Dr. Zahari Vinarov
Drug Delivery and Disposition unit, KU Leuven, Leuven, Belgium
+1
'%3e%3cpath%20d='M22.1642%2019.0924C21.7317%2018.068%2021.1041%2017.1375%2020.3163%2016.3527C19.5309%2015.5656%2018.6006%2014.9381%2017.5766%2014.5048C17.5674%2014.5002%2017.5582%2014.4979%2017.5491%2014.4933C18.9774%2013.4616%2019.9059%2011.7811%2019.9059%209.88504C19.9059%206.74408%2017.3611%204.19922%2014.2201%204.19922C11.0792%204.19922%208.53429%206.74408%208.53429%209.88504C8.53429%2011.7811%209.46282%2013.4616%2010.8912%2014.4956C10.882%2014.5002%2010.8728%2014.5025%2010.8636%2014.5071C9.83652%2014.9404%208.91487%2015.5617%208.1239%2016.355C7.33685%2017.1404%206.70933%2018.0707%206.276%2019.0947C5.85031%2020.0972%205.62072%2021.172%205.59967%2022.2609C5.59905%2022.2853%205.60335%2022.3097%205.61229%2022.3325C5.62123%2022.3553%205.63465%2022.376%205.65174%2022.3935C5.66883%2022.4111%205.68926%2022.425%205.71182%2022.4345C5.73437%2022.444%205.7586%2022.4489%205.78308%2022.4489H7.15868C7.25956%2022.4489%207.3398%2022.3686%207.3421%2022.2701C7.38795%2020.5001%208.09868%2018.8425%209.35506%2017.5861C10.655%2016.2862%2012.3814%2015.5709%2014.2201%2015.5709C16.0588%2015.5709%2017.7852%2016.2862%2019.0852%2017.5861C20.3415%2018.8425%2021.0523%2020.5001%2021.0981%2022.2701C21.1004%2022.3709%2021.1807%2022.4489%2021.2815%2022.4489H22.6571C22.6816%2022.4489%2022.7058%2022.444%2022.7284%2022.4345C22.751%2022.425%2022.7714%2022.4111%2022.7885%2022.3935C22.8056%2022.376%2022.819%2022.3553%2022.8279%2022.3325C22.8369%2022.3097%2022.8412%2022.2853%2022.8406%2022.2609C22.8176%2021.165%2022.5907%2020.0989%2022.1642%2019.0924ZM14.2201%2013.8284C13.1678%2013.8284%2012.1773%2013.418%2011.4322%2012.6729C10.6871%2011.9278%2010.2767%2010.9374%2010.2767%209.88504C10.2767%208.83271%2010.6871%207.84227%2011.4322%207.09715C12.1773%206.35204%2013.1678%205.94165%2014.2201%205.94165C15.2724%205.94165%2016.2629%206.35204%2017.008%207.09715C17.7531%207.84227%2018.1635%208.83271%2018.1635%209.88504C18.1635%2010.9374%2017.7531%2011.9278%2017.008%2012.6729C16.2629%2013.418%2015.2724%2013.8284%2014.2201%2013.8284Z'%20fill='%238590A2'/%3e%3c/g%3e%3c/svg%3e)
Co-authors
Following
Followers
Research Focus & Metrics
Explore full metrics on Scilit
Academic Career Length
15Years (2012-Present)
(Calculated once Scilit publication data is synced: current year − year of first publication + 1)
Representative Publications
View All Publications1 July 2021 in European Journal of Pharmaceutical Sciences
Journal Article
Zahari VinarovMAMohammad Abdallah
Mohammad AbdallahJAJosé A.G. Agundez
José A.G. Agundez
Karel AllegaertABAbdul W. Basit
Abdul W. Basit
PAPatrick Augustijns
Patrick Augustijns +19
The absorption of oral drugs is frequently plagued by significant variability with potentially serious therapeutic consequences. The source of variability can be traced back to interindividual variability in physiology, differences in special populations (age- and disease-dependent), drug and formulation properties, or food-drug interactions. Clinical evidence for the impact of some of these factors on drug pharmacokinetic variability is mounting: e.g. gastric pH and emptying time, small intestinal fluid properties, differences in pediatrics and the elderly, and surgical changes in gastrointestinal anatomy. However, the link of colonic factors variability (transit time, fluid composition, microbiome), sex differences (male vs. female) and gut-related diseases (chronic constipation, anorexia and cachexia) to drug absorption variability has not been firmly established yet. At the same time, a way to decrease oral drug pharmacokinetic variability is provided by the pharmaceutical industry: clinical evidence suggests that formulation approaches employed during drug development can decrease the variability in oral exposure. This review outlines the main drivers of oral drug exposure variability and potential approaches to overcome them, while highlighting existing knowledge gaps and guiding future studies in this area.
1 September 2019 in European Journal of Pharmaceutical Sciences
Journal Article
Ben BoydCBChristel BERGSTRÖM
Christel BERGSTRÖMZahari VinarovMKMartin Kuentz
Martin KuentzJBJoachim Brouwers
Joachim BrouwersVJVincent Jannin
Vincent Jannin +7
Poorly water-soluble drugs continue to be a problematic, yet important class of pharmaceutical compounds for treatment of a wide range of diseases. Their prevalence in discovery is still high, and their development is usually limited by our lack of a complete understanding of how the complex chemical, physiological and biochemical processes that occur between administration and absorption individually and together impact on bioavailability. This review defines the challenge presented by these drugs, outlines contemporary strategies to solve this challenge, and consequent in silico and in vitro evaluation of the delivery technologies for poorly water-soluble drugs. The next steps and unmet needs are proposed to present a roadmap for future studies for the field to consider enabling progress in delivery of poorly water-soluble compounds.
30 November 2017 in Drug Development and Industrial Pharmacy
Journal Article
Zahari VinarovVKV. Katev
V. Katev
DRD. Radeva
D. Radeva
STS. Tcholakova
S. Tcholakova
Nikolai DenkovObjective: This study aims to clarify the role of surfactant and drug molecular structures on drug solubility in micellar surfactant solutions. Significance: (1) Rationale for surfactant selection is provided; (2) the large data set can be used for validation of the drug solubility parameters used in oral absorption models. Methods: Equilibrium solubility of two hydrophobic drugs and one model hydrophobic steroid in micellar solutions of 19 surfactants was measured by HPLC. The drug solubilization locus in the micelles was assessed by UV spectrometry. Results: Danazol is solubilized much more efficiently than fenofibrate by ionic surfactants due to ion–dipole interactions between the charged surfactant head groups and the polar steroid backbone. Drug solubilization increases linearly with the increase of hydrophobic chain length for all studied surfactant types. Addition of 1–3 ethylene oxide (EO) units in the head group of dodecyl sulfate surfactants reduces significantly the solubilization of both studied drugs and decreases linearly the solubilization locus polarity of fenofibrate. The locus of fenofibrate solubilization is in the hydrophobic core of nonionic surfactant micelles and in the palisade layer of ionic surfactant micelles. Conclusions: Highest drug solubility can be obtained by using surfactants molecules with long chain length coupled with hydrophilic head group that provides additional drug–surfactant interactions (i.e. ion–dipole) in the micelles.
25 November 2014 in Food & Function
Journal Article
LVLiliya Vinarova
Liliya Vinarova
Zahari VinarovVAVasil Atanasov
Vasil AtanasovIPIvayla Pantcheva
Ivayla Pantcheva
Slavka TcholakovaSSSimeon Stoyanov
Simeon Stoyanov +1
Using an in vitro digestion model, we studied the effect of six saponin extracts on the bioaccessibility of cholesterol and saturated fatty acids (SFAs). In the absence of saponins, around 78% of the available cholesterol was solubilized in the simulated intestinal fluids. The addition of two extracts, Quillaja Dry (QD) and Sapindin (SAP), was found to decrease cholesterol bioaccessibility to 19% and 44%, respectively. For both extracts, the main mechanism of this effect is the displacement of cholesterol molecules from the bile salt micelles, leading to formation of cholesterol precipitates that cannot pass through the mucus layer of the intestine. QD decreased strongly the SFA bioaccessibility as well, from 69 to 9%, due to formation of calcium-SFA precipitates, while SAP had no effect on SFA. We studied the in vivo activity of QD and SAP extracts by measuring serum cholesterol in mice fed with experimental diets within a 7-day period. Both extracts were found to prevent dietary hypercholesterolemia in mice fed on a cholesterol-rich diet. The other saponin extracts did not show any significant effect in vitro and, therefore, were not studied in vivo. The cholesterol lowering ability of Sapindin extract is reported for the first time in the current study.
1 December 2016 in Journal of Drug Delivery Science and Technology
Journal Article
KSKaterina Stoyanova
Katerina Stoyanova
Zahari VinarovSlavka Tcholakova27 April 2017 in Nature Communications
Journal Article
Slavka TcholakovaZVZhulieta Valkova
Zhulieta Valkova
DCDiana Cholakova
Diana CholakovaZahari VinarovILIvan Lesov
Ivan LesovSSStoyan K. Smoukov
Stoyan K. Smoukov +1
In self-emulsification higher-energy micrometre and sub-micrometre oil droplets are spontaneously produced from larger ones and only a few such methods are known. They usually involve a one-time reduction in oil solubility in the continuous medium via changing temperature or solvents or a phase inversion in which the preferred curvature of the interfacial surfactant layer changes its sign. Here we harness narrow-range temperature cycling to cause repeated breakup of droplets to higher-energy states. We describe three drop breakup mechanisms that lead the drops to burst spontaneously into thousands of smaller droplets. One of these mechanisms includes the remarkable phenomenon of lipid crystal dewetting from its own melt. The method works with various oil–surfactant combinations and has several important advantages. It enables low surfactant emulsion formulations with temperature-sensitive compounds, is scalable to industrial emulsification and applicable to fabricating particulate drug carriers with desired size and shape.
About Me
Zahari Vinarov has a Master’s degree in pharmacy, a PhD in Chemistry and a second PhD in Pharmaceutical sciences. He is assistant professor at Sofia University and post-doc in the group of prof. Patrick Augustijns at KU Leuven and is working on a joint project with Janssen Pharmaceutica. His main interests are in the oral delivery of poorly water-soluble drugs, drug solubilization and in vitro modelling of the GI tract, with a specific focus on the physicochemical mechanisms.
Zahari Vinarov has been involved in more than 15 industry-funded projects on the application of colloid & interface science in formulation technology. He is a member of the European Pharmacopoeia Group of Experts 13H (Fatty oils & derivatives, polymers). He is co-lead of WG 3 Advanced drug formulations and core-group member of the “European network on understanding of gastrointestinal absorption-related processes” (COST Action CA16205 UNGAP).
Zahari Vinarov is an Editorial board member of the Journal of Pharmacy and Pharmacology (Wiley/Royal Pharmaceutical Society), Topic Editor of Molecules (MDPI), Review Editor in Frontiers in Drug Delivery (Frontiers) and active reviewer for the Journal of Controlled Release (IF = 9.8), Chemical Science (IF = 9.8), Journal of colloid and interface science (IF = 8.1), Journal of materials chemistry B (IF = 6.3), Journal of molecular liquids (IF = 6.2), Molecular pharmaceutics (IF = 4.9), Langmuir (IF = 3.9), Drug delivery and industrial pharmacy (IF = 3.2).