Optimization of preparation conditions of poly(ε-caprolactone) microspheres for controlled release of carbamazepine

Poly (?-caprolactone), PCL, is an aliphatic polyester suitable for controlled drug release due to its biodegradability, biocompatibility, non-toxicity and high permeability to many therapeutic drugs. This study investigates the effect of the preparation parameters on the size and the morphology of the PCL microspheres and on the release profile of carbamazepine from these microspheres. The PCL microspheres were prepared using oil-in-water (o/w) emulsion solvent evaporation method with the poly(vinyl alcohol), PVA, as the emulsion stabilizer. The influence of the stirring rate applied during the emulsion formation, the homogenization time and the emulsifier concentration on diameter and size distribution of the microspheres was analyzed by scanning electron microscope (SEM). The initial emulsion was formed applying high stirring rates of 10000, 18000 and 23000 rpm, for homogenization times: 5, 10 and 15 min. The diameter was strongly influenced by the stirring rate, and the average particle size decreased from 9.2 to 2.8 ?m with the increase of the stirring rate. Increasing the amount of PVA in the water phase from 0.2 to 1 mass% improved stabilization of the oil droplets and led to a slight decrease of the average particle diameter. Drug-loaded microspheres were prepared by the same technique using different amounts of carbamazepine (10 and 15 mass%), under given conditions (1 mass% PVA, stirring rate of 18000 rpm for a period of 5 min of emulsion formation). Additionally, microspheres were prepared by applying low stirring rate of 1000 rpm with 10 and 15 mass% of the drug. The SEM analysis showed that microspheres created with 18000 rpm stirring rate, had average diameters of 3-4 ?m, and the microspheres prepared with 1000 rpm stirring rate were larger than 100 ?m. It was also observed that, in the case of the large microspheres, carbamazepine was deposited on their surfaces, while the small microspheres had smooth surfaces without observable drug crystals. The encapsulation efficiency and the release behavior of the carbamazepine were examined using high performance liquid chromatography-ultraviolet spectroscopy (HPLC-UV). The drug encapsulation efficiencies were in the range from 69 to 81%, and were increasing with the increase of the amount of carbamazepine in both series. In vitro release experiments were carried out in the phosphate buffer solution (pH 7) at 37?C. The release rate was influenced by the microspheres size and morphology. The larger microspheres released more carbamazepine (85-95%) compared to the small ones (50-65%) for the same period. This behavior was attributed to the different drug distribution in the PCL matrix. Different mathematical models were used to describe drug release kinetics. It was concluded that the mechanism of the carbamazepine release from the microspheres was diffusion-controlled, independent on the type of microspheres. The kinetic parameters showed that the release of carbamazepine was slower from the smaller microspheres, probably as a result of more even distribution of the drug in the polymer matrix.

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Preparation of biodegradable porous poly(butylene succinate) microspheres

Hemijska industrija ◽

10.2298/hemind0806329p ◽

2008 ◽

Vol 62 (6) ◽

pp. 329-338 ◽

Cited By ~ 2

Author(s):

Dragana Pepic ◽

Milica Spasojevic ◽

Marija Nikolic ◽

Jasna Djonlagic

Keyword(s):

Particle Size ◽

Apparent Density ◽

Average Particle Size ◽

Phosphate Buffer Solution ◽

Poly Vinyl Alcohol ◽

Average Particle ◽

Optimal Conditions ◽

Butylene Succinate ◽

Porous Microspheres ◽

Stirring Rate

The aim of this study was to determine the optimal conditions for the fabrication of porous microspheres based on poly(butylene succinate), PBS. The biodegradable non-porous PBS microspheres were prepared by the oil-in-water (o/w) emulsion solvent evaporation method using poly(vinyl alcohol), PVA, as the surfactant. Fabrication conditions, such as stirring rate, organic/aqueous ratio, PBS concentration and surfactant (PVA) concentration, which have an important influence on both the particle size and the morphology of the microspheres, were varied. Scanning electron microscopy, SEM, observations confirmed the size, size distribution and surface morphology of the microspheres. The optimal conditions for the preparation of the non-porous microspheres were found to be: concentration the PBS solution, 10 mass%; PVA concentration, 1 mass%; the organic/ aqueous ratio CHCl3/H2O = 1/20 and stirring rate 800 rpm. Porous PBS microspheres were fabricated under the optimal conditions using various amounts of hexane and poly(ethylene oxide), PEO, as porogens. The influence of the amount of porogen on the pore size and the particle size was investigated using SEM and the apparent density. The microspheres exhibited various porosities and the pore sizes. The average particle size of the microspheres with PEO as the porogen was from 100 to 122?m and that of the microspheres with hexane as the porogen was from 87 to 97?m. The apparent density of the porous microspheres with PEO as the porogen, from 0.16 to 0.23 g/cm3, was much smaller than the non-porous microspheres, 0.40 g/cm3. In the in vitro degradation experiments, the porous microspheres were incubated in phosphate buffer solution (pH 7) at 37?C. After incubating for one month, the microspheres showed significant extent of the hydrolytic degradation of the porous PBS microspheres.

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Mesoporous Silica Nanoparticles of Hydroxyurea: Potential

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681210999200430010457 ◽

2020 ◽

Vol 10 ◽

Author(s):

Kumar Nishchaya ◽

Swatantra K.S. Kushwaha ◽

Awani Kumar Rai

Keyword(s):

Drug Release ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Release Kinetics ◽

Average Particle Size ◽

Silica Nanoparticle ◽

Average Particle ◽

Independent Variables ◽

Lower Temperature

Background: Present malignant cancer medicines has the advancement of magnetic nanoparticles as delivery carriers to magnetically accumulate anticancer medication in malignant growth tissue. Aim: In the present investigation, a silica nanoparticles (MSNs) stacked with hydroxyurea were combined and was optimized for dependent and independent variables. Method: In this study, microporous silica nanoparticle stacked with neoplastic medication had been prepared through emulsification followed with solvent evaporation method. Prepared MSNs were optimized for dependent and independent variables. Different formulations were prepared with varying ratio of polymer, lipid and surfactant which affects drug release and kinetics of drug release pattern. The obtained MSNs were identified by FTIR, SEM, drug entrapment, in-vitro drug release, drug release kinetics study, stability testing in order to investigate the nanoparticle characteristics. Results: The percentage drug entrapment of the drug for the formulations F1, F2, F3, was found to be 27.78%, 65.52% and 48.26%. The average particle size for F2 formulation was found to be 520 nm through SEM. The cumulative drug release for the formulations F1, F2, F3 was found to be 64.17%, 71.82% and 32.68%. The formulations were found to be stable which gives controlled drug delivery for 6 hours. Conclusion: From the stability studies data it can be culminated that formulations are most stable when stored at lower temperature or in refrigerator i.e. 5˚C ± 3˚C. It can be concluded that MSN’s loaded with hydroxyurea is a promising approach towards the management of cancer due to its sustained release and less side effects.

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Drug-loaded ultrafine poly(vinyl alcohol) fibre mats prepared by electrospinning

e-Polymers ◽

10.1515/epoly.2005.5.1.750 ◽

2005 ◽

Vol 5 (1) ◽

Cited By ~ 4

Author(s):

Chunxue Zhang ◽

Xiaoyan Yuan ◽

Lili Wu ◽

Jing Sheng

Keyword(s):

Drug Release ◽

Photoelectron Spectroscopy ◽

Vinyl Alcohol ◽

Phosphate Buffer Solution ◽

Poly Vinyl Alcohol ◽

High Porosity ◽

Buffer Solution ◽

Drug Molecules ◽

Alcohol Fibre

AbstractSubmicron poly(vinyl alcohol) (PVA) fibre mats embedded with Aspirin and bovine serum albumin (BSA) were prepared by electrospinning of their aqueous solutions. Fibre morphology was investigated by scanning electron microscopy. The composition of the fibre mats was characterized by Fourier transform IR spectroscopy and X-ray photoelectron spectroscopy. The in vitro drug release was investigated by immersing the fibre mats in phosphate buffer solution at 37°C. Results indicated that the morphology of fibre mats was influenced by the amount of drug, and more beaded and irregularly shaped fibres were found with increasing drug amounts. There were drug molecules distributed on the surface of the PVA fibres. Studies of in vitro drug release showed that both Aspirin and BSA were released more quickly from PVA fibre mats than from PVA films because of the large surface area and high porosity of the fibre mats.

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Preparation, characterization, and in vitro evaluation of amphiphilic peptide P12 and P12-DOX nanomicelles as antitumor drug carriers

Nanomaterials and Nanotechnology ◽

10.1177/1847980420911519 ◽

2020 ◽

Vol 10 ◽

pp. 184798042091151 ◽

Cited By ~ 1

Author(s):

Ping Song ◽

Wuchen Du ◽

Wanzhen Li ◽

Longbao Zhu ◽

Weiwei Zhang ◽

...

Keyword(s):

Particle Size ◽

Drug Release ◽

Solid Phase ◽

Average Particle Size ◽

In Vitro Release ◽

Drug Carriers ◽

Average Particle ◽

Polymer Micelles ◽

Amphiphilic Peptide

Polymerized polypeptide nanomicelles have attracted much attention as novel drug carriers because of their good biocompatibility and degradability. To prepare doxorubicin (DOX)-loaded nanomicelles, an amphiphilic peptide, FFHFFH-KKGRGD (P12), was synthesized by solid-phase synthesis, and the physicochemical and drug-release properties, as well as the cytotoxicity of the nanomicelles, were evaluated in vitro. The P12-DOX polymer micelles were prepared by dialysis. The morphology and particle size were characterized by transmission electron microscopy and dynamic light scattering. The critical micelle concentration (CMC) of the polymer was determined by the probe method, and the drug-release characteristics of the micelles were studied by dynamic dialysis. The cytotoxicity and uptake of the P12-DOX micelles were evaluated against mouse breast cancer cells (4T1) and human umbilical vein endothelial cells. The peptide polymer micelles containing DOX were uniformly sized and had a spherical core–shell structure with an average particle size of 128.6 nm. The CMC of the polymer was low (0.0357 mg/mL). The in vitro release of DOX from the micelles is slow and is consistent with first-order kinetics. The copolymer micelles of the P12 polypeptide and DOX can be used as nanoscale spherical carriers of hydrophobic drugs and have broad applicability.

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Olanzapine Loaded Nanostructured Lipid Carriers via High Shear Homogenization and Ultrasonication

Scientia Pharmaceutica ◽

10.3390/scipharm89020025 ◽

2021 ◽

Vol 89 (2) ◽

pp. 25

Author(s):

Adejumoke Lara Ajiboye ◽

Uttom Nandi ◽

Martin Galli ◽

Vivek Trivedi

Keyword(s):

Particle Size ◽

Drug Release ◽

Drug Loading ◽

Particle Diameter ◽

Phosphate Buffer Solution ◽

Nanostructured Lipid Carriers ◽

High Shear ◽

Buffer Solution ◽

High Shear Homogenization

The aim of this study was to understand the effect of high shear homogenization (HSH) and ultrasonication (US) on the physicochemical properties of blank and olanzapine loaded nanostructured lipid carriers (NLCs) along with their drug loading potential and drug release profiles from formulated particles. NLCs were prepared with different ratios of Compritol and Miglyol as the solid and liquid lipids, respectively, under changing HSH and US times between 0 to 15 minutes. The surfactants (Poloxamer 188 (P188) and tween 80) and the drug content was kept constant in all formulations. The prepared NLCs were evaluated for particle size, polydispersity index, zeta potential, drug crystallinity and chemical interactions between lipids and OLZ. The in-vitro drug release was performed using dialysis tube method in phosphate buffer solution (PBS) at pH 7.4. The formulated NLCs were negatively charged, spherically shaped and monodisperse, with particle sizes ranging from 112 to 191 nm. There was a significant influence of US time on the preparation of NLCs in comparison to HSH, where a significant reduction in the mean particle diameter was seen after 5 min of sonication. An increase of Miglyol content in NLCs led to an increase in particle size. In general, application of US led to decrease in particle size after HSH but an increase in particle diameter of low Miglyol containing preparation was also observed with longer sonication time. OLZ was successfully encapsulated in the NLCs and a total release of 89% was achieved in 24 hours in PBS at pH 7.4.

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Poly(vinyl alcohol)/chitosan hydrogels with electrochemically synthesized silver nanoparticles for wound dressing applications

Journal of Electrochemical Science and Engineering ◽

10.5599/jese.732 ◽

2020 ◽

Vol 10 (2) ◽

pp. 185-198 ◽

Cited By ~ 2

Author(s):

Katarina Nešović ◽

Ana Janković ◽

Tamara Radetić ◽

Aleksandra Perić-Grujić ◽

Maja Vukašinović-Sekulić ◽

...

Keyword(s):

Silver Nanoparticles ◽

Wound Dressing ◽

Release Kinetics ◽

Phosphate Buffer Solution ◽

Wound Dressings ◽

Poly Vinyl Alcohol ◽

Burst Release ◽

Buffer Solution ◽

Sorption Ability ◽

Conventional Antibiotics

Polymer-based hydrogel materials are excellent candidates for new-generation wound dressings with improved properties, such as high sorption ability, good mechanical properties and low adhesiveness. Cross-linked hydrogel matrices also serve as excellent carriers for controlled release of antibacterial agents, such as silver nanoparticles (AgNPs), which are preferred over conventional antibiotics due to low propensity to induce bacterial resistance. In this work, we aim to produce novel silver/poly(vinyl alcohol)/chitosan (Ag/PVA/CHI) hydrogels for wound dressing applications. The electrochemical AgNPs synthesis provided facile and green method for the reduction of Ag+ ions inside the hydrogel matrices, without the need to use toxic chemical reducing agents. The formation of AgNPs was confirmed using UV-visible spectroscopy, scanning and transmission electron microscopy. Release kinetics was investigated in modified phosphate buffer solution at 37 °C to mimic physiological conditions. Release profiles indicated “burst release” behavior, which is beneficial for wound dressing applications. The antibacterial activity was evaluated against Staphylococcus aureus and Escherichia coli strains using disc-diffusion test, and non-toxicity of hydrogels was proved by dye-exclusion test. The obtained results confirmed strong potential of Ag/PVA/CHI hydrogels for biomedical applications.

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Formulation and Evaluation of Ketoconazole Nanosponge gel

Journal of University of Shanghai for Science and Technology ◽

10.51201/jusst12645 ◽

2021 ◽

Vol 23 (2) ◽

Author(s):

Vijay R Chakote ◽

◽

Ms.Deepali R. Wagh ◽

Mr. Rahul S. Waghmare ◽

Umesh T. Jadhao ◽

...

Keyword(s):

Particle Size ◽

Drug Release ◽

Average Particle Size ◽

In Vitro Release ◽

Average Particle ◽

Sustained Drug Release ◽

Percentage Yield ◽

Viscosity Study ◽

Cross Linker

Ketoconazole Nanosponges were prepared by using Hyper cross linked β-cyclodextrin method by using different concentration of cross-linker. Diphenyl carbonate was used as the cross linking polymer. Nanosponge formulations were prepared by using β-CD: cross linker ratios of 1:15, 1:10, 1:5 and 1:3.Thepreparednanosponges were evaluated for percentage yield, incorporation efficiency, particle size, drug polymer compatibility, scanning electron microscopy andin-vitrodrugrelease.SEM studies confirmed their porous structure with number of nano channels. The FTIR spectra showed stable character of Ketoconazole in mixture of polymers and revealed the absence of drug polymer interactions. DSC study revealed that drug was involved in complexation with nanosponges. The average particle size of Ketoconazole nanoparticles was found to be in the range of 78.81± 0.20 nm to336.02 ± 0.124nm.The drug release from nanosponges was found to extended upto 8hr. 82 to 92%.The nano sponges were formulated into gel using Carbopol 940Batches G1 to G4 were prepared by incorporating nanosponges equivalent to 6%w/w of ketoconazole in different polymer concentrations respectively and evaluated for Percent drug content, Viscosity study, Spreadability study, In vitro diffusion studies. Nanosponge gel G1 showed the optimum pH, viscosity, Spread ability and In vitro release. Drug diffusion from the nanosponge loaded gel formulations was show sustained rate. A sustained release topical drug delivery of Ketoconazole developed as a nanosponge loaded gel offers solubilizing matrix for the drug, served as a local depot for sustained drug release and provided a rate limiting matrix barrier for modulation of drug release.

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PREPARATION AND EVALUATION OF CONTROLLED RELEASE FLOATING MICROSPHERES OF REPAGLINIDE: OPTIMIZATION AND IN-VITRO STUDIES

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i3.15310 ◽

2017 ◽

Vol 10 (3) ◽

pp. 103 ◽

Cited By ~ 1

Author(s):

Megha Sharma ◽

Seema Kohli ◽

Abhisek Pal

Keyword(s):

Drug Release ◽

Hydroxypropyl Methylcellulose ◽

Average Particle Size ◽

In Vitro Release ◽

Kinetic Studies ◽

Entrapment Efficiency ◽

Gastric Fluid ◽

Appreciable Amount ◽

Average Particle

ABSTRACTObjective: To develop and evaluate floating microspheres of repaglinide (RG).Materials and Methods: RG loaded noneffervescent microspheres of different ratios of ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMCK4M) were prepared using polyvinyl alcohol as emulsifier by solvent evaporation technique. Various process variables such as polymer ratio, stirringspeed, concentration of drug, and emulsifying agent were studied. Compatibility of drug and polymers was studied by Fourier-transform infraredspectroscopy (FTIR). Characterization, in-vitro evaluation, and kinetic studies were performed.Results: FTIR spectra have revealed no drug-excipient incompatibility. The average particle size of microspheres was in the range of 312-359 μm. Theresults showed that floating microspheres were successfully prepared with good yield (56.15-64.3%), high entrapment efficiency (58.22-70.14%),and good floating behavior (63.1-76.2%), respectively. In-vitro release data indicates appreciable amount of drug is released (62.28-73.27%) from themicrospheres in gastric fluid. The mechanism of drug release founds to follow first order kinetics (r2=0.986).Conclusion: The developed floating microspheres of RG may be used for prolonged drug release for at least 12 hrs, thereby improving bioavailabilityand patient compliance.Keywords: Repaglinide, Compatibility, Kinetic, Ethylcellulose.

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FORMULATION, CHARACTERIZATION AND IN VITRO EVALUTION OF GABAPENTIN FLOATING MICROSPHERES

INDIAN DRUGS ◽

10.53879/id.54.01.10598 ◽

2017 ◽

Vol 54 (01) ◽

pp. 20-27

Author(s):

H. B Samal ◽

I. J. Das ◽

P. N. Murthy ◽

Keyword(s):

Particle Size ◽

Drug Release ◽

Release Kinetics ◽

Polymer Concentration ◽

Average Particle Size ◽

Entrapment Efficiency ◽

Linear Regression Method ◽

Average Particle ◽

Drug Entrapment Efficiency

The present study involves the design and characterization of floating microspheres with gabapentin as model drug for prolongation of gastric residence time. Gabapentin floating microspheres were prepared by o/w/o emulsification solvent diffusion technique using ethyl cellulose as the rate controlling polymer at various concentrations. The shape and surface morphology of microspheres were characterized by optical and scanning electron microscopy. Absence of drug-polymer interaction was confirmed by FTIR analysis. In vitro drug release studies were performed and drug release kinetics was evaluated using the linear regression method. Effects of polymer concentration, solvent composition, particle size, drug entrapment efficiency and drug release were also studied. The synthesized microspheres exhibited prolonged drug release (> 12 h) and remained buoyant for > 24 h. The drug entrapment efficiency was in the range 46-70 %. At higher polymer concentration, the average particle size was increased and the drug release rate decreased. In vitro studies revealed diffusion-controlled drug release from the microspheres. Among all the formulations (F1-F5), F4 is the optimized formulation.

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Formulating SLN and NLC as Innovative Drug Delivery Systems for Non-Invasive Routes of Drug Administration

Current Medicinal Chemistry ◽

10.2174/0929867326666190624155938 ◽

2020 ◽

Vol 27 (22) ◽

pp. 3623-3656 ◽

Cited By ~ 1

Author(s):

Bruno Fonseca-Santos ◽

Patrícia Bento Silva ◽

Roberta Balansin Rigon ◽

Mariana Rillo Sato ◽

Marlus Chorilli

Keyword(s):

Drug Delivery ◽

Particle Size ◽

Drug Release ◽

Drug Loading ◽

Average Particle Size ◽

Delivery Systems ◽

Average Particle ◽

Minor Importance ◽

Routes Of Administration ◽

Non Invasive

Colloidal carriers diverge depending on their composition, ability to incorporate drugs and applicability, but the common feature is the small average particle size. Among the carriers with the potential nanostructured drug delivery application there are SLN and NLC. These nanostructured systems consist of complex lipids and highly purified mixtures of glycerides having varying particle size. Also, these systems have shown physical stability, protection capacity of unstable drugs, release control ability, excellent tolerability, possibility of vectorization, and no reported production problems related to large-scale. Several production procedures can be applied to achieve high association efficiency between the bioactive and the carrier, depending on the physicochemical properties of both, as well as on the production procedure applied. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes Lipid-based nanocarriers (LNCs) versatile delivery system for various routes of administration. The route of administration has a significant impact on the therapeutic outcome of a drug. Thus, the non-invasive routes, which were of minor importance as parts of drug delivery in the past, have assumed added importance drugs, proteins, peptides and biopharmaceuticals drug delivery and these include nasal, buccal, vaginal and transdermal routes. The objective of this paper is to present the state of the art concerning the application of the lipid nanocarriers designated for non-invasive routes of administration. In this manner, this review presents an innovative technological platform to develop nanostructured delivery systems with great versatility of application in non-invasive routes of administration and targeting drug release.

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