Andriy Dashevskiy

Solid self-emulsifying phospholipid suspension (SSEPS) with diatom as a drug carrier.

We report the application of diatom as a solid carrier for water insoluble drugs applied in oral drug delivery system based on the self-emulsifying drug delivery system (SEDDS) caprylocaproyl macrogol-8 glycerides/lecithin/propylene glycol/caprylic/capric triglyceride. Diatoms are fossilized skeletons of photosynthetic algae with complex 3-dimensional (3D), porous structure consisting of amorphous silica, obtained by purification of diatomaceous earth. Different solid samples of carbamazepine (CBZ) suspension in SEDDS, called solid self-emulsifying phospholipid suspension (SSEPS), were prepared using two methods: adsorption of CBZ dispersion in SEDDS by gentle mixing with diatoms in mortar with pestle (Method A) or dispersion of diatoms in ethanol solution of CBZ and SEDDS components, followed by ethanol evaporation (Method B). Release rate of CBZ from SSEPS was significantly higher in comparison to pure drug, physical mixture of diatoms and CBZ as well as solid dispersion of pure CBZ and diatoms obtained by ethanol evaporation. The dissolution of CBZ from SSEPS sample prepared using method B was faster than from the sample prepared by the method A. Higher dissolution for sample prepared by the method B can be attributed to the partial adsorption (deeper localization) of liquid material inside the pores of diatoms. Upon storage of the samples under accelerated conditions (40°C and 70% RH) for 10 weeks no significant changes in CBZ crystallinity and dissolution was in case of SSEPS, contrary to solid dispersion with increased crystallinity, indicating that diatoms with adsorbed liquid CBZ-loaded SEPS can maintain initial CBZ characteristics.

Curing mechanism of flexible aqueous polymeric coatings

&NA; The objective of this study was to explain curing phenomena for pellets coated with a flexible polymeric coating based on poly(vinyl acetate) (Kollicoat® SR 30D) with regard to the effect of starter cores, thickness of drug layer, adhesion of coating to drug‐layered‐cores as well as coating properties. In addition, appropriate approaches to eliminate the curing effect were identified. Sugar or MCC cores were layered with the model drugs carbamazepine, theophylline, propranolol HCl, tramadol HCl and metoprolol HCl using HPMC (5 or 25% w/w, based on drug) as a binder. Drug‐layered pellets were coated with Kollicoat® SR 30D in a fluidized bed coater using TEC (10% w/w) as plasticizer and talc (35–100% w/w) as anti‐tacking agent. Drug release, pellet properties (morphology, water uptake‐weight loss and osmolality) and adhesion of the coating to the drug layer were investigated as a function of curing at 60 °C or 60 °C/75% RH for 24 h. The film formation of the aqueous dispersion of Kollicoat® SR 30D was complete, and therefore, a strong curing effect (decrease in drug release) at elevated temperature and humidity (60 °C/75% RH) could not be explained by the well‐known hydroplasticization and the further gradual coalescence of the colloidal polymer particles. According to the provided mechanistic explanation, the observed curing effect was associated with (1) high flexibility of coating, (2) adhesion between coating and drug layer, (3) water retaining properties of the drug layer, and (4) osmotically active cores. Unwanted curing effects could be minimized/eliminated by the addition of talc or/and pore‐forming water soluble polymers in the coating, increasing binder amount or applying an intermediate coating, by increasing the thickness of drug layer or using non‐osmotic cores. A new insight into curing phenomena mainly associated with the adhesion between drug layer and coating was provided. Appropriate approaches to avoid unwanted curing effect were identified. Graphical abstract Figure. No caption available.

Development of a discriminative biphasic in vitro dissolution test and correlation with in vivo pharmacokinetic studies for differently formulated racecadotril granules

&NA; The purpose of this study was to discriminate the release behavior from three differently formulated racecadotril (BCS II) granules and to establish an in vitro‐in vivo correlation. Three granule formulations of the lipophilic drug were prepared with equivalent composition but prepared with different manufacturing processes (dry granulation, wet granulation with or without binder). In vitro release of the three granules was investigated using a biphasic dissolution system (phosphate buffer pH 6.8 and octanol) and compared to the conventional single phase USP II dissolution test performed under sink and non‐sink conditions. In vivo studies with each granule formulation were performed in rats. Interestingly, the granule formulations exhibited pronouncedly different behavior in the different dissolution systems depending on different wetting and dissolution conditions. Single phase USP II dissolution tests lacked discrimination. In contrast, remarkable discrimination between the granule formulations was observed in the octanol phase of biphasic dissolution system with a rank order of release from granules prepared by wet granulation with binder > wet granulation without binder > dry granulation. This release order correlated well with the wettability of these granules. An excellent correlation was also established between in vitro release in the octanol phase of the biphasic test and in vivo data (R2 = 0.999). Compared to conventional dissolution methods, the biphasic method provides great potential to discriminate between only minor formulation and process changes within the same dosage form for poorly soluble drugs. Graphical abstract Figure. No caption available.

Micropellets coated with Kollicoat® Smartseal 30D for taste masking in liquid oral dosage forms

Abstract The objective of this study was to develop delivery systems for taste masking based on multiparticulates coated with Kollicoat® Smartseal 30D formulated as liquid oral suspensions. Coating of particles containing bitter drugs with Kollicoat® Smartseal reduced drug leaching into aqueous medium, especially when increasing pH, therefore can be used for the formulation of liquid dosage forms. Application of an intermediate layer of ion exchange resins between drug layer and coating can further decrease drug leaching into aqueous vehicle that is beneficial in terms of taste masking. Using optimized compositions of liquid vehicles such as addition of sugar alcohols and ion exchange resin, reconstitutable or ready-to-use liquid dosage forms with micropellets can be developed with bitter taste protection after redispersion lasting longer than 3 weeks, which exceeds the usual period of application.