physical and chemical stability, process ability and bioavailability
Thermal microscopy and localized thermal analysis have shown to distinguish between components within drug-loaded, solid dispersions, pharmaceutical tablets and polymeric microsperes. Storage is minimized for the thermodynamically stable crystalline form since the risk of state transformation during the processing stages. Higher Gibbs free energy is exhibited over time with the thermodynamically form the less stable solid form eventually converts to a more stable form with lower Gibbs free energy. In pharmaceutical science material the solid state is crucial. In the solid state a bright occluded phase indicating presence of CBZ nanocrystal and a continous matrix associated to HPMZ ranging to 50mm in size. This morphology is noted to contain carbamazepine (CBZ) and hydroxyprophyl methyl cellulose (HPMC) in a polymer ration of 50/50 in the pharmaceutical system.
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