Reversing Tumor Immunosuppressive Microenvironment via Targeting Codelivery of CpG ODNs/PD-L1 Peptide Antagonists to Enhance the Immune Checkpoint Blockade-based Anti-tumor Effect
Eur J Pharm Sci. 2021 Oct 16:106044. doi: 10.1016/j.ejps.2021.106044. Online ahead of print.ABSTRACTIn order to reverse tumor immunosuppressive microenvironment and improve antitumor immune effect based on immune checkpoint blocking, a mannose-modified liposome-based CpG ODNs and PD-L1 antagonistic peptides (P) co-delivery system (HA/M-Lipo CpG-P) was constructed, in which hyaluronic acid (HA) coating was supposed to improve the systemic circulation stability and thereby promote its accumulation in tumor tissues. When the HA/M-Lipo CpG-P complexes enter the tumor tissues, HA will be hydrolyzed under the action of hyaluroni...
Source: European Journal of Pharmaceutical Sciences - October 19, 2021 Category: Drugs & Pharmacology Authors: Min Zhang Zhou Fang Haitao Zhang Mingxiao Cui Mingfu Wang Kehai Liu Source Type: research

Peptide Conjugates of 18 β-Glycyrrhetinic Acid as Potent Inhibitors of α-Glucosidase and AGEs-Induced Oxidation
In conclusion, our data demonstrates that besides possessing strong α-glucosidase inhibition, the peptide conjugates also alleviated the AGEs-induced NO• production in RAW macrophages. Dual inhibition of α-glucosidase enzyme, and AGEs-induced NO• production by 18β-GA-peptide conjugates pave the way for further research in anti-diabetic drug discovery.PMID:34666184 | DOI:10.1016/j.ejps.2021.106045 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - October 19, 2021 Category: Drugs & Pharmacology Authors: Sadiq Noor Khan Farzana Shaheen Umair Aleem Sumbla Farooq Sheikh Alfred Ngenge Tamfu Sajda Ashraf Zaheer Ul-Haq Saeed Ullah Atia-Tul- Wahab M Iqbal Choudhary Humera Jahan Source Type: research

UNGAP best practice for improving solubility data quality of orally administered drugs
Eur J Pharm Sci. 2021 Oct 15:106043. doi: 10.1016/j.ejps.2021.106043. Online ahead of print.ABSTRACTAn important goal of the European Cooperation in Science and Technology (COST) Action UNGAP (UNderstanding Gastrointestinal Absorption-related Processes, www.ungap.eu) is to improve standardization of methods relating to the study of oral drug absorption. Solubility is a general term that refers to the maximum achievable concentration of a compound dissolved in a liquid medium. For orally administered drugs, relevant information on drug properties is crucial during drug (product) development and at the regulatory level. Coll...
Source: European Journal of Pharmaceutical Sciences - October 18, 2021 Category: Drugs & Pharmacology Authors: M Vertzoni J Alsenz P Augustijns A Bauer-Brandl Cas Bergstr öm J Brouwers A M üllerz G Perlovich C Saal K Sugano C Reppas Source Type: research

UNGAP best practice for improving solubility data quality of orally administered drugs
Eur J Pharm Sci. 2021 Oct 15:106043. doi: 10.1016/j.ejps.2021.106043. Online ahead of print.ABSTRACTAn important goal of the European Cooperation in Science and Technology (COST) Action UNGAP (UNderstanding Gastrointestinal Absorption-related Processes, www.ungap.eu) is to improve standardization of methods relating to the study of oral drug absorption. Solubility is a general term that refers to the maximum achievable concentration of a compound dissolved in a liquid medium. For orally administered drugs, relevant information on drug properties is crucial during drug (product) development and at the regulatory level. Coll...
Source: European Journal of Pharmaceutical Sciences - October 18, 2021 Category: Drugs & Pharmacology Authors: M Vertzoni J Alsenz P Augustijns A Bauer-Brandl Cas Bergstr öm J Brouwers A M üllerz G Perlovich C Saal K Sugano C Reppas Source Type: research

Influence of release rate, dose and co-administration on pharmacokinetics, pharmacodynamics and PK-PD relationship of tanshinone IIA and tanshinol
Eur J Pharm Sci. 2021 Oct 14:106042. doi: 10.1016/j.ejps.2021.106042. Online ahead of print.ABSTRACTThe present study aims to investigate the influence of release rate, dose and co-administration on pharmacokinetics (PK) and pharmacodynamics (PD) of tanshinone IIA (TA) and tanshinol (TS), and reveal the changes in their PK-PD relationships. Sustained and immediate release pellets of TS and TA were prepared respectively, and oral administrated to angina model rabbits according to the experimental design. The administration dose of TS was 50, 35 or 20 mg/kg and that of TA was 30 mg/kg. Then, plasma concentrations of TS and T...
Source: European Journal of Pharmaceutical Sciences - October 17, 2021 Category: Drugs & Pharmacology Authors: Zhenghua Li Ziyi Li Bingwei Wang Jianping Liu Source Type: research

Dissolving microneedle-assisted long-acting Liraglutide delivery to control type 2 diabetes and obesity
In this study, the capacity of 2 kinds of 500 μm and 1000 μm needles to deliver the desired dose of drug was obtained based on experimental and mathematical methods.PMID:34655736 | DOI:10.1016/j.ejps.2021.106040 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - October 16, 2021 Category: Drugs & Pharmacology Authors: Morteza Rabiei Soheila Kashanian Gholamreza Bahrami Hossein Derakhshankhah Ebrahim Barzegari Seyedeh Sabereh Samavati Steven J P McInnes Source Type: research

Chitosan/ β-glycerophosphate in situ forming thermo-sensitive hydrogel for improved ocular delivery of moxifloxacin hydrochloride
Eur J Pharm Sci. 2021 Oct 13:106041. doi: 10.1016/j.ejps.2021.106041. Online ahead of print.ABSTRACTThe aim of the current work is to develop a thermo-sensitive hydrogel system of moxifloxacin hydrochloride (MOX) for improved ocular delivery. Fifteen formulations were prepared at different concentrations of β-glycerophosphate disodium salt (β-GP) 12-20% (w/v) and chitosan (CS) 1.7-1.9% (w/v). MOX loaded optimized thermo-sensitive hydrogel system (F8), consisting of CS (1.8%, w/v) and β-GP (16%, w/v), showed optimum gelation temperature (35°C) and gelation time (2 min), thus selected for further investiga...
Source: European Journal of Pharmaceutical Sciences - October 16, 2021 Category: Drugs & Pharmacology Authors: Marwa Hasanein Asfour Sameh Hosam Abd El-Alim Ghada Elsayed Ahmed Awad Ahmed Alaa Kassem Source Type: research

Dissolving microneedle-assisted long-acting Liraglutide delivery to control type 2 diabetes and obesity
In this study, the capacity of 2 kinds of 500 μm and 1000 μm needles to deliver the desired dose of drug was obtained based on experimental and mathematical methods.PMID:34655736 | DOI:10.1016/j.ejps.2021.106040 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - October 16, 2021 Category: Drugs & Pharmacology Authors: Morteza Rabiei Soheila Kashanian Gholamreza Bahrami Hossein Derakhshankhah Ebrahim Barzegari Seyedeh Sabereh Samavati Steven J P McInnes Source Type: research

Chitosan/ β-glycerophosphate in situ forming thermo-sensitive hydrogel for improved ocular delivery of moxifloxacin hydrochloride
Eur J Pharm Sci. 2021 Oct 13:106041. doi: 10.1016/j.ejps.2021.106041. Online ahead of print.ABSTRACTThe aim of the current work is to develop a thermo-sensitive hydrogel system of moxifloxacin hydrochloride (MOX) for improved ocular delivery. Fifteen formulations were prepared at different concentrations of β-glycerophosphate disodium salt (β-GP) 12-20% (w/v) and chitosan (CS) 1.7-1.9% (w/v). MOX loaded optimized thermo-sensitive hydrogel system (F8), consisting of CS (1.8%, w/v) and β-GP (16%, w/v), showed optimum gelation temperature (35°C) and gelation time (2 min), thus selected for further investiga...
Source: European Journal of Pharmaceutical Sciences - October 16, 2021 Category: Drugs & Pharmacology Authors: Marwa Hasanein Asfour Sameh Hosam Abd El-Alim Ghada Elsayed Ahmed Awad Ahmed Alaa Kassem Source Type: research

Explicating the molecular level drug-polymer interactions at the interface of supersaturated solution of the model drug: Albendazole
Eur J Pharm Sci. 2021 Oct 10:106014. doi: 10.1016/j.ejps.2021.106014. Online ahead of print.ABSTRACTSupersaturation phenomenon addresses aqueous solubility of poorly water soluble drugs. However, supersaturation state of drugs tends to crystallize because of its thermodynamic instability thereby compromising the solubility and biopharmaceutical performance of drugs. The present study aims to investigate the supersaturation potential of albendazole (ABZ) and its precipitation via nucleation and crystal growth. We hypothesized the use of polymers as precipitation inhibitors and drug polymer interactions are characterized usi...
Source: European Journal of Pharmaceutical Sciences - October 13, 2021 Category: Drugs & Pharmacology Authors: Prachi Joshi Prabhakar Mallepogu Harpreet Kaur Ridhima Singh Ikjot Sodhi Sanjaya K Samal Kailash C Jena Abhay T Sangamwar Source Type: research

Stability of high concentrated triple intrathecal therapy for pediatrics and mitigation strategies
Eur J Pharm Sci. 2021 Oct 10:106039. doi: 10.1016/j.ejps.2021.106039. Online ahead of print.ABSTRACTStringent formulation requirements are defined to intrathecally administer drug substances, avoiding neurological complications. In case of pediatric patients, these are further complicated due to the limited volumes of the celebrospinal fluid and, therefore, high concentrated solutions of methotrexate (MTX), cytarabine and corticosteroids (i.e., methylprednisolone or hydrocortisone) are prepared based on the patient's age. This work aims to assess the chemical and physical stability of triple intrathecal mixtures differing ...
Source: European Journal of Pharmaceutical Sciences - October 13, 2021 Category: Drugs & Pharmacology Authors: Davide Zanon Francesca Selmin Giorgio Centin Natalia Maximova Antonella Casiraghi Paola Minghetti Source Type: research

Explicating the molecular level drug-polymer interactions at the interface of supersaturated solution of the model drug: Albendazole
Eur J Pharm Sci. 2021 Oct 10:106014. doi: 10.1016/j.ejps.2021.106014. Online ahead of print.ABSTRACTSupersaturation phenomenon addresses aqueous solubility of poorly water soluble drugs. However, supersaturation state of drugs tends to crystallize because of its thermodynamic instability thereby compromising the solubility and biopharmaceutical performance of drugs. The present study aims to investigate the supersaturation potential of albendazole (ABZ) and its precipitation via nucleation and crystal growth. We hypothesized the use of polymers as precipitation inhibitors and drug polymer interactions are characterized usi...
Source: European Journal of Pharmaceutical Sciences - October 13, 2021 Category: Drugs & Pharmacology Authors: Prachi Joshi Prabhakar Mallepogu Harpreet Kaur Ridhima Singh Ikjot Sodhi Sanjaya K Samal Kailash C Jena Abhay T Sangamwar Source Type: research

Stability of high concentrated triple intrathecal therapy for pediatrics and mitigation strategies
Eur J Pharm Sci. 2021 Oct 10:106039. doi: 10.1016/j.ejps.2021.106039. Online ahead of print.ABSTRACTStringent formulation requirements are defined to intrathecally administer drug substances, avoiding neurological complications. In case of pediatric patients, these are further complicated due to the limited volumes of the celebrospinal fluid and, therefore, high concentrated solutions of methotrexate (MTX), cytarabine and corticosteroids (i.e., methylprednisolone or hydrocortisone) are prepared based on the patient's age. This work aims to assess the chemical and physical stability of triple intrathecal mixtures differing ...
Source: European Journal of Pharmaceutical Sciences - October 13, 2021 Category: Drugs & Pharmacology Authors: Davide Zanon Francesca Selmin Giorgio Centin Natalia Maximova Antonella Casiraghi Paola Minghetti Source Type: research

Explicating the molecular level drug-polymer interactions at the interface of supersaturated solution of the model drug: Albendazole
Eur J Pharm Sci. 2021 Oct 10:106014. doi: 10.1016/j.ejps.2021.106014. Online ahead of print.ABSTRACTSupersaturation phenomenon addresses aqueous solubility of poorly water soluble drugs. However, supersaturation state of drugs tends to crystallize because of its thermodynamic instability thereby compromising the solubility and biopharmaceutical performance of drugs. The present study aims to investigate the supersaturation potential of albendazole (ABZ) and its precipitation via nucleation and crystal growth. We hypothesized the use of polymers as precipitation inhibitors and drug polymer interactions are characterized usi...
Source: European Journal of Pharmaceutical Sciences - October 13, 2021 Category: Drugs & Pharmacology Authors: Prachi Joshi Prabhakar Mallepogu Harpreet Kaur Ridhima Singh Ikjot Sodhi Sanjaya K Samal Kailash C Jena Abhay T Sangamwar Source Type: research

Stability of high concentrated triple intrathecal therapy for pediatrics and mitigation strategies
Eur J Pharm Sci. 2021 Oct 10:106039. doi: 10.1016/j.ejps.2021.106039. Online ahead of print.ABSTRACTStringent formulation requirements are defined to intrathecally administer drug substances, avoiding neurological complications. In case of pediatric patients, these are further complicated due to the limited volumes of the celebrospinal fluid and, therefore, high concentrated solutions of methotrexate (MTX), cytarabine and corticosteroids (i.e., methylprednisolone or hydrocortisone) are prepared based on the patient's age. This work aims to assess the chemical and physical stability of triple intrathecal mixtures differing ...
Source: European Journal of Pharmaceutical Sciences - October 13, 2021 Category: Drugs & Pharmacology Authors: Davide Zanon Francesca Selmin Giorgio Centin Natalia Maximova Antonella Casiraghi Paola Minghetti Source Type: research

Enteric complex layer-coated controlled release of capsaicin from phytosterol/ γ-cyclodextrin microparticles via guest exchange reaction with taurocholic acid
Eur J Pharm Sci. 2021 Oct 9:106038. doi: 10.1016/j.ejps.2021.106038. Online ahead of print.ABSTRACTPhytosterol (PSE)/γ-cyclodextrin (γ-CD) microparticles have a capsule-like structure, wherein the hydrophobic PSE core is surrounded by outer layers of the hydrophilic PSE/γ-CD inclusion complex crystal. The microparticles could mask the undesirable taste of capsaicin (CAP) by encapsulation of CAP into the microparticles. In the present study, the dissolution of CAP from PSE/γ-CD microparticles into artificial intestinal fluids was examined using the paddle method. The dissolution of CAP from the micro...
Source: European Journal of Pharmaceutical Sciences - October 12, 2021 Category: Drugs & Pharmacology Authors: Hiroshi Sasako Kazuo Koyama Kenjirou Higashi Keisuke Ueda Arisa Ishimoto Kunikazu Moribe Source Type: research

Amorphous solid dispersions of cyclosporine A with improved bioavailability prepared via hot melt extrusion: formulation, physicochemical characterization, and in vivo evaluation
This study had a reference value for the bioavailability improvement of oral CsA preparations.PMID:34637896 | DOI:10.1016/j.ejps.2021.106036 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - October 12, 2021 Category: Drugs & Pharmacology Authors: Xinxin Jiang Yanna Zhao Qingran Guan Shanshan Xiao Weimiao Dong Shipeng Lian Huaizhen Zhang Min Liu Zhengping Wang Jun Han Source Type: research

Is equilibrium slurry pH a good surrogate for solid surface pH during drug dissolution?
Eur J Pharm Sci. 2021 Oct 9:106037. doi: 10.1016/j.ejps.2021.106037. Online ahead of print.ABSTRACTThe purpose of the present study was to investigate the suitability of equilibrium slurry pH (pHeq) as a surrogate of solid surface pH during drug dissolution (pH0). A comprehensive calculation scheme for pHeq and pH0 was formalized based on the principle of charge neutrality (equilibrium charge neutrality for pHeq and charge flux neutrality for pH0). The formalized scheme was then used to investigate the validity of pH0 ≈ pHeq approximation. The approximation of pH0 ≈ pHeq was suggested to be accurate for small m...
Source: European Journal of Pharmaceutical Sciences - October 12, 2021 Category: Drugs & Pharmacology Authors: Taiga Uekusa Alex Avdeef Kiyohiko Sugano Source Type: research

Enteric complex layer-coated controlled release of capsaicin from phytosterol/ γ-cyclodextrin microparticles via guest exchange reaction with taurocholic acid
Eur J Pharm Sci. 2021 Oct 9:106038. doi: 10.1016/j.ejps.2021.106038. Online ahead of print.ABSTRACTPhytosterol (PSE)/γ-cyclodextrin (γ-CD) microparticles have a capsule-like structure, wherein the hydrophobic PSE core is surrounded by outer layers of the hydrophilic PSE/γ-CD inclusion complex crystal. The microparticles could mask the undesirable taste of capsaicin (CAP) by encapsulation of CAP into the microparticles. In the present study, the dissolution of CAP from PSE/γ-CD microparticles into artificial intestinal fluids was examined using the paddle method. The dissolution of CAP from the micro...
Source: European Journal of Pharmaceutical Sciences - October 12, 2021 Category: Drugs & Pharmacology Authors: Hiroshi Sasako Kazuo Koyama Kenjirou Higashi Keisuke Ueda Arisa Ishimoto Kunikazu Moribe Source Type: research

Amorphous solid dispersions of cyclosporine A with improved bioavailability prepared via hot melt extrusion: formulation, physicochemical characterization, and in vivo evaluation
This study had a reference value for the bioavailability improvement of oral CsA preparations.PMID:34637896 | DOI:10.1016/j.ejps.2021.106036 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - October 12, 2021 Category: Drugs & Pharmacology Authors: Xinxin Jiang Yanna Zhao Qingran Guan Shanshan Xiao Weimiao Dong Shipeng Lian Huaizhen Zhang Min Liu Zhengping Wang Jun Han Source Type: research

Is equilibrium slurry pH a good surrogate for solid surface pH during drug dissolution?
Eur J Pharm Sci. 2021 Oct 9:106037. doi: 10.1016/j.ejps.2021.106037. Online ahead of print.ABSTRACTThe purpose of the present study was to investigate the suitability of equilibrium slurry pH (pHeq) as a surrogate of solid surface pH during drug dissolution (pH0). A comprehensive calculation scheme for pHeq and pH0 was formalized based on the principle of charge neutrality (equilibrium charge neutrality for pHeq and charge flux neutrality for pH0). The formalized scheme was then used to investigate the validity of pH0 ≈ pHeq approximation. The approximation of pH0 ≈ pHeq was suggested to be accurate for small m...
Source: European Journal of Pharmaceutical Sciences - October 12, 2021 Category: Drugs & Pharmacology Authors: Taiga Uekusa Alex Avdeef Kiyohiko Sugano Source Type: research

Study of rheological and tableting properties of lubricated mixtures of co-processed dry binders for orally disintegrating tablets
Eur J Pharm Sci. 2021 Oct 8:106035. doi: 10.1016/j.ejps.2021.106035. Online ahead of print.ABSTRACTCo-processed dry binders for ODTs are important multifunctional excipients for tablet manufacturing by direct compression. Testing their binary mixtures with lubricants is an important aspect of their use in combination with drugs. The aim of this study was to evaluate the rheological and compression properties of lubricated mixtures of co-processed dry binders Parteck® ODT, Prosolv® ODT G2 and Ludiflash®, and subsequently also the compactability and disintegration time of the tablets made thereof. The lubricants ...
Source: European Journal of Pharmaceutical Sciences - October 11, 2021 Category: Drugs & Pharmacology Authors: Thao Tranov á Oliver Macho Jan Loskot Jitka Mu žíková Source Type: research

On the usefulness of four in vitro methods in assessing the intraluminal performance of poorly soluble, ionisable compounds in the fasted state
Eur J Pharm Sci. 2021 Oct 7:106034. doi: 10.1016/j.ejps.2021.106034. Online ahead of print.ABSTRACTA small-scale two-stage biphasic system, a small-scale two-stage dissolution-permeation system, the Erweka mini-paddle apparatus, and the BioGIT system were evaluated for their usefulness in assessing the intraluminal performance of two low solubility drugs in the fasted state, one with weakly acidic properties (tested in a salt form, diclofenac potassium) and one with weakly alkaline properties [ritonavir, tested as an amorphous solid dispersion (ASD)]. In all in vitro methods, an immediate-release tablet and a powder formul...
Source: European Journal of Pharmaceutical Sciences - October 10, 2021 Category: Drugs & Pharmacology Authors: Patrick J O'Dwyer Karl J Box Georgios Imanidis Maria Vertzoni Christos Reppas Source Type: research

On the usefulness of four in vitro methods in assessing the intraluminal performance of poorly soluble, ionisable compounds in the fasted state
Eur J Pharm Sci. 2021 Oct 7:106034. doi: 10.1016/j.ejps.2021.106034. Online ahead of print.ABSTRACTA small-scale two-stage biphasic system, a small-scale two-stage dissolution-permeation system, the Erweka mini-paddle apparatus, and the BioGIT system were evaluated for their usefulness in assessing the intraluminal performance of two low solubility drugs in the fasted state, one with weakly acidic properties (tested in a salt form, diclofenac potassium) and one with weakly alkaline properties [ritonavir, tested as an amorphous solid dispersion (ASD)]. In all in vitro methods, an immediate-release tablet and a powder formul...
Source: European Journal of Pharmaceutical Sciences - October 10, 2021 Category: Drugs & Pharmacology Authors: Patrick J O'Dwyer Karl J Box Georgios Imanidis Maria Vertzoni Christos Reppas Source Type: research

Structure identification of circulating metabolites from somapacitan, a long-acting growth hormone derivative, and pharmacokinetics after single and multiple subcutaneous dosing in rats
This study has provided non-clinical safety data that contribute to an overall safety assessment of somapacitan.PMID:34610450 | DOI:10.1016/j.ejps.2021.106032 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - October 5, 2021 Category: Drugs & Pharmacology Authors: Hans Helleberg Rikke Hvid Lindecrona Peter Thygesen Mads Bjelke Source Type: research

Towards prevention of ischemia-reperfusion kidney injury: Pre-clinical evaluation of 6-chromanol derivatives and the lead compound SUL-138
Eur J Pharm Sci. 2021 Oct 2:106033. doi: 10.1016/j.ejps.2021.106033. Online ahead of print.ABSTRACTAcute Kidney Injury (AKI) is a global healthcare burden attributable to high mortality and staggering costs of dialysis. The underlying causes of AKI include hypothermia and rewarming (H/R), ischemia/reperfusion (I/R), mitochondrial dysfunction and reactive oxygen species production. Inspired by the mechanisms conferring organ protection in hibernating hamster, 6-chromanol derived compounds were developed to address the need of effective prevention and treatment of AKI. Here we report on the pre-clinical screening of 6-chroma...
Source: European Journal of Pharmaceutical Sciences - October 5, 2021 Category: Drugs & Pharmacology Authors: P C Vogelaar D Nakladal D H Swart Ľ Tkáčiková S Tk áčiková A C van der Graaf R H Henning G Krenning Source Type: research

Structure identification of circulating metabolites from somapacitan, a long-acting growth hormone derivative, and pharmacokinetics after single and multiple subcutaneous dosing in rats
This study has provided non-clinical safety data that contribute to an overall safety assessment of somapacitan.PMID:34610450 | DOI:10.1016/j.ejps.2021.106032 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - October 5, 2021 Category: Drugs & Pharmacology Authors: Hans Helleberg Rikke Hvid Lindecrona Peter Thygesen Mads Bjelke Source Type: research

Towards prevention of ischemia-reperfusion kidney injury: Pre-clinical evaluation of 6-chromanol derivatives and the lead compound SUL-138
Eur J Pharm Sci. 2021 Oct 2:106033. doi: 10.1016/j.ejps.2021.106033. Online ahead of print.ABSTRACTAcute Kidney Injury (AKI) is a global healthcare burden attributable to high mortality and staggering costs of dialysis. The underlying causes of AKI include hypothermia and rewarming (H/R), ischemia/reperfusion (I/R), mitochondrial dysfunction and reactive oxygen species production. Inspired by the mechanisms conferring organ protection in hibernating hamster, 6-chromanol derived compounds were developed to address the need of effective prevention and treatment of AKI. Here we report on the pre-clinical screening of 6-chroma...
Source: European Journal of Pharmaceutical Sciences - October 5, 2021 Category: Drugs & Pharmacology Authors: P C Vogelaar D Nakladal D H Swart Ľ Tkáčiková S Tk áčiková A C van der Graaf R H Henning G Krenning Source Type: research

Structure identification of circulating metabolites from somapacitan, a long-acting growth hormone derivative, and pharmacokinetics after single and multiple subcutaneous dosing in rats
This study has provided non-clinical safety data that contribute to an overall safety assessment of somapacitan.PMID:34610450 | DOI:10.1016/j.ejps.2021.106032 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - October 5, 2021 Category: Drugs & Pharmacology Authors: Hans Helleberg Rikke Hvid Lindecrona Peter Thygesen Mads Bjelke Source Type: research

Towards prevention of ischemia-reperfusion kidney injury: Pre-clinical evaluation of 6-chromanol derivatives and the lead compound SUL-138
Eur J Pharm Sci. 2021 Oct 2:106033. doi: 10.1016/j.ejps.2021.106033. Online ahead of print.ABSTRACTAcute Kidney Injury (AKI) is a global healthcare burden attributable to high mortality and staggering costs of dialysis. The underlying causes of AKI include hypothermia and rewarming (H/R), ischemia/reperfusion (I/R), mitochondrial dysfunction and reactive oxygen species production. Inspired by the mechanisms conferring organ protection in hibernating hamster, 6-chromanol derived compounds were developed to address the need of effective prevention and treatment of AKI. Here we report on the pre-clinical screening of 6-chroma...
Source: European Journal of Pharmaceutical Sciences - October 5, 2021 Category: Drugs & Pharmacology Authors: P C Vogelaar D Nakladal D H Swart Ľ Tkáčiková S Tk áčiková A C van der Graaf R H Henning G Krenning Source Type: research

Structure identification of circulating metabolites from somapacitan, a long-acting growth hormone derivative, and pharmacokinetics after single and multiple subcutaneous dosing in rats
This study has provided non-clinical safety data that contribute to an overall safety assessment of somapacitan.PMID:34610450 | DOI:10.1016/j.ejps.2021.106032 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - October 5, 2021 Category: Drugs & Pharmacology Authors: Hans Helleberg Rikke Hvid Lindecrona Peter Thygesen Mads Bjelke Source Type: research

Towards prevention of ischemia-reperfusion kidney injury: Pre-clinical evaluation of 6-chromanol derivatives and the lead compound SUL-138
Eur J Pharm Sci. 2021 Oct 2:106033. doi: 10.1016/j.ejps.2021.106033. Online ahead of print.ABSTRACTAcute Kidney Injury (AKI) is a global healthcare burden attributable to high mortality and staggering costs of dialysis. The underlying causes of AKI include hypothermia and rewarming (H/R), ischemia/reperfusion (I/R), mitochondrial dysfunction and reactive oxygen species production. Inspired by the mechanisms conferring organ protection in hibernating hamster, 6-chromanol derived compounds were developed to address the need of effective prevention and treatment of AKI. Here we report on the pre-clinical screening of 6-chroma...
Source: European Journal of Pharmaceutical Sciences - October 5, 2021 Category: Drugs & Pharmacology Authors: P C Vogelaar D Nakladal D H Swart Ľ Tkáčiková S Tk áčiková A C van der Graaf R H Henning G Krenning Source Type: research

Structure identification of circulating metabolites from somapacitan, a long-acting growth hormone derivative, and pharmacokinetics after single and multiple subcutaneous dosing in rats
This study has provided non-clinical safety data that contribute to an overall safety assessment of somapacitan.PMID:34610450 | DOI:10.1016/j.ejps.2021.106032 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - October 5, 2021 Category: Drugs & Pharmacology Authors: Hans Helleberg Rikke Hvid Lindecrona Peter Thygesen Mads Bjelke Source Type: research

Towards prevention of ischemia-reperfusion kidney injury: Pre-clinical evaluation of 6-chromanol derivatives and the lead compound SUL-138
Eur J Pharm Sci. 2021 Oct 2:106033. doi: 10.1016/j.ejps.2021.106033. Online ahead of print.ABSTRACTAcute Kidney Injury (AKI) is a global healthcare burden attributable to high mortality and staggering costs of dialysis. The underlying causes of AKI include hypothermia and rewarming (H/R), ischemia/reperfusion (I/R), mitochondrial dysfunction and reactive oxygen species production. Inspired by the mechanisms conferring organ protection in hibernating hamster, 6-chromanol derived compounds were developed to address the need of effective prevention and treatment of AKI. Here we report on the pre-clinical screening of 6-chroma...
Source: European Journal of Pharmaceutical Sciences - October 5, 2021 Category: Drugs & Pharmacology Authors: P C Vogelaar D Nakladal D H Swart Ľ Tkáčiková S Tk áčiková A C van der Graaf R H Henning G Krenning Source Type: research

Tailoring the Proliferation of Fibroblast Cells by Multiresponsive and Thermosensitive Stem Cells Composite F127 Hydrogel Containing Folic acid.MgO:ZnO/chitosan Hybrid Microparticles for Skin Regeneration
In this study, biodegradable and thermosensitive F127 hydrogel containing folic acid.MgO:ZnO/chitosan hybrid particles (FMZC) were fabricated as a 3D mesenchymal stem cells (MSCs) delivery vehicle for regenerative medicine and wound healing purposes, in such a way to be responsive to lysozyme and UVA irradiation. The results showed that F127 hydrogel containing FMZC is a suitable and nontoxic construct for encapsulation of MSCs in the presence of lysozyme and UVA irradiation, bearing high stem cell viability and proliferation. The final hydrogel, MSC&FMZC, in response to lysozyme induced a higher proliferation rate and...
Source: European Journal of Pharmaceutical Sciences - October 3, 2021 Category: Drugs & Pharmacology Authors: Malihe Rafie Azadeh Meshkini Source Type: research

Glycyrrhiza acid micelles loaded with licochalcone A for topical delivery: co-penetration and anti-melanogenic effect
Eur J Pharm Sci. 2021 Sep 30:106029. doi: 10.1016/j.ejps.2021.106029. Online ahead of print.ABSTRACTThe co-penetration of micellar vehicles and the encapsulated drugs into the skin layers, as well as the mechanisms underlying the penetration enhancement have not been clearly elucidated. We developed licochalcone A (LA)-loaded glycyrrhiza acid (GA) (GA+LA) micelles for topical delivery of LA into the epidermis. The in vitro release, in vitro co-penetration, penetration pathways, mechanism of interaction between skin and the micelles, and the in vitro and in vivo whitening effect of GA+LA micelles were evaluated. Co-penetrat...
Source: European Journal of Pharmaceutical Sciences - October 3, 2021 Category: Drugs & Pharmacology Authors: Zhuxian Wang Yaqi Xue Tingting Chen Qunqun Du Zhaoming Zhu Yuan Wang Yufang Wu Quanfu Zeng Chunyan Shen Cuiping Jiang Zhijun Yang Hongxia Zhu Li Liu Qiang Liu Source Type: research

Determination of effective concentrations of drug absorption enhancers using in vitro and ex vivo models
CONCLUSION: Incorporation of the drug absorption enhancers (e.g., curcumin and quercetin), at specific concentrations, in dosage forms could improve the bioavailability of the BCS Class III and IV drugs that are substrates of CYP3A4 and p-glycoprotein.PMID:34601070 | DOI:10.1016/j.ejps.2021.106028 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - October 3, 2021 Category: Drugs & Pharmacology Authors: Poloko Stephen Kheoane Gillian Mary-Anne Enslin Clemence Tarirai Source Type: research

Absorption, metabolism and excretion of once-weekly somapacitan, a long-acting growth hormone derivative, after single subcutaneous dosing in human subjects
This study (ClinicalTrials.gov, NCT02962440) investigated the absorption, metabolism and excretion, as well as the pharmacokinetics (PK), of tritium-labelled [3H]-somapacitan. Seven healthy males received a single subcutaneous dose of 6 mg somapacitan containing [3H]-somapacitan 20 MBq. Blood, serum, plasma, urine, faeces, and expired air were collected for radioactivity assessment. Metabolites were identified and quantified in plasma and urine collected. The PK of plasma components were determined, and the radioactive peaks of the most abundant plasma metabolites and urine metabolites were selected for analysis. Twenty-ei...
Source: European Journal of Pharmaceutical Sciences - October 3, 2021 Category: Drugs & Pharmacology Authors: Hans Helleberg Mads Bjelke Birgitte Bentz Damholt Palle Jacob Pedersen Michael H øjby Rasmussen Source Type: research

Tailoring the Proliferation of Fibroblast Cells by Multiresponsive and Thermosensitive Stem Cells Composite F127 Hydrogel Containing Folic acid.MgO:ZnO/chitosan Hybrid Microparticles for Skin Regeneration
In this study, biodegradable and thermosensitive F127 hydrogel containing folic acid.MgO:ZnO/chitosan hybrid particles (FMZC) were fabricated as a 3D mesenchymal stem cells (MSCs) delivery vehicle for regenerative medicine and wound healing purposes, in such a way to be responsive to lysozyme and UVA irradiation. The results showed that F127 hydrogel containing FMZC is a suitable and nontoxic construct for encapsulation of MSCs in the presence of lysozyme and UVA irradiation, bearing high stem cell viability and proliferation. The final hydrogel, MSC&FMZC, in response to lysozyme induced a higher proliferation rate and...
Source: European Journal of Pharmaceutical Sciences - October 3, 2021 Category: Drugs & Pharmacology Authors: Malihe Rafie Azadeh Meshkini Source Type: research

Glycyrrhiza acid micelles loaded with licochalcone A for topical delivery: co-penetration and anti-melanogenic effect
Eur J Pharm Sci. 2021 Sep 30:106029. doi: 10.1016/j.ejps.2021.106029. Online ahead of print.ABSTRACTThe co-penetration of micellar vehicles and the encapsulated drugs into the skin layers, as well as the mechanisms underlying the penetration enhancement have not been clearly elucidated. We developed licochalcone A (LA)-loaded glycyrrhiza acid (GA) (GA+LA) micelles for topical delivery of LA into the epidermis. The in vitro release, in vitro co-penetration, penetration pathways, mechanism of interaction between skin and the micelles, and the in vitro and in vivo whitening effect of GA+LA micelles were evaluated. Co-penetrat...
Source: European Journal of Pharmaceutical Sciences - October 3, 2021 Category: Drugs & Pharmacology Authors: Zhuxian Wang Yaqi Xue Tingting Chen Qunqun Du Zhaoming Zhu Yuan Wang Yufang Wu Quanfu Zeng Chunyan Shen Cuiping Jiang Zhijun Yang Hongxia Zhu Li Liu Qiang Liu Source Type: research

Determination of effective concentrations of drug absorption enhancers using in vitro and ex vivo models
CONCLUSION: Incorporation of the drug absorption enhancers (e.g., curcumin and quercetin), at specific concentrations, in dosage forms could improve the bioavailability of the BCS Class III and IV drugs that are substrates of CYP3A4 and p-glycoprotein.PMID:34601070 | DOI:10.1016/j.ejps.2021.106028 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - October 3, 2021 Category: Drugs & Pharmacology Authors: Poloko Stephen Kheoane Gillian Mary-Anne Enslin Clemence Tarirai Source Type: research

Absorption, metabolism and excretion of once-weekly somapacitan, a long-acting growth hormone derivative, after single subcutaneous dosing in human subjects
This study (ClinicalTrials.gov, NCT02962440) investigated the absorption, metabolism and excretion, as well as the pharmacokinetics (PK), of tritium-labelled [3H]-somapacitan. Seven healthy males received a single subcutaneous dose of 6 mg somapacitan containing [3H]-somapacitan 20 MBq. Blood, serum, plasma, urine, faeces, and expired air were collected for radioactivity assessment. Metabolites were identified and quantified in plasma and urine collected. The PK of plasma components were determined, and the radioactive peaks of the most abundant plasma metabolites and urine metabolites were selected for analysis. Twenty-ei...
Source: European Journal of Pharmaceutical Sciences - October 3, 2021 Category: Drugs & Pharmacology Authors: Hans Helleberg Mads Bjelke Birgitte Bentz Damholt Palle Jacob Pedersen Michael H øjby Rasmussen Source Type: research

Assessment of Epinephrine Sublingual Stability and Permeability Pathways to Enhance Its Permeability for the Treatment of Anaphylaxis
Eur J Pharm Sci. 2021 Sep 29:106025. doi: 10.1016/j.ejps.2021.106025. Online ahead of print.ABSTRACTPrompt epinephrine (Epi) injection using auto-injectors is the initial life-saving out-of-hospital treatment for anaphylaxis. However, patients and healthcare providers are eagerly awaiting a more convenient alternative dosage form that would overcome auto-injectors drawbacks. Previously, we extensively evaluated multiple alternative fast-disintegrating sublingual Epi tablet (FDSTs) formulations. However, the sublingual stability of Epi and effect of modifying the sublingual microenvironment pH on its stability and transport...
Source: European Journal of Pharmaceutical Sciences - October 2, 2021 Category: Drugs & Pharmacology Authors: Mutasem Rawas-Qalaji Rawan Bafail Roberta Cagliani Mohamed Haider Zahid Hussain Source Type: research

Assessment of Epinephrine Sublingual Stability and Permeability Pathways to Enhance Its Permeability for the Treatment of Anaphylaxis
Eur J Pharm Sci. 2021 Sep 29:106025. doi: 10.1016/j.ejps.2021.106025. Online ahead of print.ABSTRACTPrompt epinephrine (Epi) injection using auto-injectors is the initial life-saving out-of-hospital treatment for anaphylaxis. However, patients and healthcare providers are eagerly awaiting a more convenient alternative dosage form that would overcome auto-injectors drawbacks. Previously, we extensively evaluated multiple alternative fast-disintegrating sublingual Epi tablet (FDSTs) formulations. However, the sublingual stability of Epi and effect of modifying the sublingual microenvironment pH on its stability and transport...
Source: European Journal of Pharmaceutical Sciences - October 2, 2021 Category: Drugs & Pharmacology Authors: Mutasem Rawas-Qalaji Rawan Bafail Roberta Cagliani Mohamed Haider Zahid Hussain Source Type: research

NDMA Analytics in Metformin Products: Comparison of Methods and Pitfalls
CONCLUSION: Metformin pharmaceuticals contain traces of the API impurity DMA as well as inorganic nitrite from excipients. This can lead to artefactual formation of NDMA and hence false positive results if DCM is used for sample extraction. Similar artefacts are likely also in other pharmaceuticals if these contain the secondary amine precursor of the respective nitrosamine analyte.PMID:34597792 | DOI:10.1016/j.ejps.2021.106026 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - October 1, 2021 Category: Drugs & Pharmacology Authors: Matthias Fritzsche Giorgio Blom Judith Keitel Anja Goettsche Maic Seegel Stefan Leicht Brunhilde Guessregen Sebastian Hickert Philipp Reifenberg Alexandra Cimelli Romane Baranowski Emmanuel Desmartin Elodie Barrau Mark Harrison Tony Bristow Nicholas O'Nei Source Type: research

Cytotoxicity of some choline-based deep eutectic solvents and their effect on solubility of coumarin drug
Eur J Pharm Sci. 2021 Sep 27:106022. doi: 10.1016/j.ejps.2021.106022. Online ahead of print.ABSTRACTThe effect of some deep eutectic solvents (DESs) on the coumarin solubility has been investigated using Hansen solubility parameters (HSP). The solubility of coumarin was measured in aqueous systems containing some DESs based on choline chloride (ChCl) as hydrogen bond acceptor (HBA) with urea (U), ethylene glycol (EG), and glycerol (GLY) as hydrogen bond donors (HBD) by widely applied shake-flask method at T = (298.15 to 313.15) K. The results indicate that coumarin solubility enhances with the concentration of DESs and tem...
Source: European Journal of Pharmaceutical Sciences - September 30, 2021 Category: Drugs & Pharmacology Authors: Mohammad Khorsandi Hemayat Shekaari Masumeh Mokhtarpour Hamed Hamishehkar Source Type: research

Development of Cationic Isometamidium Chloride loaded Long-Acting Lipid Nanoformulation: Optimization, Cellular Uptake, Pharmacokinetics, Biodistribution, and Immunohistochemical Evaluation
Eur J Pharm Sci. 2021 Sep 27:106024. doi: 10.1016/j.ejps.2021.106024. Online ahead of print.ABSTRACTThe aim of the present work involved the development and evaluation of long-acting Isometamidium chloride (ISMM)-docusate sodium (DS) complex loaded lipid nanoparticles (LA ISMM-DS LNP). The development involved screening various anionic complexing agents, including DS, dextran sulphate, and sodium alginate. Anionic DS was selected to synthesize hydrophobic ionic complex (ISMM-DS HIC), which was loaded into lipid nanoparticles (LA ISMM-DS LNP) by in situ complexation followed by the solvent evaporation method. 35-5-folds inc...
Source: European Journal of Pharmaceutical Sciences - September 30, 2021 Category: Drugs & Pharmacology Authors: Dhanashree H Surve Anil B Jindal Source Type: research

Population pharmacokinetic-pharmacodynamic modelling of acetaminophen in preterm neonates with hemodynamically significant patent ductus arteriosus
CONCLUSION: The PK-PD model developed can be used for dosing acetaminophen in premature neonates with hemodynamically significant PDA. Intravenous dose of 20 mg/kg intravenously every six hours is likely to provide a better therapeutic effect than the existing dosing regimen.PMID:34592463 | DOI:10.1016/j.ejps.2021.106023 (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - September 30, 2021 Category: Drugs & Pharmacology Authors: Kannan Sridharan Eman Al Ansari Mwila Mulubwa Arun Prasath Raju Abdulraoof Al Madhoob Muna Al Jufairi Zakariya Hubail Reem Al Marzooq Sadeq Jaafar Radhi Hasan Surulivelrajan Mallaysamy Source Type: research

Cytotoxicity of some choline-based deep eutectic solvents and their effect on solubility of coumarin drug
Eur J Pharm Sci. 2021 Sep 27:106022. doi: 10.1016/j.ejps.2021.106022. Online ahead of print.ABSTRACTThe effect of some deep eutectic solvents (DESs) on the coumarin solubility has been investigated using Hansen solubility parameters (HSP). The solubility of coumarin was measured in aqueous systems containing some DESs based on choline chloride (ChCl) as hydrogen bond acceptor (HBA) with urea (U), ethylene glycol (EG), and glycerol (GLY) as hydrogen bond donors (HBD) by widely applied shake-flask method at T = (298.15 to 313.15) K. The results indicate that coumarin solubility enhances with the concentration of DESs and tem...
Source: European Journal of Pharmaceutical Sciences - September 30, 2021 Category: Drugs & Pharmacology Authors: Mohammad Khorsandi Hemayat Shekaari Masumeh Mokhtarpour Hamed Hamishehkar Source Type: research

Development of Cationic Isometamidium Chloride loaded Long-Acting Lipid Nanoformulation: Optimization, Cellular Uptake, Pharmacokinetics, Biodistribution, and Immunohistochemical Evaluation
Eur J Pharm Sci. 2021 Sep 27:106024. doi: 10.1016/j.ejps.2021.106024. Online ahead of print.ABSTRACTThe aim of the present work involved the development and evaluation of long-acting Isometamidium chloride (ISMM)-docusate sodium (DS) complex loaded lipid nanoparticles (LA ISMM-DS LNP). The development involved screening various anionic complexing agents, including DS, dextran sulphate, and sodium alginate. Anionic DS was selected to synthesize hydrophobic ionic complex (ISMM-DS HIC), which was loaded into lipid nanoparticles (LA ISMM-DS LNP) by in situ complexation followed by the solvent evaporation method. 35-5-folds inc...
Source: European Journal of Pharmaceutical Sciences - September 30, 2021 Category: Drugs & Pharmacology Authors: Dhanashree H Surve Anil B Jindal Source Type: research