Formulation and Optimization of Eudragit RS PO-Tenofovir Nanocarriers Using Box-Behnken Experimental Design

The objective of present study was to develop an optimized polymeric nanoparticle system for the antiretroviral drug tenofovir. A modified nanoprecipitation method was used to prepare Eudragit RS PO nanoparticles of the drug. The effect of amount of polymer, surfactant concentration, and sonication time on particle size, particle distribution, encapsulation efficiency (EE), and zeta potential were assessed and optimized utilizing a three-factor, three-level Box-Behnken Design (BBD) of experiment. Fifteen formulations of nanoparticles were prepared as per BBD and evaluated for particle size, polydispersity index (PDI), EE, and zeta potential. The results showed that the measured mean particle sizes were in the range of 233 to 499 nm, PDI ranged from 0.094 to 0.153, average zeta potential ranged from −19.9 to −45.8 mV, and EE ranged between 98 and 99%. The optimized formulation was characterized forin vitrodrug release and structural characterization. The mean particle size of this formulation was 233 nm with a PDI of 0.0107. It had a high EE of 98% and average zeta potential of −35 mV, an indication of particle stability. The FTIR showed some noncovalent interactions between the drug and polymer but a sustained release was observedin vitrofor up to 80 hours.

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Formulation of gel containing clotrimazole-loaded nanoparticles

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2019.5.3 ◽

2019 ◽

pp. 23-28

Author(s):

Hoang Nhan Ho ◽

Ngoc Tuan Hoang ◽

Thi Minh Nguyet Le

Keyword(s):

Particle Size ◽

Drug Release ◽

Topical Treatment ◽

Fungal Infections ◽

Topical Administration ◽

Sustained Drug Release ◽

Eudragit Rs ◽

Nanoprecipitation Method ◽

Drug Adverse Reaction

Background: Clotrimazole (CLO) is an imidazole derivative with antifungal activities. The conventional dosage forms for oral or topical administration have some disadvantages such as drug adverse reaction for long-term use, repeated doses daily due to short half-life. The aim of this study was to prepare gel containing CLO-loaded nanoparticles to increase drug solubility, enhance bioavailability, especially for a sustained drug release. Materials and methods: Eudragit RS 100 nanoparticles were prepared by the nanoprecipitation method, then was mixed with gel forming excipient. Gel containing CLO-loaded nanoparticles was characterized in terms of appearance, pH, particle size, PDI, encapsulation efficiency (EE), in vitro drug release. Results: The best formulation of gel containing 1% of CLO-loaded nanoparticles with 0.3% of Carbopol 934P, 5% of glycerin was smooth, homogenous, and particle size, PDI, EE, drug release of 154.6 ± 3.6 nm, 0.153 ± 0.011, 67.62 ± 0.89%, 51.46 ± 1.10% (after 24 hours). Conclusion: Gel containing CLO-loaded nanoparticles is a promising drug delivery system for the topical treatment of fungal infections. Key words: clotrimazole, Eudragit RS 100, fungal infection, nanoparticle, topical treatment

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PREPARATION AND IN VITRO EVALUATION OF METOPROLOL-LOADED BOVINE SERUM ALBUMIN NANOPARTICLES

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2021.v14i1.39738 ◽

2021 ◽

pp. 213-217

Author(s):

SHIVA KUMAR YELLANKI ◽

SAI MANOJ A ◽

MANGILAL T

Keyword(s):

Particle Size ◽

Bovine Serum Albumin ◽

Drug Release ◽

Zeta Potential ◽

Serum Albumin ◽

Bovine Serum ◽

Polymer Concentration ◽

Entrapment Efficiency ◽

Nanoprecipitation Method

Objective: The aim of the present research was to prepare metoprolol-loaded nanospheres. Metoprolol-loaded bovine albumin nanospheres were prepared by nanoprecipitation method. Metoprolol is beta-1-adrenergic receptor inhibitor specific to cardiac cells, thus producing negative chronotropic and ionotropic effect. Methods: Metoprolol nanospheres were prepared by nanoprecipitation method, using bovine serum albumin as polymer. The prepared nanospheres are evaluated for particle size evaluation, drug entrapment efficiency, and zeta potential. Drug-excipient compatibility was determined using Fourier-transform infrared spectroscopy. In vitro release and solubility of the drug from nanoparticles were determined. Results: The particle size of prepared metoprolol nanospheres was found to be always less than 200 nm. Maximum particle size was found to be 196±2.03 nm of batch 4 nanoparticles. Entrapment efficiency of prepared nanospheres was above 80% and maximum percentage entrapment efficiency was found to be 80.4±0.51%. It was found that the percentage entrapment efficiency and drug release were extended with increase in polymer concentration. Zeta potential of the optimized formulation was found to be −20.4 mV. In vitro drug release studies have shown the prolonged release of 94.5±0.54 up to 10 h. Drug release rate is extended with an increase in polymer concentration. Conclusion: Results have concluded that the albumin nanospheres loaded with metoprolol have reduced the blood pressure within 24 h and the prepared nanospheres are effective compared to other formulations and drug delivery.

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Formulation and Evaluation of Nanosuspension of Simvastatin

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2015.8.2.9 ◽

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.

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Optimization and Characterization of Aqueous Micellar Formulations for Ocular Delivery of an Antifungal Drug, Posaconazole

Current Pharmaceutical Design ◽

10.2174/1381612826666200313172207 ◽

2020 ◽

Vol 26 (14) ◽

pp. 1543-1555 ◽

Cited By ~ 2

Author(s):

Meltem E. Durgun ◽

Emine Kahraman ◽

Sevgi Güngör ◽

Yıldız Özsoy

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Size Distribution ◽

Encapsulation Efficiency ◽

Fungal Infections ◽

In Vitro Release ◽

Pluronic F127 ◽

Glycol Succinate ◽

Vitro Release

Background: Topical therapy is preferred for the management of ocular fungal infections due to its superiorities which include overcoming potential systemic side effects risk of drugs, and targeting of drugs to the site of disease. However, the optimization of effective ocular formulations has always been a major challenge due to restrictions of ocular barriers and physiological conditions. Posaconazole, an antifungal and highly lipophilic agent with broad-spectrum, has been used topically as off-label in the treatment of ocular fungal infections due to its highly lipophilic character. Micellar carriers have the potential to improve the solubility of lipophilic drugs and, overcome ocular barriers. Objective: In the current study, it was aimed optimization of posaconazole loaded micellar formulations to improve aqueous solubility of posaconazole and to characterize the formulations and to investigate the physical stability of these formulations at room temperature (25°C, 60% RH), and accelerated stability (40°C, 75% RH) conditions. Method: Micelles were prepared using a thin-film hydration method. Pre-formulation studies were firstly performed to optimize polymer/surfactant type and to determine their concentration in the formulations. Then, particle size, size distribution, and zeta potential of the micellar formulations were measured by ZetaSizer Nano-ZS. The drug encapsulation efficiency of the micelles was quantified by HPLC. The morphology of the micelles was depicted by AFM. The stability of optimized micelles was evaluated in terms of particle size, size distribution, zeta potential, drug amount and pH for 180 days. In vitro release studies were performed using Franz diffusion cells. Results: Pre-formulation studies indicated that single D-ɑ-tocopheryl polyethylene glycol succinate (TPGS), a combination of it and Pluronic F127/Pluronic F68 are capable of formation of posaconazole loaded micelles at specific concentrations. Optimized micelles with high encapsulation efficiency were less than 20 nm, approximately neutral, stable, and in aspherical shape. Additionally, in vitro release data showed that the release of posaconazole from the micelles was higher than that of suspension. Conclusion: The results revealed that the optimized micellar formulation of posaconazole offers a potential approach for topical ocular administration.

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Moxifloxacin Hydrochloride-Loaded Eudragit® RL 100 and Kollidon® SR Based Nanoparticles: Formulation, In vitro Characterization and Cytotoxicity.

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200428091945 ◽

2020 ◽

Vol 23 ◽

Cited By ~ 2

Author(s):

Gülsel Yurtdaş Kırımlıoğlu ◽

Sinan Özer ◽

Gülay Büyükköroğlu ◽

Yasemin Yazan

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Spray Drying ◽

Prolonged Release ◽

Ocular Delivery ◽

Corneal Permeability ◽

Release Pattern ◽

In Vitro Characterization ◽

Ocular Bioavailability

Background: Considering the low ocular bioavailability of conventional formulations used for ocular bacterial infection treatment, there’s a need for designing efficient novel drug delivery systems that may enhance of precorneal retention time and corneal permeability. Aim and Objective: The current research focuses on developing nanosized and non-toxic Eudragit® RL 100 and Kollidon® SR nanoparticles loaded with moxifloxacin hydrochloride (MOX) for its prolonged release to be promising for effective ocular delivery. Methods: In this study, MOX was incorporation was carried out by spray drying method aiming ocular delivery. In vitro characteristics were evaluated in detail with different methods. Results: MOX was successfully incorporated into Eudragit® RL 100 and Kollidon® SR polymeric nanoparticles by spray-drying process. Particle size, zeta potential, entrapment efficiency, particle morphology, thermal, FTIR, XRD and NMR analyses and MOX quantification using HPLC method were carried out to evaluate the nanoparticles prepared. MOX loaded nanoparticles demonstrated nanosized and spherical shape while in vitro release studies demonstrated modified release pattern which followed Korsmeyer-Peppas kinetic model. Following successful incorporation of MOX into the nanoparticles, the formulation (MOX: Eudragit® RL 100, 1:5) (ERL-MOX 2) was selected for further studies by the reason of its better characteristics like cationic zeta potential, smaller particle size, narrow size distribution and more uniform prolonged release pattern. Moreover, ERL-MOX 2 formulation remained stable for 3 months and demonstrated higher cell viability values for MOX. Conclusion: In vitro characterization analyses showed that non-toxic, nano-sized and cationic ERLMOX 2 formulation has the potential of enhancing ocular bioavailability.

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In Vitro Estimation of Photo-Protective Potential of Pomegranate Seed Oil and Development of a Nanoformulation

Current Nutrition & Food Science ◽

10.2174/1573401314666180223134235 ◽

2019 ◽

Vol 15 (1) ◽

pp. 87-102 ◽

Cited By ~ 2

Author(s):

Surbhi Dhawan ◽

Sanju Nanda

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Seed Oil ◽

Topical Delivery ◽

Inflammatory Activity ◽

Pomegranate Seed Oil ◽

Protective Potential ◽

Release Studies ◽

Pomegranate Seed

Background: Since ancient times, people have been using natural resources for photoprotection purposes. One such highly recognised natural agent is pomegranate seed oil, considered as wonder oil owing to the presence of several beneficial phytoconstituents. Objective: The study aimed to establish the photoprotective potential of pomegranate seed oil through various in vitro and biochemical studies along with the formation of nanoemulsion, an efficient topical delivery system for the oil. Method: Photo-protective potential of the oil was estimated by determining in vitro antioxidant and anti-inflammatory activity, total phenolic content, anti elastase, antihyaluronidase and anticollagenase activities of the oil. Ultrasonication method was used to formulate nanoemulsions. The optimisation was done following the central composite design. The characterisation was done by particle size analysis, zeta potential, polydispersity index, pH, viscosity, stability testing and transmission electron microscopy. The optimised nanoemulsion was loaded into a gel base for topical application and further release studies were carried out. Results: The IC50 values of anti-elastase, anti-collagenase and anti-hyaluronidase were found to be 309 mg/ml, 4 mg/ml and 95 mg/ml respectively. The results of anti-oxidant and anti-inflammatory activity were also significant, which thereby established the photo-protective potential of the oil. The optimum batch 2 had particle size 83.90 nm, 0.237 PDI and -5.37 mV zeta potential. The morphology was confirmed by TEM. Batch 2 was incorporated into a gel base and release studies showed 74.12 % release within 7 hours. Conclusion: Pomegranate seed oil possesses a potential photo-protective ability. Nanoemulsions proved to be a promising carrier for the topical delivery of the oil.

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PRAMIPEXOLE DIHYDROCHLORIDE LOADED MPEGPCL NANOSUSPENSION BY MODIFIED NANOPRECIPITATION: IN VITRO AND IN VIVO EVALUATION

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2016.v9i6.13979 ◽

2016 ◽

Vol 9 (6) ◽

pp. 161

Author(s):

Soma Sundaram

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Cell Viability ◽

Neuronal Damage ◽

Antioxidant Potential ◽

Enzymatic Antioxidants ◽

In Vivo Evaluation ◽

Neuroprotective Effects ◽

Pramipexole Dihydrochloride

AbstractAim and Objectives The present study was carried out to show the potential neuroprotective effects in both invitro and invivo pramipexole dihydrochloride nanosuspension for the treatment in Parkinson’s disease.Materials and Methods: Nanosuspension of pramipexole dihydrochloride was prepared with MPEG-PCL and Pluronic F68 by the process of modified nanoprecipitation technique with different concentrations of MPEG-PCL. The particle size, zeta potential, SEM, TEM and invitro dug release where performed. The cell viability study was performed by using SH-SY5Y cells. Further the formulation is evaluated for its antioxidant potential against rotenone induced neuronal damage in Wister rats such as enzymatic, non enzymatic antioxidants and histopathological evaluation.Result and Discussion: The nanoformulation shows least particle size of 143 nm and maximum zeta potential value 33.4 mv with 88.53% entrapment efficiency were observed with PMPNP 2 formulation. The SEM, TEM and invitro dug release of PMPNP 2 were shows spherical shape with controlled release when compared to other formulations. Further the MTT assay were performed by using SH-SY5Y cells which shows more than 50 % cell viability with 50 µl of PPMNP 2 nanoformulation. Further the antioxidant potential done in rotenone induced neuronal damage in Wister rats. The results showed elevation in the levels of enzymatic and non enzymatic antioxidants compared with neuronal toxic group. Further nanoformulation group showed decrease in levels of LPO which correlates with histopathological architecture.Conclusion: Our study concluded that nanoformulation showed better protective potential in both invitro and invivo compare to free drug for the treatment in Parkinson’s disease.Keywords: Pramipexoledihydrochloride; MPEG-PCL; SH-SY5Y cells; Nanoprecipitation; Parkinson’s disease.

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FORMULATION AND CHARACTERIZATION OF PAPAIN LOADED SOLID LIPID NANOPARTICLES AGAINST HUMAN COLORECTAL ADENOCARCINOMA CELL LINE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i10.27258 ◽

2018 ◽

Vol 11 (10) ◽

pp. 393

Author(s):

Suriyakala Perumal Chandran ◽

Kannikaparameswari Nachimuthu

Keyword(s):

Particle Size ◽

Drug Release ◽

Zeta Potential ◽

Cell Viability ◽

Cell Line ◽

Solid Lipid Nanoparticles ◽

Colorectal Adenocarcinoma ◽

Lipid Nanoparticles ◽

In Vitro Drug Release

Objective: Colorectal cancer is one of the most commonly diagnosed cancer and also most common gastrointestinal malignancy with high prevalence rate in the younger population. Usually, cancer cells are surrounded by a fibrin coat which is resistant to fibrinolytic degradation. This fibrin coat is act as self-protective against natural killing mechanism. The main objective was to prepare papain-loaded solid lipid nanoparticles (P-SLN) by melt dispersion-ultrasonication method and investigated the cytotoxic efficacy against colorectal adenocarcinoma (human colorectal adenocarcinoma [HCT 15]) cells.Methods: Optimized polymer ratio was characterized by differential scanning calorimetry, Fourier-transform infrared, X-ray diffraction, scanning electron microscopy, entrapment efficiency, particle size and zeta potential analysis, in vitro drug release, and in vitro cytotoxicity studies on HCT-15 colorectal adenocarcinoma cells.Results: The results showed that the particle size, morphological character and zeta potential value of optimized batch P-SLN were 265 nm, spherical and −26.5 Mv, respectively. The in vitro drug profile of P-SLN exhibited that it produced sustain drug release, and the cell viability of HCT-15 against P-SLN shown better efficacy than pure papain enzyme.Conclusion: P-SLNs were successfully prepared and investigated the in vitro drug release and in vitro cell viability against HCT-15 cell line.

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pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin

Pharmaceutics ◽

10.3390/pharmaceutics14010129 ◽

2022 ◽

Vol 14 (1) ◽

pp. 129

Author(s):

Hassan Shah ◽

Asadullah Madni ◽

Muhammad Muzamil Khan ◽

Fiaz-ud-Din Ahmad ◽

Nasrullah Jan ◽

...

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Release Rate ◽

In Vitro Release ◽

Chemotherapeutic Agents ◽

Ph Responsive ◽

Scanning Calorimetry ◽

Cholesteryl Hemisuccinate ◽

Vitro Release

The current study aimed to develop pH-responsive cisplatin-loaded liposomes (CDDP@PLs) via the thin film hydration method. Formulations with varied ratios of dioleoyl phosphatidylethanolamine (DOPE) to cholesteryl hemisuccinate (CHEMS) were investigated to obtain the optimal particle size, zeta potential, entrapment efficiency, in vitro release profile, and stability. The particle size of the CDDP@PLs was in the range of 153.2 ± 3.08–206.4 ± 2.26 nm, zeta potential was −17.8 ± 1.26 to −24.6 ± 1.72, and PDI displayed an acceptable size distribution. Transmission electron microscopy revealed a spherical shape with ~200 nm size. Fourier transform infrared spectroscopic analysis showed the physicochemical stability of CDDP@PLs, and differential scanning calorimetry analysis showed the loss of the crystalline nature of cisplatin in liposomes. In vitro release study of CDDP@PLs at pH 7.4 depicted the lower release rate of cisplatin (less than 40%), and at a pH of 6.5, an almost 65% release rate was achieved compared to the release rate at pH 5.5 (more than 80%) showing the tumor-specific drug release. The cytotoxicity study showed the improved cytotoxicity of CDDP@PLs compared to cisplatin solution in MDA-MB-231 and SK-OV-3 cell lines, and fluorescence microscopy also showed enhanced cellular internalization. The acute toxicity study showed the safety and biocompatibility of the developed carrier system for the potential delivery of chemotherapeutic agents. These studies suggest that CDDP@PLs could be utilized as an efficient delivery system for the enhancement of therapeutic efficacy and to minimize the side effects of chemotherapy by releasing cisplatin at the tumor site.

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IN VITRO ANTI-PLATELET AGGREGATION ACTIVITY OF HYDROXYPROPYL CELLULOSE–CYSTEAMINE BASED NANOPARTICLES CONTAINING CRUDE BROMELAIN

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2020v12i3.35053 ◽

2020 ◽

pp. 95-98

Author(s):

DENI RAHMAT ◽

LILIEK NURHIDAYATI ◽

MARCELLA MARCELLA ◽

ROS SUMARNY ◽

DIAN RATIH LAKSMITAWATI

Keyword(s):

Particle Size ◽

Platelet Aggregation ◽

Zeta Potential ◽

Light Transmission ◽

Hydroxypropyl Cellulose ◽

Platelet Activity ◽

Two Samples ◽

Significant Difference ◽

Aggregation Activity

Objective: The aim of the present study was to formulate bromelain into nanoparticles in order to improve its stability and activity. Methods: Crude bromelain was prepared by protein precipitation from the pineapple stem juice using ammonium sulphate at the concentration of 60% (w/v). Nanoparticles containing crude bromelain were generated using the ionic gelation method with hydroxypropyl cellulose–cysteamine (HPC-cysteamine) conjugate as a matrix. Crude bromelain was then added to the HPC-cysteamine solution for ionic interaction to construct the nanoparticles, which were then analyzed for their particle size and zeta potential. The resulting nanoparticles were mixed with adenosine diphosphate (ADP) to perform anti-platelet aggregation. Results: The nanoparticle had 928.3 nm in particle size and-7.25 mV in zeta potential. Anti-platelet activity of crude bromelain and the nanoparticles were determined with modification of light transmission aggregometry (LTA), in which ADP was used to induce an aggregation while a spectrophotometer UV-Vis was used to measure the absorbance at the wavelength of 600 nm. The result showed that crude bromelain and the nanoparticles rendered percentage inhibition of 8.00±1.17% and 48.56±11.19%, respectively. Conclusion: Based on the result of a one-way analysis of variance (ANOVA), it was concluded that there was a significant difference in percentage inhibition between the two samples. The nanoparticles demonstrated a better anti-platelet aggregation activity compared to crude bromelain.

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