Data-driven modeling of the bicalutamide dissolution from powder systems

Low solubility of active pharmaceutical compounds (APIs) remains an important challenge in dosage form development process. In the manuscript, empirical models were developed and analyzed in order to predict dissolution of bicalutamide (BCL) from solid dispersion with various carriers. BCL was chosen as an example of a poor watersoluble API. Two separate datasets were created: one from literature data and another based on in-house experimental data. Computational experiments were conducted using artificial intelligence tools based on machine learning (AI/ML) with a plethora of techniques including artificial neural networks, decision trees, rule-based systems, and evolutionary computations. The latter resulting in classical mathematical equations provided models characterized by the lowest prediction error. In-house data turned out to be more homogeneous, as well as formulations were more extensively characterized than literature-based data. Thus, in-house data resulted in better models than literature-based data set. Among the other covariates, the best model uses for prediction of BCL dissolution profile the transmittance from IR spectrum at 1260 cm−1 wavenumber. Ab initio modeling–based in silico simulations were conducted to reveal potential BCL–excipients interaction. All crucial variables were selected automatically by AI/ML tools and resulted in reasonably simple and yet predictive models suitable for application in Quality by Design (QbD) approaches. Presented data-driven model development using AI/ML could be useful in various problems in the field of pharmaceutical technology, resulting in both predictive and investigational tools revealing new knowledge

Development and verification of new solid dental filling temporary materials containing zinc : formula development stage

Caries is the most popular problem affecting teeth and this is the reason why so many temporary dental filling materials are being developed. An example of such filling is zinc oxide paste mixed with eugenol, Thymodentin and Coltosol FÆ. Zinc-oxide eugenol is used in dentistry because of its multiplied values: it improves heeling of the pulp by dentine bridge formation; has antiseptic properties; is hygroscopic. Because of these advantages compouds of zinc oxide are used as temporary fillings, especially in deep caries lesions when treatment is oriented on support of vital pulp. Temporary dental fillings based on zinc oxide are prepared ex tempore by simple mixing powder (Thymodentin) and eugenol liqiud together or a ready to use paste Coltosol FÆ. Quantitative composition depends mainly on experience of person who is preparing it, therefore, exact qualitative composition of dental fillings is not replicable. The main goal of the study was to develop appropriate dental fillings in solid form containing set amount of zinc oxide. Within the study, the influence of preparation method on solid dental fillings properties like mechanical properties and zinc ions release were examined

Molecular disorder of bicalutamide : amorphous solid dispersions obtained by solvent methods

The effect of solvent removal techniques on phase transition, physical stability and dissolution of bicalutamide from solid dispersions containing polyvinylpyrrolidone (PVP) as a carrier was investigated. A spray dryer and a rotavapor were applied to obtain binary systems containing either 50% or 66% of the drug. Applied techniques led to the formation of amorphous solid dispersions as confirmed by X-ray powder diffractometry and differential scanning calorimetry. Moreover, solid–solid transition from polymorphic form I to form II was observed for bicalutamide spray dried without a carrier. The presence of intermolecular interactions between the drug and polymer molecules, which provides the stabilization of molecularly disordered bicalutamide, was analyzed using infrared spectroscopy. Spectral changes within the region characteristic for amide vibrations suggested that the amide form of crystalline bicalutamide was replaced by a less stable imidic one, characteristic of an amorphous drug. Applied processes also resulted in changes of particle geometry and size as confirmed by scanning electron microscopy and laser diffraction measurements, however they did not affect the dissolution significantly as confirmed by intrinsic dissolution study. The enhancement of apparent solubility and dissolution were assigned mostly to the loss of molecular arrangement by drug molecules. Performed statistical analysis indicated that the presence of PVP reduces the mean dissolution time and improve the dissolution efficiency. Although the dissolution was equally affected by both applied methods of solid dispersion manufacturing, spray drying provides better control of particle size and morphology as well as a lower tendency for recrystallization of amorphous solid dispersions

How does the CO2 in supercritical state affect the properties of drug-polymer systems, dissolution performance and characteristics of tablets containing bicalutamide?

The increasing demand for novel drug formulations has caused the introduction of the supercritical fluid technology, CO2 in particular, into pharmaceutical technology as a method enabling the reduction of particle size and the formation of inclusion complexes and solid dispersions. In this paper, we describe the application of scCO2 in the preparation of binary systems containing poorly soluble antiandrogenic drug bicalutamide and polymeric excipients, either Macrogol 6000 or Poloxamer®407. The changes in the particle size and morphology were followed using scanning electron microscopy and laser di raction measurements. Di erential scanning calorimetry was applied to assess thermal properties, while X-ray powder di ractometry was used to determine the changes in the crystal structure of the systems. The dissolution of bicalutamide was also considered. Binary solid dispersions were further compressed, and the attributes of tablets were assessed. Tablets were analyzed directly after manufacturing and storage in climate chambers. The obtained results indicate that the use of supercritical CO2 led to the morphological changes of particles and the improvement of drug dissolution. The flowability of blends containing processed binary systems was poor; however, they were successfully compressed into tablets exhibiting enhanced drug release

Compression-Induced Phase Transitions of Bicalutamide

The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively.Polish National Science Centre 2015/16/W/NZ7/0040

Molecular dynamics and physical stability of ibuprofen in binary mixtures with an acetylated derivative of maltose

In this paper, we explore the strategy increasingly used toimprove the bioavailability of poorly water-soluble crystalline drugs byformulating their amorphous solid dispersions. We focus on the potentialapplication of a low molecular weight excipient octaacetyl-maltose (acMAL) toprepare physically stable amorphous solid dispersions with ibuprofen (IBU)aimed at enhancing water solubility of the drug compared to that of itscrystalline counterpart. We thoroughly investigate global and local moleculardynamics, thermal properties, and physical stability of the IBU+acMAL binarysystems by using broadband dielectric spectroscopy and differential scanningcalorimetry as well as test their water solubility and dissolution rate. Theobtained results are extensively discussed by analyzing several factorsconsidered to affect the physical stability of amorphous systems, includingthose related to the global mobility, such as plasticization/antiplasticization effects, the activation energy, fragility parameter, and thenumber of dynamically correlated molecules as well as specific intermolecular interactions like hydrogen bonds, supporting the latterby density functional theory calculations. The observations made for the IBU+acMAL binary systems and drawn recommendationsgive a better insight into our understanding of molecular mechanisms governing the physical stability of amorphous solid dispersions

Fragrant starch-based films with limonene

Novel fragrant starch-based films with limonene were successfully prepared. Biodegradable materials of natural origin were used and the process was relatively simple and inexpensive. The effect of limonene on physicochemical properties of starch-based films (moisture absorption, solubility in water, wettability, mechanical properties) were compared to glycerol plasticized system. Taking into consideration that the obtained materials could also exhibit bactericidal and fungicidal properties, the studies with Escherichia coli, Candida albicans and Aspergillus niger were performed. Such a material could potentially find application in food packaging (e.g. masking unpleasant odors, hydrophilic starch film would prevent food drying), or in agriculture (e.g. for seed encapsulated tapes)

The role of MRI in diagnostic algorithm of cervicofacial vascular anomalies in children

Background: Vascular anomalies are usually diagnosed through their clinical picture and history. The purpose of this study was to assess the role of MR imaging in initial assessment of cervicofacial vascular anomalies in children. Material/Methods: Twenty pediatric patients with vascular anomalies located in the cervicofacial region underwent MRI examination in our department. Images were evaluated for lesion detectability and its signal characteristics (on T1w, T2w images with fat suppression and contrast enhanced T1w sequences); the extent of the lesions and surrounding tissue involvement were also assessed. Results: In the studied group MR images revealed all anomalies and provided information of their anatomic extent and invasion of surrounding anatomic structures. Nine hemangiomas and six venous malformations were found among studied patients. Two children had multiloculated lesions corresponding to lymphatic malformations. One examination visualized a lesion consisting mainly of dilated vascular channels with an apparent feeding artery, which was consistent with arteriovenous malformation. Two remaining lesions were mixed malformations. Nine patients had lesions limited to subcutaneous tissue. Two masses infiltrated bone structures. There was muscle involvement found in nine cases. Conclusions: MR imaging is a well-established method for detection and monitoring of vascular anomalies in children. With ultrasound used mostly for initial diagnosis and additional flow assessment, angiography viewed as an invasive therapeutic method and computed tomography used only in specific situations due to its high irradiation dose, magnetic resonance is the best imaging method used in differential diagnosis and topographical characterization of vascular malformations and tumors of cervicofacial area in pediatric patients. Noninvasively and without irradiation, it enables evaluation of the extent and characteristics of lesions and planning proper therapeutic strategy