scholarly journals Translating the fabrication of protein-loaded poly(lactic-co-glycolic acid) nanoparticles from bench to scale-independent production using microfluidics

2020 ◽  
Vol 10 (3) ◽  
pp. 582-593 ◽  
Author(s):  
Carla B. Roces ◽  
Dennis Christensen ◽  
Yvonne Perrie
Keyword(s):  
Particle Size ◽  
Glycolic Acid ◽  
Polymeric Nanoparticles ◽  
Physicochemical Characteristics ◽  
European Medicines Agency ◽  
Protein Encapsulation ◽  
Human Use ◽  
Rate Ratios ◽  
The Impact ◽  
Process Controls

AbstractIn the formulation of nanoparticles, poly(lactic-co-glycolic acid) (PLGA) is commonly employed due to its Food and Drug Administration and European Medicines Agency approval for human use, its ability to encapsulate a variety of moieties, its biocompatibility and biodegradability and its ability to offer a range of controlled release profiles. Common methods for the production of PLGA particles often adopt harsh solvents, surfactants/stabilisers and in general are multi-step and time-consuming processes. This limits the translation of these drug delivery systems from bench to bedside. To address this, we have applied microfluidic processes to develop a scale-independent platform for the manufacture, purification and monitoring of nanoparticles. Thereby, the influence of various microfluidic parameters on the physicochemical characteristics of the empty and the protein-loaded PLGA particles was evaluated in combination with the copolymer employed (PLGA 85:15, 75:25 or 50:50) and the type of protein loaded. Using this rapid production process, emulsifying/stabilising agents (such as polyvinyl alcohol) are not required. We also incorporate in-line purification systems and at-line particle size monitoring. Our results demonstrate the microfluidic control parameters that can be adopted to control particle size and the impact of PLGA copolymer type on the characteristics of the produced particles. With these nanoparticles, protein encapsulation efficiency varies from 8 to 50% and is controlled by the copolymer of choice and the production parameters employed; higher flow rates, combined with medium flow rate ratios (3:1), should be adopted to promote higher protein loading (% wt/wt). In conclusion, herein, we outline the process controls for the fabrication of PLGA polymeric nanoparticles incorporating proteins in a rapid and scalable manufacturing process.

scholarly journals Formulation and Optimization of Avanafil Biodegradable Polymeric Nanoparticles: A Single-Dose Clinical Pharmacokinetic Evaluation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 596
Author(s):  
Hibah M. Aldawsari ◽  
Usama A. Fahmy ◽  
Fathy Abd-Allah ◽  
Osama A. A. Ahmed
Keyword(s):  
Particle Size ◽  
Polymeric Nanoparticles ◽  
Pde5 Inhibitor ◽  
Area Under The Curve ◽  
Entrapment Efficiency ◽  
Pharmacokinetic Data ◽  
Box Behnken Design ◽  
Fast Absorption ◽  
The Impact ◽  
Phosphodiesterase 5

Avanafil (AVA) is a second-generation phosphodiesterase-5 (PDE5) inhibitor. AVA shows high selectivity to penile tissues and fast absorption, but has a bioavailability of about 36%. The aim was to formulate and optimize AVA-biodegradable nanoparticles (NPs) to enhance AVA bioavailability. To assess the impact of variables, the Box–Behnken design was utilized to investigate and optimize the formulation process variables: the AVA:poly (lactic-co-glycolic acid) (PLGA) ratio (w/w, X1); sonication time (min, X2); and polyvinyl alcohol (PVA) concentration (%, X3). Particle size (nm, Y1) and EE% (%, Y2) were the responses. The optimized NPs were characterized for surface morphology and permeation. Furthermore, a single-oral dose (50 mg AVA) pharmacokinetic investigation on healthy volunteers was carried out. Statistical analysis revealed that all the investigated factors exhibited a significant effect on the particle size. Furthermore, the entrapment efficiency (Y2) was significantly affected by both the AVA:PLGA ratio (X1) and PVA concentration (X3). Pharmacokinetic data showed a significant increase in the area under the curve (1.68 folds) and plasma maximum concentration (1.3-fold) for the AVA NPs when compared with raw AVA. The optimization and formulation of AVA as biodegradable NPs prepared using solvent evaporation (SE) proves a successful way to enhance AVA bioavailability.

scholarly journals FORMULATION AND EVALUATION OF ISORHAMNETIN LOADED POLY LACTIC-CO-GLYCOLIC ACID NANOPARTICLES

2017 ◽  
Vol 10 (11) ◽  
pp. 177
Author(s):  
Kandakumar Settu ◽  
Manju Vaiyapuri
Keyword(s):  
Particle Size ◽  
Glycolic Acid ◽  
Polymeric Nanoparticles ◽  
Double Emulsion ◽  
Spherical Shape ◽  
Particle Size Analysis ◽  
Size Analysis ◽  
Characteristic Variety ◽  
Sem Image ◽  
Flexible Technology

  Objective: The aim of the present study was formulation and evaluation of isorhamnetin loaded poly lactic-co-glycolic acid (PLGA) polymeric nanoparticles (NPs).Methods: The present study was designed to incorporate the isorhamnetin in PLGA formulation by double emulsion solvent evaporation method, which offers a dynamic and flexible technology for enhancing drug solubility due to their biphasic characteristic, variety in design, composition and assembly. Synthesized isorhamnetin-PLGA NPs were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and particle size analyzer. We tested the efficacy of isorhamnetin-PLGA NPs in HepG2 cell lines.Results: From the FTIR result, we concluded that -C-N-, -C=C-, N-H, C-N, N-O, O-H, and C-H are the functional groups present in isorhamnetin-PLGA NPs, SEM image shows spherical shape of particles. The particle size analysis result shows 255-342 nm range of particles. Isorhamnetin-PLGA NPs significantly enhanced (p<0.05) the antiproliferative effect when compared to the plain drug.Conclusion: This study concluded that the newly formulated NP drug delivery systems of isorhamnetin provided an insight into the therapeutic effectiveness of the designed formulation for the treatment of chemotherapy.

scholarly journals Where is Industry Getting it Wrong? A Review of Quality Concerns Raised at Day 120 by the Committee for Medicinal Products for Human Use during European Centralised Marketing Authorisation Submissions for Chemical Entity Medicinal Products

2009 ◽  
Vol 12 (2) ◽  
pp. 181 ◽  
Author(s):  
John Joseph Borg ◽  
Jean-Louis Robert ◽  
George Wade ◽  
George Aislaitner ◽  
Michal Pirozynski ◽  
...  
Keyword(s):  
Marketing Authorisation ◽  
Drug Product ◽  
Point Of View ◽  
Chemical Entity ◽  
European Medicines Agency ◽  
Medicinal Products ◽  
Drug Products ◽  
Human Use ◽  
Consistent Information ◽  
The Impact

ABSTRACT – Purpose. The aim of this study was to identify common trends in the deficiencies identified in the quality part of the dossier during the evaluation of marketing authorisation applications for medicinal products for human use submitted through the EU’s centralised procedure. Methods. We analysed all the adopted Day 120 list of questions on the quality module of 52 marketing authorisation applications for chemical entity medicinal products submitted to the European Medicines Agency and evaluated by the Committee for Medicinal Products for Human Use (CHMP), during 12 consecutive plenary meetings held in 2007 and 2008. Subsequently we calculated the frequency of common deficiencies identified across these applications. Results. Frequencies and trends on quality deficiencies have been recorded and presented for 52 marketing authorisation applications. 32 “Major Objections” originated from 13 marketing authorisation applications. 13 concerned were raised regarding drug substances and 19 for drug products. Furthermore, 905 concerns on drug substance and 1,054 on drug product were also adopted. Conclusions. The impact of the frequencies and trends in quality deficiencies that were identified are discussed from a regulatory point of view. It is expected that the results of this study will not only be of interest to pharmaceutical companies but will also aid regulators’ in obtaining consistent information on drug products based on transparent rules safeguarding the necessary pharmaceutical quality of medicinal products.

scholarly journals POLYMERIC NANOPARTICLES FOR IMPROVED BIOAVAILABILITY OF CILNIDIPINE

2017 ◽  
Vol 9 (4) ◽  
pp. 129 ◽  
Author(s):  
Rohit Mishra ◽  
Showkat R. Mir ◽  
Saima Amin
Keyword(s):  
Particle Size ◽  
Glycolic Acid ◽  
Antihypertensive Effect ◽  
Polymeric Nanoparticles ◽  
Relative Bioavailability ◽  
Diffusion Method ◽  
The Novel ◽  
Hypertensive Rats ◽  
Treatment Of Hypertension ◽  
Emulsification Solvent Evaporation

Objective: In the present study, we aimed to optimize, characterize and evaluate poly lactic-glycolic acid nanoparticles of cilnidipine for improved permeation across the gastrointestinal tract.Methods: Poly lactic-glycolic acid-cilnidipine (PLGA-CIL) nanoparticles were prepared by an emulsification solvent evaporation/diffusion method using polyvinyl alcohol (PVA) as a surfactant. The prepared nanoparticles were successfully characterized for particle size, shape, drug release and pharmacological effect.Results: Polymeric nanoparticles of cilnidipine at a dose of 10 mg had a small particle size of 272 nm with smooth morphology. Nearly 81% of the drug was encapsulated in the polymeric structure and showed 18.99±0.59% of release at pH 1.2 within 3h, however, at pH 6.8 the release was 80.89±1.59%. The formulation had a better antihypertensive effect on methylprednisolone-induced hypertensive rats. The relative bioavailability of the nanoparticles was found to be 2.44 and 2.94 fold higher than the tablet and drug suspension respectively.Conclusion: The results demonstrated that the novel delivery system offers an effective strategy for treatment of hypertension.

scholarly journals Timeline of Authorization and Reimbursement for Oncology Drugs in Italy in the Last 3 Years

2017 ◽  
Vol 1 ◽  
pp. maapoc.0000007 ◽  
Author(s):  
Mariangela Prada ◽  
Matteo Ruggeri ◽  
Carmen Sansone ◽  
Dalila De Fazio ◽  
Alessia Tettamanti ◽  
...  
Keyword(s):  
European Medicines Agency ◽  
Approval Time ◽  
Evaluation Time ◽  
Italian Market ◽  
Health Care Structure ◽  
Care Structure ◽  
The Mean ◽  
Human Use ◽  
The Impact ◽  
Mean Time

Introduction The main purpose of this analysis was to quantify the time elapsed between the validation date of European Medicines Agency (EMA) centralized procedure and the first purchase of a product by at least 1 Italian health care structure, evaluating different variables that affect the process, the number of products approved by the Committee for Medicinal Products for Human Use (CHMP) that are available on the Italian market (July 2016), and the impact of the Cnn class for oncology drugs in Italy. Methods A panel of oncology products has been defined, which considered drugs approved by the EMA between January 2013 and December 2015, and authorized for the treatment of oncology diseases, excluding generics. Data were obtained via the EMA website by the Agenzia Italiana del Farmaco (AIFA; the Italian Medicine Agency) meeting reports, by official administrative acts of marketing authorization, and the date of the first purchase (first day of the first handling month). Results The mean time of EMA evaluation for the considered panel of medicines was about 441 days (standard deviation (SD) 108; range 266-770); the average approval time for AIFA was about 248 days (SD 131; range 85-688). Interestingly, the mean AIFA evaluation time decreased significantly from 264 days for products submitted to AIFA assessment in 2013-2014 to 219 days for products evaluated in 2015-2016. Focusing on the regional access, both the timing and the number of drugs available for patients were widely different from region to region. Discussion A reduction in the approval time in the last 2 years has been observed in Italy. However, several variables influence the efficiency of the process and need to be addressed to make the access to drugs timely and efficient.

scholarly journals Applying Box–Behnken Design for Formulation and Optimization of PLGA-Coffee Nanoparticles and Detecting Enhanced Antioxidant and Anticancer Activities

Polymers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 144
Author(s):  
Nouran S. Sharaf ◽  
Amro Shetta ◽  
Jailan E. Elhalawani ◽  
Wael Mamdouh
Keyword(s):  
Particle Size ◽  
In Vitro Release ◽  
Physicochemical Characteristics ◽  
Plga Nanoparticles ◽  
Anticancer Activities ◽  
Particle Size Reduction ◽  
Box Behnken Design ◽  
Surface Stability ◽  
The Impact

In an attempt to prove biological activity enhancement upon particle size reduction to the nanoscale, coffee (Cf) was chosen to be formulated into poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) using the single emulsion-solvent evaporation (SE-SE) method via Box–Behnken Design (BBD) to study the impact of certain process and formulation parameters on the particle size and size homogeneity, surface stability and encapsulation efficiency (EE%). The coffee-loaded PLGA (PLGA-Cf) NPs were characterized by different methods to aid in selecting the optimum formulation conditions. The desirable physicochemical characteristics involved small particle sizes with an average of 318.60 ± 5.65 nm, uniformly distributed within a narrow range (PDI of 0.074 ± 0.015), with considerable stability (Zeta Potential of −20.50 ± 0.52 mV) and the highest EE% (85.92 ± 4.01%). The antioxidant and anticancer activities of plain PLGA NPs, pure Cf and the optimum PLGA-Cf NPs, were evaluated using 2,2-Diphenyl-1-picryl-hydrazyl (DPPH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. As a result of nano-encapsulation, antioxidant activity was enhanced by 26.5%. Encapsulated Cf showed higher anticancer potency than pure Cf against different cancerous cell lines with an increase of 86.78%, 78.17%, 85.84% and 84.84% against MCF-7, A-549, HeLa and HepG-2, respectively. The in vitro release followed the Weibull release model with slow and biphasic release profile in both tested pH media, 7.4 and 5.5.

Novel Applications of Nanotechnology in Controlling HIV and HSV Infections

2020 ◽  
Vol 12 ◽  
Author(s):  
Sai Akilesh M ◽  
Ashish Wadhwani
Keyword(s):  
Drug Delivery ◽  
Viral Infections ◽  
Polymeric Nanoparticles ◽  
Volume Ratio ◽  
Fold Increase ◽  
Multi Drug Resistance ◽  
Health Crisis ◽  
Pharmaceutical Properties ◽  
Simplex Virus ◽  
The Impact

: Infectious diseases have been prevalent since many decades and viral pathogens have caused global health crisis and economic meltdown on a devastating scale. High occurrence of newer viral infections in the recent years, in spite of the progress achieved in the field of pharmaceutical sciences defines the critical need for newer and more effective antiviral therapies and diagnostics. The incidence of multi-drug resistance and adverse effects due to the prolonged use of anti-viral therapy is also a major concern. Nanotechnology offers a cutting edge platform for the development of novel compounds and formulations for biomedical applications. The unique properties of nano-based materials can be attributed to the multi-fold increase in the surface to volume ratio at the nano-scale, tunable surface properties of charge and chemical moieties. Idealistic pharmaceutical properties such as increased bioavailability and retention times, lower toxicity profiles, sustained release formulations, lower dosage forms and most importantly, targeted drug delivery can be achieved through the approach of nanotechnology. The extensively researched nano-based materials are metal and polymeric nanoparticles, dendrimers and micelles, nano-drug delivery vesicles, liposomes and lipid based nanoparticles. In this review article, the impact of nanotechnology on the treatment of Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus (HSV) viral infections during the last decade are outlined.

scholarly journals Waterfall Algorithm as a tool of investigation the geometrical features of granular porous media

2021 ◽  
Author(s):  
Wojciech Sobieski
Keyword(s):  
Particle Size ◽  
Porous Media ◽  
Lattice Boltzmann ◽  
Granular Media ◽  
Density Ratio ◽  
Geometrical Features ◽  
Granular Porous Media ◽  
Collision Density ◽  
Boltzmann Method ◽  
The Impact

AbstractThe paper describes the so-called Waterfall Algorithm, which may be used to calculate a set of parameters characterising the spatial structure of granular porous media, such as shift ratio, collision density ratio, consolidation ratio, path length and minimum tortuosity. The study is performed for 1800 different two-dimensional random pore structures. In each geometry, 100 individual paths are calculated. The impact of porosity and the particle size on the above-mentioned parameters is investigated. It was stated in the paper, that the minimum tortuosity calculated by the Waterfall Algorithm cannot be used directly as a representative tortuosity of pore channels in the Kozeny or the Carman meaning. However, it may be used indirect by making the assumption that a unambiguous relationship between the representative tortuosity and the minimum tortuosity exists. It was also stated, that the new parameters defined in the present study are sensitive on the porosity and the particle size and may be therefore applied as indicators of the geometry structure of granular media. The Waterfall Algorithm is compared with other methods of determining the tortuosity: A-Star Algorithm, Path Searching Algorithm, Random Walk technique, Path Tracking Method and the methodology of calculating the hydraulic tortuosity based on the Lattice Boltzmann Method. A very short calculation time is the main advantage of the Waterfall Algorithm, what meant, that it may be applied in a very large granular porous media.

PP469 From Theory To Practice: Which Value Framework Is Applied For Onco-Hematology Therapies In Italy? A 5-year Retrospective Analysis

2020 ◽  
Vol 36 (S1) ◽  
pp. 37-37
Author(s):  
Americo Cicchetti ◽  
Rossella Di Bidino ◽  
Entela Xoxi ◽  
Irene Luccarini ◽  
Alessia Brigido
Keyword(s):  
Real World ◽  
Ad Hoc ◽  
Grey Literature ◽  
National Level ◽  
Pharmaceutical Products ◽  
European Medicines Agency ◽  
The Real ◽  
R Process ◽  
The One ◽  
The Impact

IntroductionDifferent value frameworks (VFs) have been proposed in order to translate available evidence on risk-benefit profiles of new treatments into Pricing & Reimbursement (P&R) decisions. However limited evidence is available on the impact of their implementation. It's relevant to distinguish among VFs proposed by scientific societies and providers, which usually are applicable to all treatments, and VFs elaborated by regulatory agencies and health technology assessment (HTA), which focused on specific therapeutic areas. Such heterogeneity in VFs has significant implications in terms of value dimension considered and criteria adopted to define or support a price decision.MethodsA literature research was conducted to identify already proposed or adopted VF for onco-hematology treatments. Both scientific and grey literature were investigated. Then, an ad hoc data collection was conducted for multiple myeloma; breast, prostate and urothelial cancer; and Non Small Cell Lung Cancer (NSCLC) therapies. Pharmaceutical products authorized by European Medicines Agency from January 2014 till December 2019 were identified. Primary sources of data were European Public Assessment Reports and P&R decision taken by the Italian Medicines Agency (AIFA) till September 2019.ResultsThe analysis allowed to define a taxonomy to distinguish categories of VF relevant to onco-hematological treatments. We identified the “real-world” VF that emerged given past P&R decisions taken at the Italian level. Data was collected both for clinical and economical outcomes/indicators, as well as decisions taken on innovativeness of therapies. Relevant differences emerge between the real world value framework and the one that should be applied given the normative framework of the Italian Health System.ConclusionsThe value framework that emerged from the analysis addressed issues of specific aspects of onco-hematological treatments which emerged during an ad hoc analysis conducted on treatment authorized in the last 5 years. The perspective adopted to elaborate the VF was the one of an HTA agency responsible for P&R decisions at a national level. Furthermore, comparing a real-world value framework with the one based on the general criteria defined by the national legislation, our analysis allowed identification of the most critical point of the current national P&R process in terms ofsustainability of current and future therapies as advance therapies and agnostic-tumor therapies.

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