Influence of Concentration on Release and Permeation Process of Model Peptide Substance-Corticotropin-From Semisolid Formulations

The transdermal route of administration of drug substances allows clinicians to obtain a therapeutic effect bypassing the gastrointestinal tract, where the active substance could be inactivated. The hormonal substance used in the study-corticotropin (ACTH)-shows systemic effects. Therefore, the study of the effect of the type of ointment base and drug concentration on the release rate and also permeation rate in in vivo simulated conditions may be a valuable source of information for clinical trials to effectively optimize corticotropin treatment. This goal was achieved by preparation ointment formulation selecting the appropriate ointment base and determining the effect of ACTH concentration on the release and permeation studies of the ACTH. Semi-solid preparations containing ACTH were prepared using Unguator CITO e/s. The release study of ACTH was tested using a modified USP apparatus 2 with Enhancer cells. The permeation study was conducted with vertical Franz cells. Rheograms of hydrogels were made with the use of a universal rotational rheometer. The dependence of the amount of released and permeated hormone on the ointment concentration was found. Based on the test of ACTH release from semi-solid formulations and evaluation of rheological parameters, it was found that glycerol ointment is the most favourable base for ACTH. The ACTH release and permeation process depends on both viscosity and ACTH concentration. The higher the hormone concentration, the higher the amount of released ACTH but it reduces the amount of ACTH penetrating through porcine skin.

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In Silico Assessment of ADME Properties: Advances in Caco-2 Cell Monolayer Permeability Modeling

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666181130140350 ◽

2019 ◽

Vol 18 (26) ◽

pp. 2209-2229 ◽

Cited By ~ 4

Author(s):

Hai Pham-The ◽

Miguel Á. Cabrera-Pérez ◽

Nguyen-Hai Nam ◽

Juan A. Castillo-Garit ◽

Bakhtiyor Rasulev ◽

...

Keyword(s):

Intestinal Absorption ◽

In Silico ◽

Review Paper ◽

Cell Monolayer ◽

Cell Permeability ◽

Drug Substances ◽

Wide Range ◽

Modeling Techniques

One of the main goals of in silico Caco-2 cell permeability models is to identify those drug substances with high intestinal absorption in human (HIA). For more than a decade, several in silico Caco-2 models have been made, applying a wide range of modeling techniques; nevertheless, their capacity for intestinal absorption extrapolation is still doubtful. There are three main problems related to the modest capacity of obtained models, including the existence of inter- and/or intra-laboratory variability of recollected data, the influence of the metabolism mechanism, and the inconsistent in vitro-in vivo correlation (IVIVC) of Caco-2 cell permeability. This review paper intends to sum up the recent advances and limitations of current modeling approaches, and revealed some possible solutions to improve the applicability of in silico Caco-2 permeability models for absorption property profiling, taking into account the above-mentioned issues.

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Development, Pre-clinical Investigation and Histopathological Evaluation of Metronidazole Loaded Topical Formulation for Treatment of Skin Inflammatory disorders

Drug Delivery Letters ◽

10.2174/2210303110999200821123047 ◽

2020 ◽

Vol 10 ◽

Author(s):

Divya Thakur ◽

Gurpreet Kaur ◽

Sheetu Wadhwa ◽

Ashana Puri

Keyword(s):

Ex Vivo ◽

Clinical Investigation ◽

In Vivo Studies ◽

Tween 20 ◽

Inflammatory Disorders ◽

Rat Paw Edema ◽

Ex Vivo Permeation ◽

Permeation Studies ◽

Anti Inflammatory

Background: Metronidazole (MTZ) is an anti-oxidant and anti-inflammatory agent with beneficial therapeutic properties. The hydrophilic nature of molecule limits its penetration across the skin. Existing commercial formulations have limitations of inadequate drug concentration present at target site, which requires frequent administration and poor patient compliance. Objective: The aim of current study was to develop and evaluate water in oil microemulsion of Metronidazole with higher skin retention for treatment of inflammatory skin disorders. Methods: Pseudo ternary phase diagrams were used in order to select the appropriate ratio of surfactant and co-surfactant and identify the microemulsion area. The selected formulation consisted of Capmul MCM as oil, Tween 20 and Span 20 as surfactant and co-surfactant, respectively, and water. The formulation was characterized and evaluated for stability, Ex vivo permeation studies and in vivo anti-inflammatory effect (carrageenan induced rat paw edema, air pouch model), anti-psoriatic activity (mouse-tail test). Results: The particle size analyses revealed average diameter and polydispersity index of selected formulation to be 16 nm and 0.373, respectively. The results of ex vivo permeation studies showed statistically higher mean cumulative amount of MTZ retained in rat skin from microemulsion i.e. 21.90 ± 1.92 μg/cm2 which was 6.65 times higher as compared to Marketed gel (Metrogyl gel®) with 3.29 ± 0.11 μg/cm2 (p<0.05). The results of in vivo studies suggested the microemulsion based formulation of MTZ to be similar in efficacy to Metrogyl gel®. Conclusion: Research suggests efficacy of the developed MTZ loaded microemulsion in treatment of chronic skin inflammatory disorders.

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Formulation and in vitro evaluation of self-nanoemulsifying liquisolid tablets of furosemide

Scientific Reports ◽

10.1038/s41598-020-79940-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lena Dalal ◽

Abdul Wahab Allaf ◽

Hind El-Zein

Keyword(s):

Theoretical Model ◽

Castor Oil ◽

In Vivo Studies ◽

Coating Materials ◽

Peg 400 ◽

The Mean ◽

Usp Apparatus ◽

Solid System

AbstractSelf-nanoemulsifying drug delivery systems (SNEDDS) were used to enhance the dissolution rate of furosemide as a model for class IV drugs and the system was solidified into liquisolid tablets. SNEDDS of furosemide contained 10% Castor oil, 60% Cremophor EL, and 30% PEG 400. The mean droplets size was 17.9 ± 4.5 nm. The theoretical model was used to calculate the amounts of the carrier (Avicel PH101) and coating materials (Aerosil 200) to prepare liquisolid powder. Carrier/coating materials ratio of 5/1 was used and Ludipress was added to the solid system, thus tablets with hardness of 45 ± 2 N were obtained. Liquisolid tablets showed 2-folds increase in drug release as compared to the generic tablets after 60 min in HCl 0.1 N using USP apparatus-II. Furosemide loaded SNEDDS tablets have great prospects for further in vivo studies, and the theoretical model is useful for calculating the adequate amounts of adsorbents required to solidify these systems.

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Predictivity of standardized and controlled permeation studies: Ex vivo – In vitro – In vivo correlation for sublingual absorption of propranolol

European Journal of Pharmaceutics and Biopharmaceutics ◽

10.1016/j.ejpb.2021.09.002 ◽

2021 ◽

Vol 169 ◽

pp. 12-19

Author(s):

Haidara Majid ◽

Anke Bartel ◽

Bjoern B. Burckhardt

Keyword(s):

Ex Vivo ◽

Permeation Studies

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Transcriptome Profiling of Panc-1 Spheroid Cells with Pancreatic Cancer Stem Cells Properties Cultured by a Novel 3D Semi-Solid System

Cellular Physiology and Biochemistry ◽

10.1159/000491479 ◽

2018 ◽

Vol 47 (5) ◽

pp. 2109-2125 ◽

Cited By ~ 6

Author(s):

Zhaocong Yang ◽

Yanfeng Zhang ◽

Tingting Tang ◽

Qinhua Zhu ◽

Wanyue Shi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Culture System ◽

High Throughput Sequencing ◽

Semi Solid ◽

Pancreatic Cancer Stem Cells ◽

Solid System

Background/Aims: Pancreatic cancer remains one of the deadliest human malignancies, the lethality of which may be attributed to the presence of pancreatic cancer stem cells (PCSCs), a small subpopulation of cells existing within pancreatic tumor with high carcinogenesis. Therefore, it is crucial to establish an efficient enrichment and culture system of PCSCs and identify the key genes involved in the regulation of PCSCs. The three-dimensional (3D) liquid suspension mammosphere culture system has been established for enrichment and culture of PCSCs in vitro as the cell spheres are likely to originate from individual cell clone, but it has been challenged because the cell spheroids could be a result of cell aggregation. Methods: We optimized the existing culture system by adding methylcellulose to create a 3D semi-solid system which prevented the non-specific aggregation. Then we identified the CSC properties of Panc-1 spheroid cells cultured by this system by detecting the genes associated with stemness and by evaluation of the tumorigenicity in vitro and in vivo through invasion, migration and xenograft experiments methods. Subsequently, we performed high-throughput sequencing (HTS) of the Panc-1 spheroid cells. Results: We confirmed the PCSCs properties and high malignancy of the Panc-1 spheroid cells enriched by our novel 3D semi-solid system both in vitro and in vivo. Hundreds of mRNA, microRNA (miRNA) and dozens of long non-coding RNA (LncRNA) were identified to be differentially regulated in PCSCs-like Panc-1 spheroid cells compared with their parental cells by HTS. Conclusions: Our results demonstrate an efficient enrichment and culture system for Panc-1 spheroid cells with the PCSCs properties. The differentially expressed genes and their targets identified by the HTS of the Panc-1 spheroid cells can serve as new potential biomarkers for pancreatic cancer diagnosis and targeted therapy.

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5-Fluorouracil-Loaded Transfersome as Theranostics in Dermal Tumor of Hypertrophic Scar Tissue

Journal of Nanomaterials ◽

10.1155/2015/253712 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Z. Zhang ◽

X. Wang ◽

X. Chen ◽

Y. Wo ◽

Y. Zhang ◽

...

Keyword(s):

High Performance ◽

Scar Tissue ◽

Hypertrophic Scars ◽

Transdermal Drug Delivery System ◽

Permeation Studies ◽

Fluorescent Agent ◽

Hypertrophic Scar Tissue ◽

Laser Confocal Microscope

To investigate the ability of transfersomal gel carrying the antiscarring agent (5-FU) to permeate hypertrophic scarsin vivoandin vitro, scar permeation studies were performed after the agent was labeled with the fluorescent agent, rhodamine 6GO. Laser confocal microscope was employed to dynamically observe the effects of transfersomal gel carrying 5-FU at different time points. High-performance liquid chromatography (HPLC) was used to analyze the contents of the agent in the scar tissues at different hours after administration. Scar elevation index (SEI) was used to evaluate the changes of the ear scar models in rabbits. Compared with the PBS gel of 5-FU, the transfersomal gel displayed greater permeation rate and depth, as well as a higher content retention of the agent in scar tissues. Local administrations of the agent for some certain periods effectively inhibited the hyperplasia of ear scars in rabbits. Transfersomes can be chosen as a potential transdermal drug delivery system.

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Improved micropropagation and foliar micromorphological studies in Turnera ulmifolia L. – An important medicinal plant

Folia Horticulturae ◽

10.2478/fhort-2018-0024 ◽

2018 ◽

Vol 30 (2) ◽

pp. 283-294 ◽

Cited By ~ 1

Author(s):

Mani Manokari ◽

Mahipal S. Shekhawat

Keyword(s):

Shoot Proliferation ◽

Nodal Segments ◽

Naphthalene Acetic Acid ◽

Ms Medium ◽

Half Strength ◽

Turnera Ulmifolia ◽

Semi Solid ◽

Number Of Shoots

Abstract The present study reports an efficient in vitro propagation system for Turnera ulmifolia using nodal segments as explants. Turnera ulmifolia (Passifloraceae) is an important garden plant with multipotent medicinal values. Effective shoot proliferation was achieved on agar gelled MS medium (Murashige and Skoog, 1962). The maximum number of shoots (8.3 ± 0.57) per initial explant was obtained on MS medium supplemented with 8.88 mM of 6-benzylaminopurine (BAP) and 0.54 mM of α-naphthalene acetic acid (NAA). The highest number of shoots (59.5 ± 2.10) proliferated on semi-solid MS medium (with agar) augmented with 2.22 mM of BAP and 2.32 mM of kinetin (Kin) along with 0.54 mM of NAA. Longer (4-5 cm) and healthy shoots were rooted (12.0 ± 0.10 roots per shoot) on half-strength MS medium fortified with 9.84 mM of indole-3 butyric acid (IBA). The in vitro regenerated plantlets were hardened in the greenhouse and transferred to the field. Significant developmental changes were observed in the foliar micromorphology of in vitro raised plantlets when these were transferred to the field. The stomatal index was gradually reduced (26.72 to 21.25) in the leaves from in vitro to field environments. But, vein-islets and veinlet terminations (13.4 and 7.6) were increased (39.7 and 18.4) respectively from in vitro to in vivo grown plants. Simple, unicellular, less frequent and underdeveloped trichomes were observed with the leaves of in vitro plants but fully developed trichomes recorded in the field transferred plants. The study could help in understanding the response and adaptation of tissue culture raised plantlets towards changed environmental conditions.

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