Surface area normalized dissolution to study differences in itraconazole-copovidone solid dispersions prepared by spray-drying and hot melt extrusion.

Amorphous solid dispersions of itraconazole (ITZ) and copovidone (PVPVA 64) at 1:1 to 1:9 drug-polymer ratios were prepared using spray-drying (SD) and hot melt (HM) extrusion for comparative evaluation. Surface area normalized dissolution studies were carried out using a modified intrinsic dissolution rate (IDR) assembly and rate of release of drug as well as polymer were quantified using ultraviolet spectroscopy. The melt quenched amorphous form of ITZ provided an 18-fold dissolution advantage over the crystalline form. In general, dispersions prepared by either SD or HM showed similar dissolution profiles in terms of drug release. Both drug-controlled and polymer-controlled ITZ dissolution rates were observed, depending on the drug loading, where a switch from a drug-controlled to a polymer-controlled regime was observed when the drug loading was approximately 20% or lower. The impact of the spray drying solvent composition was studied and found to have a large effect on the drug release rate for dispersions containing a drug loading of 20%. Electron microscopy showed differences in surface morphology (scanning) and internal structure (transmission) in these dispersions as a function of solvent system. X-ray photoelectron spectroscopy (XPS) revealed differences in the surface composition of drug and polymer whereby poorly dissolving systems showed drug enrichment. This study provides insight into the complex interplay between formulation, processing and performance of amorphous solid dispersion systems.

Amorphization of thiamine chloride hydrochloride: A study of the crystallization inhibitor properties of different polymers in thiamine chloride hydrochloride amorphous solid dispersions.

Amorphous solid dispersions of thiamine chloride hydrochloride (THCl) were created using a variety of polymers with different physicochemical properties in order to investigate how effective the various polymers were as THCl crystallization inhibitors. THCl:polymer dispersions were prepared by lyophilizing solutions of THCl and amorphous polymers (guar gum, pectin, κ-carrageenan, gelatin, and polyvinylpyrrolidone (PVP)). These dispersions were stored at select temperature (25 and 40°C) and relative humidity (0, 23, 32, 54, 75, and 85% RH) conditions and monitored at different time points using powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Moisture sorption isotherms of all samples were also obtained. Initially amorphous THCl was produced in the presence of ≥40% w/w pectin, κ-carrageenan, gelatin, and guar gum or ≥60% w/w PVP. Trends in polymer THCl crystallization inhibition (pectin≥κ-carrageenan>gelatin>guar gum≫PVP) were primarily based on the ability of the polymer to interact with THCl via hydrogen bonding and/or ionic interactions. The onset of THCl crystallization from the amorphous dispersions was also related to storage conditions. THCl remained amorphous at low RH conditions (0 and 23% RH) in all 1:1 dispersions except THCl:PVP. THCl crystallized in some dispersions below the glass transition temperature (Tg) but remained amorphous in others at T~Tg. At high RHs (75 and 85% RH), THCl crystallized within one day in all samples. Given the ease of THCl amorphization in the presence of a variety of polymers, even at higher vitamin concentrations than would be found in foods, it is likely that THCl is amorphous in many low moisture foods.

Effect of amorphous content on dissolution characteristics of rifampicin.

Rifampicin, one of the main first line anti-TB drugs, shows variable bioavailability in different marketed preparations and reasons cited include physiological, degradation, manufacturing/ processing, solid state, and bioavailability assessment procedure. Although the amorphous form of a drug is expected to exhibit higher solubility, the amorphous rifampicin has been reported to have a solubility disadvantage as compared to crystalline form II, which is used in marketed preparations. Amorphous form was generated and characterized by solid-state characterization techniques. Physical powder mixtures of form II with varying amounts of amorphous form were prepared, which were then subjected to solid-state characterization techniques and further evaluated for their dissolution behavior. Differential scanning calorimetry (DSC) scans show that area enclosed by integral of melting endotherm can be used for quantification of crystalline component, which can then be used to estimate amorphous content. No definite trend was evident in powder dissolution of mixtures that could implicate solubility difference of amorphous form. Intrinsic dissolution rate (IDR) results indicate that amorphous content has no effect on dissolution profiles of crystalline rifampicin.

Disease, destination, dose and delivery aspects of ciclosporin: the state of the art.

Since its discovery in 1971, ciclosporin has revolutionized organ transplantation and the treatment of autoimmune disorders. The wide array of applications resulting from its clinical efficacy warrant unique administration strategies and varying doses, times of exposure and extents of distribution, depending on target tissue. The poor biopharmaceutical characteristics of low solubility and permeability makes this uphill task even more challenging for the drug delivery scientist. Efforts underway have explored various body routes employing approaches like emulsions, microspheres, nanoparticles, liposomes, iontophoresis and penetration enhancers. This review attempts a brief holistic view of the "four Ds" (disease, destination, dose and delivery) surrounding this immunomodulator drug.