Development, Characterization, and Evaluation of SLN-Loaded Thermoresponsive Hydrogel System of Topotecan as Biological Macromolecule for Colorectal Delivery

Background. Chemotherapeutic drugs cause severe toxicities if administered unprotected, without proper targeting, and controlled release. In this study, we developed topotecan- (TPT-) loaded solid lipid nanoparticles (SLNs) for their chemotherapeutic effect against colorectal cancer. The TPT-SLNs were further incorporated into a thermoresponsive hydrogel system (TRHS) (TPT-SLNs-TRHS) to ensure control release and reduce toxicity of the drug. Microemulsion technique and cold method were, respectively, used to develop TPT-SLNs and TPT-SLNs-TRHS. Particle size, polydispersive index (PDI), and incorporation efficiency (IE) of the TPT-SLNs were determined. Similarly, gelation time, gel strength, and bioadhesive force studies of the TPT-SLNs-TRHS were performed. Additionally, in vitro release and pharmacokinetic and antitumour evaluations of the formulation were done. Results. TPT-SLNs have uniformly distributed particles with mean size in nanorange (174 nm) and IE of ~90%. TPT-SLNs-TRHS demonstrated suitable gelation properties upon administration into the rat’s rectum. Moreover, drug release was exhibited in a control manner over an extended period of time for the incorporated TPT. Pharmacokinetic studies showed enhanced bioavailability of the TPT with improved plasma concentration and AUC. Further, it showed significantly enhanced antitumour effect in tumour-bearing mice as compared to the test formulations. Conclusion. It can be concluded that SLNs incorporated in TRHS could be a potential source of the antitumour drug delivery with better control of the drug release and no toxicity.

Download Full-text

Stomach-Specific Drug Delivery of Clarithromycin Using aSemi Interpenetrating Polymeric Network Hydrogel Made ofMontmorillonite and Chitosan: Synthesis, Characterization and InVitro Drug Release Study

Advanced Pharmaceutical Bulletin ◽

10.15171/apb.2019.019 ◽

2019 ◽

Vol 9 (1) ◽

pp. 159-173 ◽

Cited By ~ 5

Author(s):

Yunes Panahi ◽

Afshin Gharekhani ◽

Hamed Hamishehkar ◽

Parvin Zakeri-Milani ◽

Hamed Gharekhani

Keyword(s):

Drug Delivery ◽

Hydrochloric Acid ◽

Drug Release ◽

Polymer Network ◽

In Vitro Release ◽

Extended Period ◽

Interpenetrating Polymer Network ◽

Swelling Kinetic ◽

Hydrogel Nanocomposite

Purpose: In this study, we aimed to prepare an extended drug delivery formulation ofclarithromycin (CAM) based on a semi-interpenetrating polymer network (semi-IPN) hydrogel.Methods: Synthesis of semi-IPN hydrogel nanocomposite made of chitosan (CS), acrylicacid (AA), acrylamide (AAm), polyvinylpyrrolidone (PVP), and montmorillonite (MMT) wasperformed by free radical graft copolymerization method. Swelling kinetic studies were done inacidic buffer solutions of hydrochloric acid (pH = 1.2), acetate (pH = 4), and also distilled water.Also, the effects of MMT on the swelling kinetic, thermal stability, and mechanical strengthof the hydrogels were evaluated. Moreover, in vitro release behavior of CAM and its releasekinetics from hydrogels were studied in a hydrochloric acid buffer solution.Results: Fourier transform infrared spectroscopy (FTIR) results revealed that synthesis of semi-IPN superabsorbent nanocomposite and CAM incorporation into hydrogel was performed,successfully. Introducing MMT into hydrogel network not only improved its thermal stabilitybut also increased mechanical strength of the final hydrogel product. Also, in comparisonwith neat hydrogel (1270 g/g), hydrogel nanocomposite containing 13 wt% MMT exhibitedgreater equilibrium swelling capacity (1568 g/g) with lower swelling rate. In vitro drug releaseexperiments showed that CS-g-poly(AA-co-AAm)/PVP/MMT/CAM formulation possesses asustained release character over extended period of time compared with CS-g-poly(AA-co-AAm)/PVP/CAM formulation.Conclusion: In the presence of MMT, the effective life time of drug is prolonged, demonstrating asustained release property. The reason is that interlinked porous channels within superabsorbentnanocomposite network hinder penetration of aqueous solutions into hydrogel and subsequentlycause a slower drug release.

Download Full-text

Preparation of Poly(vinyl alcohol)/Polyoxalate Composite Nanofibers by Electrospinning and Drug Release Profiles

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.894.369 ◽

2014 ◽

Vol 894 ◽

pp. 369-373

Author(s):

Nutthakritta Phromviyo ◽

Ekaphan Swatsitang ◽

Apiwat Chompoosor

Keyword(s):

Drug Release ◽

Rhodamine B ◽

Vinyl Alcohol ◽

In Vitro Release ◽

Control Release ◽

Electrospun Nanofibers ◽

Average Diameter ◽

Poly Vinyl Alcohol ◽

Electrospinning Technique

This study investigated the use of a biodegradable polyoxalate blended with poly (vinyl alcohol) nanofibers to tailor properties of nanofibers and to control release of Rhodamine B from nanofibers. Nanofibers were prepared using an electrospinning technique. The morphology and average diameter of electrospun nanofibers were investigated using scanning electron microscopy. It was found that poly (vinyl alcohol) to polyoxalate ratio had a significant effect on the size of nanofibers (~175-403 nm). An in vitro release study showed that rate of Rhodamine B release increased with increasing poly (vinyl alcohol)/polyoxalate ratios yielding rate of release in the range of 0.1980.469 mg%/min. The mechanism of rhodamine B release can be explained by a two-stage process of diffusion and degradation. The results suggested that a water-insoluble polyoxalate could govern the rate of drug release. The ability to tune the release of chemicals from nanofibers has significant implications for controlled release of drugs.

Download Full-text

Formulation and Pharmacokinetic Evaluation of Microcapsules Containing Pravastatin Sodium Using Rats

Scientifica ◽

10.1155/2016/7623193 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9

Author(s):

Venkatesh Dinnekere Puttegowda ◽

Roopa Karki ◽

Divakar Goli ◽

Sajal kumar Jha ◽

Manjunatha Panduranga Mudagal

Keyword(s):

Drug Release ◽

Chemical Interaction ◽

Control Release ◽

Pharmacokinetic Studies ◽

Nonaqueous Solvent ◽

Stability Studies ◽

X Ray Diffraction ◽

Pravastatin Sodium ◽

Pharmacokinetic Evaluation

Pravastatin Sodium has a cholesterol lowering agent. It has shorter half-life and undergoes first-pass metabolism. Frequent dose is required in case of conventional dosage form. The purpose of the study is to formulate and evaluate microcapsules containing Pravastatin Sodium by complex with cholestyramine resins coated with Eudragit RLPO and Eudragit RSPO polymers for achieving control release. Complexation of drug on resin was carried out by batch method. Microencapsulation was carried out by nonaqueous solvent evaporation method. Pharmacokinetic studies were done by using rats. The intermediate stability studies were carried out on the most satisfactory formulations. FTIR, X-ray diffraction, and DSC spectra of drug, drug-resinates, and polymers revealed no chemical interaction. The % DEE and % yield were observed for formulations of f1 to f7 that were varied from 97.1 ± 0.8 to 98.9 ± 0.5% and 95.0 ± 3.25 to 98.8 ± 7.1%, respectively. Most satisfactory formulation, f6, showed drug release up to 72.6%. No changes in % DEE and % CDR were observed after stability studies. Microcapsules of f6 formulation achieved best performance regardingin vitrodrug release and from pharmacokinetic evaluation mean residence time was found to be 6.3 h, thus indicated, Pravastatin Sodium microcapsules were released and absorbed slowly over a prolonged period of time.

Download Full-text

Formulation and In vitro Release Characterization of Metoprolol Succinate Extended Release Tablets

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2011.4.4.3 ◽

2012 ◽

Vol 4 (4) ◽

pp. 1537-1543

Author(s):

Sakthikumar T ◽

Rajendran N N ◽

Natarajan R

Keyword(s):

Drug Release ◽

Extended Release ◽

In Vitro Release ◽

Methyl Cellulose ◽

Wet Granulation ◽

Direct Compression ◽

Metoprolol Succinate ◽

Extended Release Formulations ◽

Vitro Release

The present study was aimed to develop an extended release tablet of metoprolol Succinate for the treatment of hypertension. Four extended release formulations F1-F4 were developed using varying proportions of hydroxylpropyl-methylcellulose K100M, sodium carboxy methyl cellulose and Eudragit L30 D55 by wet granulation. Five extended release formulations F5-F9 containing HPMC K100M and HPMC 5 cps in varying concentration were developed by direct compression. The physicochemical and in vitro release characteristics of all the formulations were investigated and compared. Two formulations, F7 and F8 have shown not more 25% drug release in 1st h, 20%-40% drug release at 4th hour, 40%-60% drug release at 8th hour and not less than 80% at 20th hour and the release pattern conform with USP specification for 24 hours extended release formulation. It can be conclusively stated that optimum concentration of HPMC K100M (58%-65%) by direct compression method can yield an extended release of metoprolol succinate for 24 hours.

Download Full-text

Design, Synthesis and Studies on Novel Polymeric Prodrugs of Erlotinib for Colon Drug Delivery

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200811124013 ◽

2020 ◽

Vol 20 ◽

Author(s):

Sahil Kumar ◽

Bandna Sharma ◽

Tilak R. Bhardwaj ◽

Rajesh K. Singh

Keyword(s):

Drug Delivery ◽

Colon Cancer ◽

Drug Release ◽

Anticancer Agents ◽

Release Kinetics ◽

In Vitro Release ◽

Specific Treatment ◽

Drug Conjugates ◽

Polymer Drug Conjugates

Aims: In the present study, polymer-drug conjugates were synthesized based on azo-bond cleavage drug delivery approach for targeting erlotinib as anticancer drug specifically to the colon for the proficient treatment of colon cancer. Background: Colon cancer (CC) is the third commonly detected tumor worldwide and it make up about 10 % of all cases of cancers. Most of the chemotherapeutic drugs available for treating colon cancer are not only toxic to cancerous cells but also to the normal healthy cells. Among the various approaches to get rid of the adverse effects of anticancer agents, prodrugs are one of the most imperative approaches. Objective: The objective of the study is to chemically modify the erlotinib drug through azo-bond linkage and suitable spacer which will be finally linked to polymeric backbone to give desired polymer linked prodrug. The azo reductase enzyme present in colon is supposed to cleave the azo-bond specifically and augment the drug release at the colon. Methods: The synthesized conjugates were characterized by IR and 1H-NMR spectroscopy. The cleavage of aromatic azobond resulted in a potential colon-specific liberation of drug from conjugate studied in rat fecal contents. In vitro release profiles of polyphosphazene-linked conjugates of erlotinib have been studied at pH 1.2, pH 6.8 and pH 7.4. The stability study was designed to exhibit that free drug was released proficiently and unmodified from polyphosphazene-erlotinib conjugates having aromatic azo-bond in artificial colon conditions. Results: The synthesized conjugates were demonstrated to be stable in simulated upper gastro-intestinal tract conditions. The drug release kinetics shows that all the polymer-drug conjugates of erlotinib follow zero-order release kinetics which indicates that the drug release from the polymeric backbone is independent of its concentration. Kinetic study of conjugates with slope (n) shows the anomalous type of release with an exponent (n) > 0.89 indicating a super case II type of release. Conclusion: These studies indicate that polyphosphazene linked drug conjugates of erlotinib could be the promising candidates for the site-specific treatment of colon cancer with least detrimental side-effects.

Download Full-text

Formulation and Characterization of Glimepiride Nanoparticles for Dissolution Enhancement

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681209666190422160115 ◽

2020 ◽

Vol 10 (5) ◽

pp. 649-663

Author(s):

Reena Siwach ◽

Parijat Pandey ◽

Harish Dureja

Keyword(s):

Drug Release ◽

Dissolution Rate ◽

Oral Absorption ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Class Ii ◽

Dissolution Enhancement ◽

In Vitro Drug Release ◽

Bcs Class Ii

Background: The rate-limiting step in the oral absorption of BCS class II drugs is dissolution. Their low solubility is one of the major obstacles in the process of drug development. Dissolution rate can be increased by decreasing the particle size to the nano range, eventually leading to increased bioavailability. Objective: : In the present study, glimepiride loaded nanoparticles were prepared to enhance the dissolution rate. The aim of the work was to examine the effect of polymer-drug ratio, solvent-antisolvent ratio and speed of mixing on in vitro release of glimepiride. Methods: Glimepiride is an antidiabetic drug belonging to the BCS class II drugs. The polymeric nanoparticles were formulated according to Box-Behnken Design (BBD) using nanoprecipitation technique. The prepared nanoparticles were evaluated for in vitro drug release, loading capacity, entrapment efficiency, and percentage yield. Result: It was found that NP-8 has maximum in vitro drug release and was selected as an optimized batch. Analysis of Variance (ANOVA) was applied to the in vitro drug release to study the fitness and significance of the model. The batch NP-8 showed 70.34 ± 1.09% in vitro drug release in 0.1 N methanolic HCl and 92.02 ± 1.87% drug release in phosphate buffer pH 7.8. The release data revealed that the nanoparticles followed zero order kinetics. Conclusion: The study revealed that the incorporation of glimepiride into gelucire 50/13 resulted in enhanced dissolution rate.

Download Full-text

Development and In Vitro-In Vivo Evaluation of a Novel Sustained-Release Loxoprofen Pellet with Double Coating Layer

Pharmaceutics ◽

10.3390/pharmaceutics11060260 ◽

2019 ◽

Vol 11 (6) ◽

pp. 260 ◽

Cited By ~ 4

Author(s):

Dongwei Wan ◽

Min Zhao ◽

Jingjing Zhang ◽

Libiao Luan

Keyword(s):

Citric Acid ◽

Drug Release ◽

Sustained Release ◽

Release Rate ◽

Diffusion Rate ◽

Immediate Release ◽

Pharmacokinetic Studies ◽

Release Tablet

This study aimed to develop a novel sustained release pellet of loxoprofen sodium (LXP) by coating a dissolution-rate controlling sub-layer containing hydroxypropyl methyl cellulose (HPMC) and citric acid, and a second diffusion-rate controlling layer containing aqueous dispersion of ethyl cellulose (ADEC) on the surface of a LXP conventional pellet, and to compare its performance in vivo with an immediate release tablet (Loxinon®). A three-level, three-factor Box-Behnken design and the response surface model (RSM) were used to investigate and optimize the effects of the citric acid content in the sub-layer, the sub-layer coating level, and the outer ADEC coating level on the in vitro release profiles of LXP sustained release pellets. The pharmacokinetic studies of the optimal sustained release pellets were performed in fasted beagle dogs using an immediate release tablet as a reference. The results illustrated that both the citric acid (CA) and ADEC as the dissolution- and diffusion-rate controlling materials significantly decreased the drug release rate. The optimal formulation showed a pH-independent drug release in media at pH above 4.5 and a slightly slow release in acid medium. The pharmacokinetic studies revealed that a more stable and prolonged plasma drug concentration profile of the optimal pellets was achieved, with a relative bioavaibility of 87.16% compared with the conventional tablets. This article provided a novel concept of two-step control of the release rate of LXP, which showed a sustained release both in vitro and in vivo.

Download Full-text

Preparation, evaluation, and in vitro release of chitosan-alginate tanshinone self-microemulsifying sustained-release microcapsules

Technology and Health Care ◽

10.3233/thc-202529 ◽

2020 ◽

pp. 1-9

Author(s):

Yunhong Wang ◽

Rong Hu ◽

Yanlei Guo ◽

Weihan Qin ◽

Xiaomei Zhang ◽

...

Keyword(s):

Drug Release ◽

Sustained Release ◽

Release Rate ◽

Orthogonal Design ◽

Drug Loading ◽

In Vitro Release ◽

Core Material ◽

Evaluation Indexes ◽

Vitro Release

OBJECTIVE: In this study we explore the method to prepare tanshinone self-microemulsifying sustained-release microcapsules using tanshinone self-microemulsion as the core material, and chitosan and alginate as capsule materials. METHODS: The optimal preparation technology of chitosan-alginate tanshinone self-microemulsifying sustained-release microcapsules was determined by using the orthogonal design experiment and single-factor analysis. The drug loading and entrapment rate were used as evaluation indexes to assess the quality of the drug, and the in vitro release rate was used to evaluate the drug release performance. RESULTS: The best technology of chitosan-alginate tanshinone self-microemulsifying sustained-release microcapsules is as follows: the concentration of alginate is 1.5%, the ratio of tanshinone self-microemulsion volume to alginate volume to chitosan mass is 1:1:0.5 (ml: ml: g), and the best concentration of calcium chloride is 2.0%. To prepare the microcapsules using this technology, the drug loading will be 0.046%, the entrapment rate will be 80.23%, and the 24-hour in vitro cumulative release rate will be 97.4%. CONCLUSION: The release of the microcapsules conforms to the Higuchi equation and the first-order drug release model and has a good sustained-release performance.

Download Full-text

Cefotaxime Loaded Polycaprolactone Based Polymeric Nanoparticles with Antifouling Properties for In-Vitro Drug Release Applications

Polymers ◽

10.3390/polym13132180 ◽

2021 ◽

Vol 13 (13) ◽

pp. 2180

Author(s):

Sana Javaid ◽

Nasir M. Ahmad ◽

Azhar Mahmood ◽

Habib Nasir ◽

Mudassir Iqbal ◽

...

Keyword(s):

Drug Release ◽

Polymeric Nanoparticles ◽

In Vitro Release ◽

Bacterial Strains ◽

In Vitro Drug Release ◽

Antifouling Activity ◽

Polymeric Drug ◽

Pure Drug ◽

Average Size

The objective of the present study was to achieve the successful encapsulation of a therapeutic agent to achieve antifouling functionality regarding biomedical applications. Considering nanotechnology, drug-loaded polycaprolactone (PCL)-based nanoparticles were prepared using a nano-precipitation technique by optimizing various process parameters. The resultant nano-formulations were investigated for in vitro drug release and antifouling applications. The prepared particles were characterized in terms of surface morphology and surface properties. Optimized blank and drug-loaded nanoparticles had an average size of 200 nm and 216 nm, respectively, with associated charges of −16.8 mV and −11.2 mV. Studies of the in vitro release of drug were carried out, which showed sustained release at two different pH, 5.5 and 7.4 Antifouling activity was observed against two bacterial strains, Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. The zone of inhibition of the optimized polymeric drug-loaded nanoparticle F-25 against both strains were compared with the pure drug. The gradual pH-responsive release of antibiotics from the biodegradable polymeric nanoparticles could significantly increase the efficiency and pharmacokinetics of the drug as compared to the pure drug. The acquired data significantly noted that the resultant nano-encapsulation of antifouling functionality could be a promising candidate for topical drug delivery systems and skin applications.

Download Full-text

Comparative Analysis of Morphological and Release Profiles in Ocular Implants of Acetazolamide Prepared by Electrospinning

Pharmaceutics ◽

10.3390/pharmaceutics13020260 ◽

2021 ◽

Vol 13 (2) ◽

pp. 260

Author(s):

Mariana Morais ◽

Patrícia Coimbra ◽

Maria Eugénia Pina

Keyword(s):

Drug Release ◽

In Vitro Release ◽

Morbidity Rate ◽

Coating Film ◽

Sustained Drug Release ◽

Coated Implant ◽

Poly Ethylene ◽

Coaxial Fibers ◽

Release Profiles

The visual impairment that often leads to blindness causes a higher morbidity rate. The goal of this work is to create a novel biodegradable polymeric implant obtained from coaxial fibers containing the dispersed drug—acetazolamide—in order to achieve sustained drug release and increase patient compliance, which is of the highest importance. Firstly, during this work, uncoated implants were produced by electrospinning, and rolled in the shape of small cylinders that were composed of uniaxial and coaxial fibers with immobilized drug inside. The fibers were composed by PCL (poly ε-caprolactone) and Lutrol F127 (poly (oxyethylene-b-oxypropylene-b-oxyethylene)). The prepared implants exhibited a fast rate of drug release, which led to the preparation of new implants incorporating the same formulation but with an additional coating film prepared by solvent casting and comprising PCL and Lutrol F127 or PCL and Luwax EVA 3 ((poly (ethylene-co-vinyl acetate)). Implants were characterized and in vitro release profiles of acetazolamide were obtained in phosphate buffered saline (PBS) at 37 °C. The release profile of the acetazolamide from coated implant containing Luwax EVA 3 is considerably slower than what was observed in case of coated implants containing Lutrol F127, allowing a sustained release and an innovation relatively to other ocular drug delivery systems.

Download Full-text