SELF-ASSEMBLED CHITOSAN NANOPARTICLES FOR PERCUTANEOUS DELIVERY OF CAFFEINE: PREPARATION, CHARACTERIZATION AND IN VITRO RELEASE STUDIES

Objective: Chitosan (CS)–tripolyphosphate (TPP)–nanoparticles (NPs) have been extensively studied during the past few decades due to their well-recognized applicability in various fields. The present study attempts to optimise the development of these nanoparticles to enhance the percutaneous delivery of caffeine.Methods: CS-TPP-NPs were prepared via ionic cross-linking of CS and TPP and were characterized. The influence of several formulation conditions (CS: TPP mass ratio and concentration of caffeine) and process parameters (stirring speed, stirring time and ultra-sonication time) on the colloidal characteristics of CS-TPP-NPs were investigated and the resulting nanoparticles were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) and x-ray diffraction (XRD) analyses. Physicochemical properties, including particle size, zeta potential and polydispersity index (PDI) were examined, and in vitro release studies were conducted to ascertain the release profile of caffeine from the nanoparticles. In addition, the colloidal stability of the prepared NPs was also assessed on storage.Results: Process parameters appeared to exert a significant effect on the physicochemical characteristics of the CS-TPP-NPs. The CS-TPP-NPs prepared under optimum conditions (CS concentration of 0.2 mg/ml, CS: TPP volume ratio of 25:12 ml, stirred at 700 rpm for 60 min, with 0.97 mg/ml caffeine concentration and treatment with low ultra-sonication for 30 min) had shown a mean particle size of ~143.43±1.69 nm, zeta potential of+43.13±1.10 mV, PDI of ~0.30±0.01. A drug loading capacity and encapsulation efficiency of 48.89% and 60.69%, respectively, were obtained. Cumulative release study for drug-loaded CS-NPs was significantly (p<0.001, paired t-test) higher (58.7% caffeine released) compared to control formulation (41.5% caffeine released) after 72 h. Stability studies conducted for 28 d showed that caffeine-loaded CS-NPs degraded much quicker when stored at 25 ⁰C than 4 ⁰C. It was also noted that caffeine-loaded CS-NPs in the freeze-dried form were unstable as the surface charge of nanoparticles dropped from positive zeta potential to-3.55 mV within 2 d at 4 ⁰C and at 25 ⁰C, surface charge dropped to-3.16 mV within 14 d of the experiment.Conclusion: Chitosan (CS)–tripolyphosphate (TPP)–nanoparticles (NPs) appear to be a promising strategy to achieve sustained percutaneous delivery of caffeine.

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Development of Intranasal Levothyroxine Powder Delivery for Hypothyroidism

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1689 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A828-A829

Author(s):

Syed Ali Imran ◽

Obinna Esomchukwu ◽

Remigius Agu

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Surface Morphology ◽

Freeze Drying ◽

Significant Proportion ◽

In Vitro Release ◽

X Ray ◽

Freeze Dried ◽

Vitro Release

Abstract Background: Hypothyroidism affects 3-5% of the general population with oral levothyroxine (LT4) being the predominant replacement therapy. However, significant proportion of hypothyroid patients are unable to absorb oral replacement leading to therapeutic failure and may require injectable thyroxine. Objectives: To develop non-invasive, less costly, and patient-friendly LT4 nasal delivery alternative using mucoadhesive polymers: chitosan and hydroxypropylmethylcellulose (HPMC). Methods: Six nasal LT4 formulations were developed with either chitosan or hydroxypropyl methylcellulose as mucoadhesive. The formulations were prepared through freeze-drying by varying the drug to polymer ratio (1:1, 1:3, and 1:5). The percentage drug yield was calculated by analyzing the weight of the formulation pre- and post-freeze drying. HPLC analysis was conducted to determine the amount of LT4 loaded in each formulation. Furthermore, the surface morphology, particle size, zeta potential, differential scanning calorimetry, X-ray diffraction as well as the in vitro release were assessed to determine the physicochemical properties and release characteristics of the formulations, respectively. Results: Both percentage drug loading and yield were > 70% for all the formulations. The freeze-dried formulations displayed a compact needle-like surface morphology. LT4-chitosan formulations, 1:1, 1:3, and 1:5 had mean particle size of 2.45 ± 0.88 µm, 2.76 ± 1.38 µm, and 1.59 ± 0.27 µm, respectively. Mean particle sizes for 1:1, 1:3, and 1:5 LT4-HPMC formulations were 0.56 ± 0.02 µm, 0.22 ± 0.06 µm, and 0.46 ± 0.04 µm. Zeta potential for LT4-chitosan formulation 1:1, 1:3, and 1:5 were -18.7 ± 1.00 mV, -16.2 ± 0.79 mV, and -19.17 ± 1.01 mV, respectively. LT4-HPMC 1:1, 1:3, and 1:5 formulations had zeta charges of -11.66 ± 3.16 mV, -6.06 ± 3.92 mV, and -9.53 ± 1.68 mV, respectively. Differential calorimetric analysis confirmed drug-polymer integration in all formulations, and X-ray powder diffraction showed both chitosan and HPMC formulations as crystalline configuration. The formulations with the highest in vitro release were LT4-HPMC 1:3 and LT4-chitosan 1:5. Conclusions: Results of this study suggest that both chitosan and HPMC can be used as sustained release polymers for the intranasal delivery of LT4.

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Preparation, Characterization and In-vitro release of Piroxicam-loaded Solid Lipid Nanoparticles

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2010.3.3.12 ◽

2010 ◽

Vol 3 (3) ◽

pp. 1136-1146

Author(s):

V K Verma ◽

Ram A

Keyword(s):

Electron Microscopy ◽

Particle Size ◽

Solid Lipid Nanoparticles ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Lipid Nanoparticles ◽

Diffusion Method ◽

Solid Lipid ◽

Vitro Release

Solid lipid nanoparticles (SLNs) of piroxicam where produced by solvent emulsification diffusion method in a solvent saturated system. The SLNs where composed of tripamitin lipid, polyvinyl alcohol (PVAL) stabilizer, and solvent ethyl acetate. All the formulation were subjected to particle size analysis, zeta potential, drug entrapment efficiency, percent drug loading determination and in-vitro release studies. The SLNs formed were nano-size range with maximum entrapment efficiency. Formulation with 435nm in particle size and 85% drug entrapment was subjected to scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for surface morphology, differential scanning calorimetry (DSC) for thermal analysis and short term stability studies. SEM and TEM confirm that the SLNs are nanometric size and circular in shape. The drug release behavior from SLNs suspension exhibited biphasic pattern with an initial burst and prolong release over 24 h.

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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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Development of nitazoxanide-loaded colon-targeted formulation for intestinal parasitic infections: centre composite design-based optimization and characterization

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-020-00130-1 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Charu Bharti ◽

Upendra Nagaich ◽

Jaya Pandey ◽

Suman Jain ◽

Neha Jain

Keyword(s):

Particle Size ◽

Desirability Function ◽

In Vitro Release ◽

Entrapment Efficiency ◽

In Vitro Drug Release ◽

Release Studies ◽

Percentage Yield ◽

Vitro Release ◽

Selection Of

Abstract Background The current investigation is focused on the development and characterization of Eudragit S100 coated nitazoxanide-loaded microbeads as colon-targeted system utilizing central composite design (CCD) and desirability function. The study initiated with the selection of a BCS class II drug nitazoxanide and its preformulation screening with excipients, selection of polymer and identification of concentration for CCD, selection of optimized formulation based on desirability function, and in vitro release studies in simulated gastric and colonic media and stability studies. A two-factor, three-level CCD was employed with two independent variables, i.e. X1 (chitosan % w/v) and X2 (sodium tripolyphosphate % w/v), and three dependent variables, i.e. Y1 (particle size in micrometres), Y2 (percentage yield) and Y3 (percent entrapment efficiency), were chosen. Additionally, surface morphology, mucoadhesion and in vitro drug release studies were also conducted. Result Chitosan concentration showing maximum entrapment and optimum particle size was selected to formulate chitosan beads. The polynomial equation and model graphs obtained from the Design-Expert were utilized to examine the effect of independent variables on responses. The effect of formulation composition was found to be significant (p ˂ 0.05). Based on the desirability function, the optimized formulation was found to have 910.14 μm ± 1.03 particle size, 91.84% ± 0.64 percentage yield and 84.75% ± 0.38 entrapment efficiency with a desirability of 0.961. Furthermore, the formulations were characterized for in vitro drug release in simulated colonic media (2% rat caecal content) and have shown a sustained release of ∼ 92% up to 24 h as compared to in vitro release in simulated gastric fluid. Conclusion The possibility of formulation in enhancing percentage yield and entrapment efficiency of nitazoxanide and the utilization of CCD helps to effectively integrate nitazoxanide microbeads into a potential pharmaceutical dosage form for sustained release.

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Sodium alginate nanoparticles as a new transdermal vehicle of glucosamine sulfate for treatment of osteoarthritis

European Journal of Nanomedicine ◽

10.1515/ejnm-2017-0008 ◽

2017 ◽

Vol 9 (3-4) ◽

Cited By ~ 2

Author(s):

Asmaa S. El-Houssiny ◽

Azza A. Ward ◽

Dina M. Mostafa ◽

Salwa L. Abd-El-Messieh ◽

Kamal N. Abdel-Nour ◽

...

Keyword(s):

Side Effects ◽

Surface Charge ◽

Ex Vivo ◽

In Vitro Release ◽

Glucosamine Sulfate ◽

Suspension Stability ◽

Rat Skin ◽

Release Studies ◽

Vitro Release

AbstractGlucosamine sulfate (GS) has been used orally for the treatment of osteoarthritis (OA). However, it may be susceptible to the liver first pass phenomenon, which greatly affects its bioavailability, in addition to its side effects on the gastrointestinal tract. Alginate nanoparticles (Alg NPs) were investigated as a new drug carrier for transdermal delivery of GS to improve its effectiveness and reduce side effects. GS-Alg NPs were characterized by encapsulation efficiency, NP yield, particle size and surface charge properties. The in vitro release studies of GS and the ex vivo permeability through rat skin were determined using a UV-Vis spectrophotometer. GS-Alg NPs are within the nanometer range of size. High negative surface charge values are obtained and indicate the high suspension stability of the prepared formulation. The in vitro release studies showed that GS is released from Alg NPs in a sustained and prolonged manner. The ex vivo permeability of GS through rat skin is enhanced significantly after encapsulation in the negatively charged Alg NPs. We successfully reported a highly stable nanoparticlulate system using Alg NPs that permits the encapsulation of GS for topical administration, overcoming the disadvantages of oral administration.

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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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FORMULATION OF POLYMERIC NANOSUSPENSION CONTAINING PRAMIPEXOLE DIHYDROCHLORIDE AND HESPERIDIN FOR IMPROVED TREATMENT OF PARKINSON’S DISEASES

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11s4.31721 ◽

2018 ◽

Vol 11 ◽

Author(s):

Somasundaram I

Keyword(s):

Particle Size ◽

Drug Release ◽

Zeta Potential ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Burst Release ◽

Drug Content ◽

Pramipexole Dihydrochloride ◽

Vitro Release

Aims and Objectives: The present study is to formulate the nanosuspension containing a hydrophilic drug pramipexole dihydrochloride and hesperidin and to increase the drug entrapment efficiency.Methods: Hesperidin and pramipexole dihydrochloride loaded in chitosan nanosuspension is prepared by ionic gelation method using chitosan and tripolyphosphate. There was no incompatibility observed between the drug and polymer through Fourier transform infrared and differential scanning calorimetric. Various other parameters such as particle size, zeta potential, scanning electron microscope, drug content, drug entrapment efficiency, and in vitro release have been utilized for the characterization of nanoparticles.Results and Discussion: The average size of particle is 188 nm; zeta potential is 46.7 mV; drug content of 0.364±0.25 mg/ml; entrapment efficiency of 72.8% is obtained with HPN3 formulation. The PHC1 shows the highest drug release followed by PHC2 due to low concentration of polymer and PHC4 and PHC5 show less drug release due to high concentration of polymer. The in vitro release of PHC3 is 85.2%, initial the burst release is shown which is approximately 60% in 8 h; then, slow release later on drastic reduction in release rate is shown in 24 h. The in vivo study histopathological report confers the effective protective against rotenone induces Parkinson’s.Conclusion: PHC3 was chosen as the best formulation due to its reduced particle size and controlled release at optimum polymer concentration which may be used to treat Parkinson’s disease effectively..

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FORMULATION AND IN VITRO EVALUATION OF CURCUMIN LOADED JACKFRUIT SEED STARCH NANOPARTICLES

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2020v12i6.40277 ◽

2020 ◽

pp. 32-35

Author(s):

JUNMONI NATH

Keyword(s):

Particle Size ◽

In Vitro Release ◽

Entrapment Efficiency ◽

In Vitro Drug Release ◽

Release Studies ◽

Infrared Studies ◽

Drug Entrapment Efficiency ◽

Starch Nanoparticles ◽

Vitro Release

Objectives: To meet the above aim the following objectives are undertaken: (1) Isolation of starch from jackfruit seeds and formulation of curcumin loaded jackfruit seed starch nanoparticles (2) In vitro evaluations of the drug loaded nanoparticles Methods: Jackfruit seed starch nanoparticles were prepared by Nanoprecipitation technique. In this technique, jackfruit seed starch was mixed with curcumin and acetone solution using a magnetic stirrer at 600 rpm. To the above solution, water were added dropwise and stirred at room temperature until acetone was completely vaporized. Nanoparticles were separated by centrifugation at 4000 rpm after 40 min. Results: Particle size of prepared nanoparticle formulations was found to be 371 to 411.72 nm with PDI of 0.148 to 0.356. The maximum % drug entrapment was found to be 57.34 % with formulation F5. In vitro release studies showed sustained release of drug till 12 h. Conclusion: The prepared nanoparticles were evaluated for its particle size, drug entrapment efficiency, in vitro drug release study, and surface morphology studies by scanning electron microscopy. The results of Fourier transform infrared studies of 1:1 physical mixture of drug and excipients confirmed the absence of incompatibility. Thus, the study concludes that curcumin loaded jackfruit seed starch nanoparticles were developed successfully by nanoprecipitation, which is expected to enhance the oral bioavailability of curcumin.

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ROSUVASTATIN CALCIUM LOADED CHITOSAN NANOPARTICLES: PREPARATION EVALUATION AND IN VITRO RELEASE STUDIES

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2020v12i5.38175 ◽

2020 ◽

pp. 95-102

Author(s):

SUVARNA G. BHOKARE ◽

RAJENDRA P. MARATHE

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Sustained Release ◽

Sodium Tripolyphosphate ◽

Chitosan Nanoparticles ◽

In Vitro Release ◽

Particle Diameter ◽

Vitro Release ◽

Rosuvastatin Calcium

Objective: The objective of the present study was to develop sustained release biodegradable polymeric nanoparticles of rosuvastatin calcium. Methods: Nanoparticles were prepared by modified ionotropic gelation method using 3² full factorial designs. From the preliminary trials, the constraints for independent variables X1 (concentration. of chitosan) and X2 (concentration. of sodium tripolyphosphate) have been fixed. Factors included concentration of chitosan and sodium tripolyphosphate, have been examined to investigate effect on particle size, encapsulation efficiency, zeta potential, % release, scanning electron microscopy, Fourier transfer infrared study and X-ray diffraction and release study of rosuvastatin calcium nanoparticles. 0 Results: The prepared nanoparticles were white, free-flowing and spherical in shape. The infrared spectra showed stable character of rosuvastatin calcium in the drug-loaded nanoparticles and revealed the absence of drug polymer interactions. The chitosan nanoparticles have a particle diameter ranging approximately 114.5±3.61 to 724±.2.51 nm and a zeta potential-13.12 to-52.63 mV. The in vitro release behavior from all the drug loaded batches were found to follow first order and provided sustained release over a period of 10 h. The Zeta potential of all the batches were in the range of-13.12 to-52.63 mv. The release profiles of all batches were very well fitted by Korsmeyer Peppas model. Conclusion: The best-fit release kinetics was achieved with Korsmeyer peppas model. The release of rosuvastatin calcium was influenced by the drug to polymer ratio and particle size. These results indicate that rosuvastatin calcium nanoparticles could be effective in sustaining drug release for a prolonged period.

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Preliminary studies on optimization of anti-parkinson drug loaded lipid nanoparticles enriched hydrogel formulations for management of Parkinson’s disease

Current Nanomedicine ◽

10.2174/2468187311666210311114908 ◽

2021 ◽

Vol 11 ◽

Author(s):

Kumara Swamy ◽

Ramesh Alli ◽

Thirupathi Gorre

Keyword(s):

Parkinson’S Disease ◽

Particle Size ◽

Parkinson's Disease ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Lipid Nanoparticles ◽

Release Studies ◽

Lipid Nanocarriers ◽

Vitro Release

Purpose: Ropinirole (RP), is a selective dopamine agonist that is used alone or with other medications to treat the symptoms of Parkinson’s disease (PD). RP has low bioavailability of only about 50% due to the first-pass metabolism, and it requires frequent dosing during oral administration. Aim: The objective of the current research was to develop RP loaded solid lipid nanoparticles (RP-SLNs), nanostructured lipid carriers (RP-NLCs), and their corresponding hydrogels (RP-SLN-C and RP-NLC-C) that could enhance RP therapeutic outcomes during PD treatment. Methods: RP nanoparticles were prepared by homogenization followed by probe sonication and optimized based on particle size, polydispersity index (PDI), zeta potential (ZP), % assay, % entrapment efficiency, and in vitro release studies. Optimized formulations were converted to hydrogel formulations using Carbopol 934 as a gelling polymer and optimized based on rheological and release characteristics. Optimized formulations were further evaluated using differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), freeze-drying, and stability study at refrigerated and room temperatures. Results: The optimized RP-SLN formulation showed particle size and entrapment efficiency of 213.5±3.8 nm and 77.9±3.1% compared to 190.6±3.7 nm and 85.7±1.7% for optimized RP-NLC formulation. PXRD supplemented and confirmed DSC results, RP was entrapped in a molecularly dispersed state inside the core of the lipid nanocarrier. Furthermore, RP loaded lipid nanocarriers revealed a spherical shape in SEM images. In vitro release studies demonstrated sustained release profiles for RP from SLNs, NLCs, and their hydrogels over 24 h. Optimized SLN, NLC, and nanocarrier loaded hydrogel formulations were stable over three months at 4ºC and 25ºC storage conditions. Conclusion: Overall, the results demonstrated that lipid nanocarriers and their corresponding hydrogel formulations can be considered as a topical drug delivery vehicle for RP during the treatment of PD.

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