How Well Do In Vitro Particle Size Measurements Predict Drug Delivery In Vivo?

1998 ◽  
Vol 11 (s1) ◽  
pp. S-97-S-104 ◽  
Author(s):  
STEPHEN P. NEWMAN
Keyword(s):  
Drug Delivery ◽  
Particle Size

scholarly journals Development, Optimisation and Evaluation of Ketoprofen Lipospheres

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1853-1863
Author(s):  
Shubhra Rai ◽  
Gopal Rai ◽  
Ashish Budhrani
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Research Work ◽  
Extended Period ◽  
Entrapment Efficiency ◽  
Inflammatory Activity ◽  
Scanning Calorimetry ◽  
Anti Inflammatory

Lipospheres represent a novel type of fat-based encapsulation system produced for the topical drug delivery of bioactive compounds. The goal of this research work was to develop lipospheres, including ketoprofen applied for topical skin drug delivery. Ketoprofen lipospheres were formulated by melt emulsification method using stearic acid and Phospholipon® 90G. The lipospheres were analysed in terms of particle size and morphology, entrapment efficiency, Differential scanning calorimetry, In-vitro drug release, In-vivo (Anti-inflammatory activity). Outcomes of research revealed that particle size was found to be 9.66 µm and entrapment efficiency 86.21 ± 5.79 %. In-vivo, the study of ketoprofen loaded lipospheres formulation shows a higher plain formulation concentration in plasma (5.61 mg/mL). For dermis, ketoprofen retention was 27.02 ± 5.4 mg/mL for the lipospheres formulation, in contrast to that of the plain formulation group (10.05 ± 2.8 mg/mL). The anti-inflammatory effect of liposphere drug delivery systems was assessed by the xylene induced ear oedema technique and compared with marketed products. Finally, it seems that the liposphere drug delivery system possesses superior anti-inflammatory activity as compared to the marketed product gel consistencies. Liposphere may be capable of entrapping the medicament at very high levels and controlling its release over an extended period. Liposphere furnishes a proper size for topical delivery as well as is based on non-irritating and non-toxic lipids; it’s a better option for application on damaged or inflamed skin.

Formulation and evaluation of resveratrol loaded cubosomal nanoformulation for topical delivery

2020 ◽  
Vol 17 ◽  
Author(s):  
Bhaskar Kurangi ◽  
Sunil Jalalpure ◽  
Satveer Jagwani
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
Topical Application ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Drug Permeation

Aim: The aim of the study was to formulate, characterize, and evaluate the resveratrol-loaded cubosomes (RC) through topical application. Background: Resveratrol (RV) is a nutraceutical compound that has exciting pharmacological potential in different diseases including cancers. Many studies of resveratrol have been reported for anti-melanoma activity. Due to its low bioavailability, the activities of resveratrol are strongly limited. Hence, an approach with nanotechnology has been done to increase its activity through transdermal drug delivery. Objective: To formulate, characterize, and evaluate the resveratrol-loaded cubosomes (RC). To evaluate resveratrol-loaded cubosomal gel (RC-Gel) for its topical application. Methods: RC was formulated by homogenization technique and optimized using a 2-factor 3-level factorial design. Formulated RCs were characterized for particle size, zeta potential, and entrapment efficiency. Optimized RC was evaluated for in vitro release and stability study. Optimized RC was further formulated into cubosomal gel (RC-Gel) using carbopol and evaluated for drug permeation and deposition. Furthermore, developed RC-Gel was evaluated for its topical application using skin irritancy, toxicity, and in vivo local bioavailability studies. Results: The optimized RC indicated cubic-shaped structure with mean particle size, entrapment efficiency, and zeta potential were 113±2.36 nm, 85.07 ± 0.91%, and -27.40 ± 1.40 mV respectively. In vitro drug release of optimized RC demonstrated biphasic drug release with the diffusion-controlled release of resveratrol (RV) (87.20 ± 2.25%). The RC-Gel demonstrated better drug permeation and deposition in mice skin layers. The composition of RC-Gel has been proved non-irritant to the mice skin. In vivo local bioavailability study depicted the good potential of RC-Gel for skin localization. Conclusion: The RC nanoformulation proposes a promising drug delivery system for melanoma treatment simply through topical application.

Casuarina equisetifoliaExtract Loaded Phytosomes: Optimization, Characterization andIn vivoEvaluation of Antidiabetic and Antihyperlipidemic Activities in Wistar Rats

2019 ◽  
Vol 9 (2) ◽  
pp. 116-133 ◽  
Author(s):  
Anjana Rani ◽  
Sunil Kumar ◽  
Roop K. Khar
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Therapeutic Efficacy ◽  
Entrapment Efficiency ◽  
Herbal Extract ◽  
Casuarina Equisetifolia ◽  
Novel Drug

Background:Herbal extracts have brilliant in-vitro activity but less in-vivo action in light of their macromolecular size and poor lipid solubility bringing about poor absorption and low bioavailability. These issues can be corrected by designing novel drug delivery systems. Phytosomes provide better absorption and bioavailability when compared to conventional herbal extract.Objective:This paper deals with the preparation, optimization and characterization of Phytosome of plant extract and in vivo assessment of antidiabetic and antihyperlipidemic activity for improved therapeutic efficacy having sufficient stability.Methods:Preliminary distinctive strategies were utilized to get ready Phytosome and antisolvent precipitation method was chosen. The formulation was guided by a full factorial design to study the effect of Independent variable on various dependent variables and resulted in an optimised product. Response contour plots were generated for each response factor to predict a phytosomal composition that yields phytosome formulation having least particle size and maximum entrapment efficiency.Results:Mean particle size, entrapment efficiency and Span value were found to be 295 ± 0.53nm, 82.43 ± 1.65% and 0.34 ± 0.14 respectively. Zeta potential was found to be 19.35mv, indicating the formation of stable formulation. In vitro release study described that the drug release follows the Korsmeyer- Peppas kinetic model. The results proved that Phytosomes of Casuarina equisetifolia extract exhibited more antidiabetic potential and antihyperlipidemic properties as compared to crude Casuarina extract.Conclusion:Phytosomes of Casuarina equestifolia extract was successfully formulated having good entrapment efficiency and physico-chemical characterization of the optimized product, confirming the formation of stable formulation. In vivo antidiabetic activity confirmed better potential of the optimised formulation. Consequently, it has been presumed that Phytosomes of Casuarina equisetifolia extract serve as a useful novel drug delivery system and provide more therapeutic efficacy than conventional plant extracts.

scholarly journals Folate Receptor-Targeted Albumin Nanoparticles Based on Microfluidic Technology to Deliver Cabazitaxel

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1571 ◽  
Author(s):  
Fanchao Meng ◽  
Yating Sun ◽  
Robert J. Lee ◽  
Guiyuan Wang ◽  
Xiaolong Zheng ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Particle Size Distribution ◽  
Size Distribution ◽  
Morphological Observation ◽  
Mixing Efficiency ◽  
Microfluidic Technology ◽  
Delivery Efficiency

Microfluidic technology (MF) has improved the formulation of nanoparticles (NPs) by achieving uniform particle size distribution, controllable particle size, and consistency. Moreover, because liquid mixing can be precisely controlled in the pores of the microfluidic chip, maintaining high mixing efficiency, MF exerts higher of NP encapsulation efficiency (EE) than conventional methods. MF-NPs-cabazitaxel (CTX) particles (MF-NPs-CTX) were first prepared by encapsulating CTX according to MF. Folate (FA)- Polyethylene glycol (PEG)-NPs-CTX particles (FA-PEG-NPs-CTX) were formulated by connecting FA to MF-NPs-CTX to endow NPs with targeted delivery capability. Accordingly, the mean particle size of FA-PEG-NPs-CTX increased by approximately 25 nm, as compared with MF-NPs-CTX. Upon morphological observation of FA-PEG-NPs-CTX and MF-NPs-CTX by transmission electron microscopy (TEM), all NPs were spherical and particle size distribution was uniform. Moreover, the increased delivery efficiency of CTX in vitro and its strong tumor inhibition in vivo indicated that FA-PEG-NPs-CTX had a powerful tumor-suppressive effect both in vitro and in vivo. In vivo imaging and pharmacokinetic data confirmed that FA-PEG-NPs-CTX had good drug delivery efficiency. Taken together, FA-PEG-NPs-CTX particles prepared using MF showed high efficient and targeted drug delivery and may have a considerable driving effect on the clinical application of targeting albumin NPs.

scholarly journals Design and in vivo Evaluation of Manidipine by Self-Nanoemulsifying Drug Delivery Systems

2019 ◽  
Vol 11 (06) ◽  
Author(s):  
S Srikanth Reddy ◽  
G Suresh
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Drug Release ◽  
Spherical Shape ◽  
Pharmacokinetic Studies ◽  
In Vivo Evaluation ◽  
Enhanced Solubility ◽  
Pure Drug

The current research is aimed at developing liquid self-nanoemulsifying drug delivery system (liquid-SNEDDS) of Manidipine for enhanced solubility and oral bioavailability. The Manidipine SNEDDS are formulated with excipients comprising of Capmul MCM (oil phase), Transcutol P (surfactant) Lutrol L 300 as co-surfactant. The prepared fifteen formulations of Manidipine SNEDDS analysed for emulsification time, percentage transmittance, particle size, in vitro drug release, and stability studies. In vivo pharmacokinetic studies of the optimized formulation were carried out in Wistar rats in comparison with control (pure drug). The morphology of Manidipine SNEDDS indicates spherical shape with uniform particle distribution. The percentage drug release from optimized formulation F14 is 98.24 ± 5.14%. The particle size F14 formulation was 22.4 nm and Z-Average 23.3 nm. The PDI and zeta potential of Manidipine SNEDDS optimized formulation (F14) were 0.313 and-5.1mV respectively. From in vivo bioavailability data the optimized formulation exhibited a significantly greater Cmax and Tmax of the SNEDDS was found to be 3.42 ± 0.46ng/ml and 2.00 ± 0.05 h respectively. AUC0-∞ infinity for formulation was significantly higher (11.25 ± 3.45 ng.h/ml) than pure drug (7.45 ± 2.24ng. h/ml). Hence a potential SNEDDS formulation of Manidipine developed with enhanced solubility and bioavailability.

scholarly journals FORMULATION AND IN VIVO EVALUATION OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM OF RAMIPRIL IN WISTAR RATS

2021 ◽  
pp. 126-136
Author(s):  
NALLAPU JAYAPAL ◽  
YAMSANI VAMSHI VISHNU
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Drug Release ◽  
Systemic Absorption ◽  
Content Uniformity ◽  
Stability Studies ◽  
In Vitro Drug Release ◽  
Pure Drug

Objective: The aim was to formulate and evaluate self-nanoemulsifying drug delivery systems (SNEDDS) of ramipril, an antihypertensive drug to improve the solubility and bioavailability. Methods: Based on solubility studies oil phase (Sefsol 218), surfactant (Acrysol EL135), and cosurfactant (Transcutol P), respectively, were selected to prepare SNEDDS. Ramipril SNEDDS optimized employing box-Behnken design through the study of factors. All formulations were evaluated for particle size, zeta potential (ZP), polydispersity index (PDI), entrapment efficiency (EE), drug content, and in vitro drug release. The optimized formulation was characterized for Fourier transform infrared (FTIR), scanning electron microscopy (SEM), stability studies, and pharmacokinetic study. Results: The mean particle size, PDI, ZP, EE, content uniformity, and in vitro drug release profile of optimized ramipril-loaded SNEDDS (RF14) were found to be 75.3±2.21nm, 0.126±0.05, −24.4±5.78mV, 98.74±1.97%, 99.52±1.67%, and 98.65±1.73%, respectively. FTIR studies revealed that there is no incompatibility between drug and excipients, SEM images exhibited nanoparticles to be more porous and in spherical shape. Stability studies indicated formulation was stable for 6 months. In vivo studies were conducted for optimized formulation RF14, the Tmax was found to be 0.5±0.62 and 0.5±0.95 h for the optimized and commercial formulations respectively, while Cmax was 25.16±1.73 ng/mL was significant (p<0.05) as compared to the ramipril pure drug 8.02±0.086 ng/mL. AUC0-t of the SNEDDS formulation was higher 355.49±1.76ng h/ml compared to pure drug 116.57±1.64 ng h/ml indicated higher amount of drug concentration in blood proving better systemic absorption of ramipril from SNEDDS formulation as compared to the pure drug. Conclusion: It is concluded from the results that ramipril was successfully formulated into SNEDDS with higher concentration with fast action.

Indinavir-Loaded Nanostructured Lipid Carriers to Brain Drug Delivery: Optimization, Characterization and Neuropharmacokinetic Evaluation

2019 ◽  
Vol 16 (4) ◽  
pp. 341-354 ◽  
Author(s):  
Mohammad Nasiri ◽  
Amir Azadi ◽  
Mohammad Reza Saghatchi Zanjani ◽  
Mehrdad Hamidi
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Zeta Potential ◽  
Average Particle Size ◽  
In Vitro Release ◽  
Free Drug ◽  
Average Particle ◽  
The Brain

Purpose: As an anti-retroviral Protease Inhibitor (PI), Indinavir (IDV) is part of the regimen known as Highly Active Anti-Retroviral Therapy (HAART) widely used for Human Immunodeficiency Virus (HIV) infection. The drug efficiency in treatment of the brain manifestations of HIV is, however, limited which is mainly due to the efflux by P-glycoprotein (P-gp) expressed at the Blood-Brain Barrier (BBB). Methods: To overcome the BBB obstacle, NLCs were used in this study as carriers for IDV, which were optimized through two steps: a “one-factor-at-a-time” screening followed by a systematic multiobjective optimization. Spherical smooth-surfaced Nanoparticles (NPs), average particle size of 161.02±4.8 nm, Poly-Dispersity Index (PDI) of 0.293±0.07, zeta potential of -40.62±2.21 mV, entrapment efficiency of 93±1.58%, and loading capacity of 9.15±0.15% were obtained after optimization which were, collectively, appropriate in terms of the objective of this study. Result: The surface of the optimized NPs was, then, modified with human Transferrin (TR) to improve the drug delivery. The particle size, zeta potential, and PDI of the TR-modified NLCs were 185.29±6.7nm, -28.68±3.37 mV, and 0.247±0.06, respectively. The in vitro release of IDV molecules from the NPs was best fitted to the Weibull model indicating hybrid diffusion/erosion behavior. Conclusion: As the major in vivo findings, compared to the free drug, the NLCs and TR-NLCs displayed significantly higher and augmented concentrations in the brain. In this case, NLC and TR-NLC were 6.5- and 32.75-fold in their values of the brain uptake clearance compared to free drug.

Formulation and Evaluation of Nanosuspension of Simvastatin

2015 ◽  
Vol 8 (2) ◽  
pp. 2858-2873
Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Factorial Design ◽  
Dissolution Rate ◽  
In Vitro Dissolution ◽  
Total Drug ◽  
23 Factorial Design ◽  
Rate Of Dissolution

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.

Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

2020 ◽  
Vol 26 ◽  
Author(s):  
John Chen ◽  
Andrew Martin ◽  
Warren H. Finlay
Keyword(s):  
Drug Delivery ◽  
In Silico ◽  
Local Drug Delivery ◽  
In Vivo Studies ◽  
Intranasal Drug Delivery ◽  
Nasal Sprays ◽  
In Silico Studies ◽  
Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

In vitro Lipolysis as a Tool for the Establishment of IVIVC for Lipid-Based Drug Delivery Systems

2019 ◽  
Vol 16 (8) ◽  
pp. 688-697
Author(s):  
Ravinder Verma ◽  
Deepak Kaushik
Keyword(s):  
Drug Delivery ◽  
Ph Value ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Rapid Screening ◽  
Resonance Spectroscopy ◽  
Fed State ◽  
In Vitro Lipolysis ◽  
Ph Stat

: In vitro lipolysis has emerged as a powerful tool in the development of in vitro in vivo correlation for Lipid-based Drug Delivery System (LbDDS). In vitro lipolysis possesses the ability to mimic the assimilation of LbDDS in the human biological system. The digestion medium for in vitro lipolysis commonly contains an aqueous buffer media, bile salts, phospholipids and sodium chloride. The concentrations of these compounds are defined by the physiological conditions prevailing in the fasted or fed state. The pH of the medium is monitored by a pH-sensitive electrode connected to a computercontrolled pH-stat device capable of maintaining a predefined pH value via titration with sodium hydroxide. Copenhagen, Monash and Jerusalem are used as different models for in vitro lipolysis studies. The most common approach used in evaluating the kinetics of lipolysis of emulsion-based encapsulation systems is the pH-stat titration technique. This is widely used in both the nutritional and the pharmacological research fields as a rapid screening tool. Analytical tools for the assessment of in vitro lipolysis include HPLC, GC, HPTLC, SEM, Cryo TEM, Electron paramagnetic resonance spectroscopy, Raman spectroscopy and Nanoparticle Tracking Analysis (NTA) for the characterization of the lipids and colloidal phases after digestion of lipids. Various researches have been carried out for the establishment of IVIVC by using in vitro lipolysis models. The current publication also presents an updated review of various researches in the field of in vitro lipolysis.

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