Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Structural evolution of indomethacin particles upon milling: Time-resolved quantification and localization of disordered structure studied by IGC and DSC.

The amorphization of indomethacin was induced by milling. The mass fraction of the amorphous phase in the drug milled for various time intervals was determined with differential scanning calorimetry (DSC). Because the surface fraction amorphized by milling can be much higher than the mass fraction, which can have a large impact on the powder properties, a method for quantification of surface fraction amorphized by milling using inverse gas chromatography (IGC) was developed. A calibration curve was constructed by mixing completely amorphous indomethacin (obtained after milling for 120 min) with various amounts of the initial crystalline sample. Linear part of the curve was then used to quantify the surface amorphous content of samples milled for different time intervals. Surface and mass amorphization kinetics were determined and fitted to a first-order model. It was found that the surface amorphization rate is an order of magnitude higher than the mass amorphization rate. Results confirmed that IGC is a sensitive method for detection and quantification of the fraction of amorphous surface of milled indomethacin powder. If suitably combined with other techniques, this method represents a relatively general approach for the localization and quantification of the surface amorphous fraction in crystalline substances that transform into amorphous ones upon intensive milling

Vitrification from solution in restricted space: Formation and stabilization of amorphous nifedipine in a nanoporous silica xerogel carrier.

Purpose: The goal was to find thermodynamic criteria that must be satisfied in order to prevent formation of crystalline state of drugs within a confined space (e.g., nanopores of inorganic solid). Similarly, criteria that lead to stabilization of amorphous drug within such pores were investigated. Methods: In the theoretical part, the classical thermodynamics of nucleation is applied to the conditions of a restricted space. The theoretical findings are verified using porous silica as a carrier and nifedipine as a model drug. The amorphicity of the latter is checked using XRD and thermal analysis (DTA, DSC) in combination with BET measurements. Results: It is shown that there exists a critical pore radius of a host below which the entrapped substance will solidify in an amorphous form. There also exists a critical pore radius below which the entrapped amorphous solid will not be able to crystallize. Specifically, incorporation of NIF into a silica xerogel with an average pore diameter of about 2.5 nm produces and stabilizes its amorphous form. Conclusion: Entrapment of drugs into solid nanoporous carriers could be regarded as a potentially useful and simple method for production and/or stabilization of non-crystalline forms of a wide range of drugs

Novel hybrid silica xerogels for stabilization and controlled release of drug.

Purpose: The goal was to show that incorporation of a model drug into a porous solid matrix with small enough pores should lead to composites in which the drug would be in the amorphous rather than in the crystalline state. Due to spatial constraints, the amorphous state was expected to be temporally highly stable. Methods: As a porous solid matrix silica was selected, while nifedipine served as a model drug. The silica-drug composites were prepared using a sol-gel procedure at conditions which yielded pores in the range 2-3 nm. To tune the properties of composites, two silica precursors were combined: tetraethoxysiiane (TEOS) and bis-1,2-(triethoxysilyl)ethane (BTSE). Results: In all composites the amorphous state of nifedipine was proven using several analytical methods. The amorphicity was preserved for at least several months. Drug incorporation into purely TEOS-based silica decreased significantly the release rate. Loosening the structure by addition of BTSE, while preserving the amorphicity, increased the drug dissolution rate. The dissolution behaviour was explained using a combination of the Noyes-Whitney and power law model. Conclusion: The observed release patterns could be interesting for therapies requiring a high initial drug concentration in blood plasma, followed by a slower release rate of the remaining drug

The relation between the interfacial contact and SiO₂ coating efficiency and properties in the case of two clarithromycin polymorphs.

Two clarithromycin polymorphs with very similar particle size and morphology were coated with silica using a base-catalyzed sol-gel procedure. It was found that the contact angles, evaluated from measured surface free energies, correlate well with coating efficiency. The connection between interfacial contact (described with the contact angle), nucleation kinetics and coating performance was established using the heterogeneous nucleation theory. The resulting coating thickness and morphology were evaluated by means of thermal analysis. X-ray powder diffraction and scanning electron microscopy. Good agreement was found between the theoretical predictions and experimental findings