Release Of Nifedipine Research Articles

Application of halloysite clay nanotubes as a pharmaceutical excipient

Halloysite nanotubes, a biocompatible nanomaterial of 50–60nm diameter and ca. 15nm lumen, can be used for loading, storage and sustained release of drugs either in its pristine form or with additional polymer complexation for extended release time. This study reports the development composite tablets based on 50wt.% of the drug loaded halloysite mixed with 45wt.% of microcrystalline cellulose. Powder flow and compressibility properties of halloysite (angle of repose, Carr’s index, Hausner ratio, Brittle Fracture Index, tensile strength) indicate that halloysite is an excellent tablet excipient. Halloysite tubes can also be filled with nifedipine with ca. 6wt.% loading efficiency and sustained release from the nanotubes. Tablets prepared with drug loaded halloysite allowed for almost zero order nifedipine release for up to 20h. Nifedipine trapped in the nanotubes also protect the drug against light and significantly increased the photostability of the drug. All of these demonstrate that halloysite has the potential to be an excellent pharmaceutical excipient that is also an inexpensive, natural and abundantly available material.

Poly( N ‐isopropylacrylamide)/polyurethane core–sheath nanofibres by coaxial electrospinning for drug controlled release

A new type of drug carrier with thermo-sensitivity is reported. The system consisted of poly(N-isopropylacrylamide) (PNIPAAm) and polyurethane (PU) and two kinds of polymer were spun into core–sheath nanofibres without bead defects by coaxial electrospinning technique. Poor soluble nifedipine was used as a model drug to evaluate the release behaviour of drug from nanofibre carriers. Results showed that the diameter and diameter distribution of nanofibres varied with the ratios of the outer flow rate to the inner flow rate. PNIPAAm/PU core–sheath electrospun nanofibres maintained the thermo-sensitivity of PNIPAAm and the wettability of the electrospun nanofibres could be adjusted effectively by the change of the temperature. In-vitro release of nifedipine from nanofibre carriers showed that core–sheath electrospun nanofibres as the drug carrier could slow down the release rate of nifedipine compared with that of PNIPAAm/PU composite electrospun nanofibres, and then could effectively achieve the controlled release of nifedipine, avoiding the concentrated release of drug and reduce the toxicity.

PLA/CS/Nifedipine Nanocomposite Films: Properties and the In Vitro Release of Nifedipine

The polylactic acid (PLA)/chitosan (CS) films containing a drug, nifedipine (NIF), in the presence of polyethylene oxide (PEO) as a compatibilizer were prepared by the solution method. This method has not been used to form films containing four components (PLA, CS, NIF, PEO) up to now. The CS, PEO, and NIF contents are 25 wt.%, 6–8 wt.%, and 10–50 wt.% in comparison with PLA weight, respectively. Fourier transform infrared spectroscopy (FTIR), thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC), and field emission scanning electron microscopy (FESEM) were used to characterize the interactions, properties, and morphology of the PLA/CS/PEO/NIF films. The FTIR, TGA, and DSC results show that NIF carried by PLA/CS/PEO films and PLA, CS, NIF had better interaction and were more compatible when using PEO. The surface morphology of PLA/CS/PEO/NIF films was similar to that of PLA/CS/PEO films. Moreover, this was the first time drug loading and NIF release content from PLA/CS/PEO films were determined by the ultraviolet–visible (UV–Vis) spectroscopy method. The drug loading of PLA/CS/PEO/NIF films was from 80.99% to 93.61%. The in vitro NIF release studies were carried out in pH 2, 6.8, and 7.4 solutions corresponding to the pH of stomach, colon, and duodenum regions in the human body, respectively. The NIF release content in different pH solutions is in the order: pH 2 > pH 6.8 > pH 7.4 and increases when there is increasing NIF loading. The PLA/CS/PEO films are potential materials to apply for long-circulating systems for NIF delivery.

In vitronifedipine release from poly(lactic acid)/chitosan nanoparticles loaded with nifedipine

ABSTRACTIn this study, nanoparticles based on poly(lactic acid) (PLA), chitosan (CS), and nifedipine (NIF) were prepared by an emulsion method with poly(ethylene oxide) (PEO) as an emulsifier. We investigated the most suitable conditions for preparing the poly(lactic acid)/chitosan/nifedipine nanoparticles (PCNs) by changing the distilled water volume, PEO content, and PLA/CS ratio. NIFs with different contents were loaded into poly(lactic acid)/chitosan nanoparticles (PCs) to studyin vitrodrug‐delivery systems. The PCNs were characterized with a Zetasizer particle size analyzer, field emission scanning electron microscopy, Fourier transform infrared (FTIR) spectroscopy, and X‐ray diffraction (XRD) methods. From the obtained results of the particle size parameters of the PCNs, the most suitable conditions for the preparation of the PCNs were found. The FTIR spectroscopy and XRD results show that NIF was loaded into the PCs. The PCNs had major basic particle sizes in the range 20–40 nm. NIF release from the PCNs was studied as a function of the pH of the immersed solution, the immersion time, and the NIF content. The kinetics of drug release were investigated and are reported to determine the type of release mechanism. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2016,133, 43330.

Fast production of high-methoxyl pectin aerogels for enhancing the bioavailability of low-soluble drugs

Aerogels are outstanding materials with high porosities, low densities and large surface areas. Moreover, polysaccharide aerogels e.g. pectin aerogels, are gaining interest due to their biodegradability and biocompatibility, which makes them interesting materials for medical, pharmaceutical or food applications. In this research we propose a new method for the gelation of high-methoxyl pectin. In later continuation those aerogels will be proposed as carriers to enhance the dissolution of poorly soluble drugs. Nifedipine was used as model drug. The aim of the research was to investigate two methods for the drug loading; first by adding the drug during the sol–gel process and second by supercritical adsorption. By the novel gelation method, the overall aerogel production time was shorter. In addition, prepared aerogels possessed highest yet reported surface area for high-methoxyl pectin monolithic aerogels, namely around 390m2g−1. Drug loading during the sol–gel process was higher (22%), however also supercritical adsorption gave comparably good results (13%) according to the low solubility of nifedipine. Nifedipine release was controlled over 12h and 100% (60mg) drug release was achieved in this period.

Novel pH-sensitive blend microspheres for controlled release of nifedipine – An antihypertensive drug

Water-soluble acrylamide (AAm)-grafted-chitosan (CS) copolymer (AAm-g-CS) was synthesized using potassium persulfate (PPS) initiator from which interpenetrating polymer network (IPN) microspheres were prepared by water-in-oil (w/o) emulsion that are cross-linked with glutaraldehyde (GA) and used for encapsulating nifedipine (NFD). Microspheres were coated with sodium alginate (NaAlg) to enhance their pH-sensitivity for extending the release time of NFD up to 14h, releasing with 93% of NFD. The coated and uncoated microspheres were characterized by Fourier transform infrared spectra (FTIR) and differential scanning calorimetry (DSC) to understand chemical interactions and blend compatibility. Morphology and particle size of the microspheres were assessed by scanning electron microscopy (SEM) and particle zeta analyzer, respectively. Swelling and in vitro release experiments were performed in pH 1.2 and 7.4 buffer media, which showed a dependence on IPN blend composition, extent of cross-linking and amount of AAm used. Empirical analysis of drug patterns suggested the differences between NaAlg coated and uncoated microspheres.

Development of Sustained-Release Microbeads of Nifedipine and <i>In vitro</i> Characterization

Purpose: To formulate and evaluate sustained-release microbeads of nifedipine for prolonged delivery. Methods: Nifedipine microbeads were prepared using sodium alginate and pectin in different ratios by ionic-gelation method. The microbeads were evaluated for surface morphology and shape by scanning electron microscopy (SEM), micromeritic properties, microencapsulation efficiency and in vitro drug release. The microbeads were also assessed by Fourier Transform Infra-red Spectroscopy (FTIR) and differential scanning calorimetry (DSC) to determine drug-polymer interaction, if any. Results: FTIR and DSC results indicate absence of interaction between the drug and polymers used. Good rheological behavior was demonstrated with an angle of repose < 30o, and Carr’s index and Hausner’s ratio of < 10% and < 1.12, respectively Microbead size, yield and entrapment efficiency were in the range of 695 to 733 um, 69 to 75% and 54 to 63%, respectively. SEM revealed that the microbeads were discrete, largely spherical and free-flowing. Higuchi model was the best fit for the dissolution data and followed non-Fickian diffusion mechanism. Conclusion: The microbead formulation would be suitable for sustained release of nifedipine.

Development and characterization of ethylcellulose based microsphere for sustained release of nifedipine

This article introduced the work of ethylcellulose based polymeric microsphere loaded with nifedipine for reduction in frequency of administration with low solubility in aqueous medium and high rate of absorption in the stomach. The non-aqueous polymeric suspension was put dropwise into an aqueous medium containing polyvinyl alcohol as a surfactant for the synthesis of microsphere by solvent evaporation. The microspheres were characterized by different techniques, namely, XRD, SEM, and NMR. The formation of microspheres was confirmed by SEM. XRD analysis revealed the semi-crystallinity nature of microspheres. The NMR study indicated the presence of hetero-aromatic nucleus in the microsphere.

Preparation and pharmaceutical evaluation of nano-fiber matrix supported drug delivery system using the solvent-based electrospinning method

In this study, utilizing the solvent-based electrospinning (ES) method, which is mainly employed in the textile industry, we prepared nanofiber-based capsules including drugs for controlled-release delivery systems using methacrylic acid copolymer (EUDRAGIT(®) S100, MAC) as a polymer, and evaluated their in vitro drug dissolution profiles and in vivo pharmacokinetics in rats. As the model drugs, uranine (UN) was used as a water-soluble drug and nifedipine (NP) as a water-insoluble drug. The mean diameters of drug free nano-fiber and nano-fiber including NP or UN were 751.5 ± 67.2, 703.3 ± 71.2 and 2477.8 ± 206.1 nm, respectively. X-ray diffraction for the nano-fibrotic sheet showed that UN and/or NP were packed in nano-fiber in an amorphous form. The in vitro release of UN or NP from the nano-fiber packed capsules (NFPC) and milled-powder of nano-fiber packed capsules (MPPC) showed controlled release of UN or NP as compared to capsules of a physical mixture of MAC and each drug. An in vivo pharmacokinetic study in rats after intraduodenal administration of NFPC or MPPC including UN and/or NP clearly demonstrated that application of nano-fibrotic technique as a drug delivery system offers drastic changes in pharmacokinetic profiles for both water-soluble and water-insoluble drugs. The ES method is a useful technique to prepare a nano-fiber like solid dispersion for polar or nonpolar drugs, and has wide potential pharmaceutical applications.

The influence excipients on the dissolution profiles of nifedipine tablets

PURPOSE: Study of dissolution profiles of nifedipine tablets from different manufacturers to further assess of their equivalence in vitro, as well as study of the dependence of the dissolution profile on the adjuvants composition. MATERIAL AND METHODS: 3 buffer media with pH 1.2 (hydrochloric acid buffer); 4.5 (acetate buffer); 6.8 (phosphate buffer) was used. The absorptions were observed at 343. RESULTS: The dissolution profiles of nifedipine tablets from different manufacturers have been studied and have been founded that the percentage of nifedipine release from the sample B is higher than from “Corinfar”, and the percentage of nifedipine release from “Corinfar” is higher than from the sample A. Adjuvants composition of nifedipine tablets have been studied. It is founded that the inclusion of surfactants, solubilizers and emulsifiers into tablets contribute to increasing of active substance release from the dosage form. CONCLUSIONS: Found that the introduction of surfactants into tablets, solubilizers and emulsifiers help to increase the release of active substance from the dosage form.

Sustained-release pellets of nifedipine using microcrystals combined with MCC-based matrix

The purpose of this study was to prepare sustained-release pellets of nifedipine (NSPs) based on MCC matrix. Wet-milling and extrusion-spheronization techniques were employed to prepare the microcrystals and pellets, respectively. The drug release mechanism and the influencing factors were investigated. After milled with HPMC (E5), the mean particle size of nifedipine in co-grinding mixture (CGM) was 5 μm, which is 15-fold smaller than that of raw material. DSC, X-ray powder diffraction and microscopic observation confirmed the microcrystals of drug were maintained in the CGM. With increased milling time and the content of HPMC, the dissolution rate was greatly enhanced compared with the raw material. The NSPs prepared by MCC and the CGM, which was obtained by cogrinding nifedipine with 5% HPMC solution for 210 min, exhibited sustained release pattern within 8 h. Nifedipine release from MCC-based NSPs followed the Korsmeyer model and closely related to the microstructure of pellet. High stability of NSPs was confirmed after 6 months of accelerated stability test. Using commercially available sustained product as reference, bioequivalence study in beagle dogs was executed and two formulations were bioequivalent. This sustained release pellet formulation of nifedipine was advantageous with convenient and easy scaled-up preparation process.

Binary Blend of Glyceryl Monooleate and Glyceryl Monostearate for Magnetically Induced Thermo-Responsive Local Drug Delivery System

To develop a novel monoglycerides-based thermal-sensitive drug delivery system, specifically for local intracavitary chemotherapy. Lipid matrices containing mixtures of glyceryl monooleate (GMO) and glyceryl monostearate (GMS) were evaluated for their potential application as magnetically induced thermo-responsive local drug delivery systems using a poorly water-soluble model drug, nifedipine (NF). Oleic acid-modified iron oxide (OA-Fe3O4) nanoparticles were embedded into the GMO-GMS matrix for remote activation of the drug release using an alternating magnetic field (AMF). The crystallization behavior of binary blends of GMO and GMS as characterized by DSC did show temperature dependent phase transition. GMO-GMS (75:25wt%) blend showed a melting (T m ) and crystallization (T c ) points at 42°C and 37°C, respectively indicating the potential of the matrix to act as an 'on-demand' drug release. The matrix released only 35% of the loaded drug slowly in 10days at 37°C whereas 96% release was obtained at 42°C. A concentration of 0.5% OA-Fe3O4 heated the matrix to 42.3 and 45.5°C within 5min and 10min of AMF exposure, respectively. The in vitro NF release profiles form the monoglycerides matrix containing 0.5% OA-Fe3O4 nanoparticles after AMF activation confirmed the thermo-responsive nature of the matrix that could provide pulsatile drug release 'on-demand'.

Novel blend microspheres of poly(vinyl alcohol) and succinyl chitosan for controlled release of nifedipine

Water-soluble succinyl chitosan (SCS) was synthesized by reacting succinic anhydride with –OH and –NH2 reactive groups of chitosan (CS). The blend hydrogel microspheres were prepared from SCS with poly(vinyl alcohol) (PVA) by water-in-oil (w/o) emulsion cross-linking using glutaraldehyde (GA) as the cross-linking agent. Nifedipine (NFD), an antihypertensive drug having a plasma half-life of 2 h, was encapsulated giving encapsulation efficiency up to 92 % and its release was extended up to 12 h. Scanning electron microscopy (SEM) confirmed the spherical nature and smooth surfaces of the microspheres, while Fourier transform infrared spectroscopy (FTIR) confirmed succinylation of CS and chemical stability of NFD in the matrix. Thermogravimetry (TGA) and differential scanning calorimetry (DSC) characterized the SCS and the blend hydrogel microspheres. X-ray diffraction (XRD) and DSC were also used to study the crystalline or amorphous nature of NFD. Swelling and in vitro release experiments performed in pH 1.2 and 7.4 buffer media showed a dependence of blend composition, extent of cross-linking and pH of the media. The mechanism of drug release as analyzed by an empirical equation, suggested non-Fickian trends.

Tab-in-tab formulation of ramipril and nifedipine for effective anti-hypertensive activity

BackgroundThe aims of this work were to enhance the solubility of nifedipine in acidic medium; to formulate and characterize tab-in-tab dosage form for immediate release of nifedipine and controlled release of ramipril and to avoid the mutual interactions of drugs. This combination appreciably intended to reduce the incidence of peripheral edema and reflex tachycardia. MethodsRamipril was firstly wet granulated with a HPMC polymer to form stable granules and then was directly compressed to form a core tablet. Enteric coating was given with a water insoluble polymer to withstand the acidic pH of stomach. Initially, nifedipine microcapsules were prepared, granulated with excipients and then compressed, keeping the inner tablet in between the granules. Results and discussionThis novel tab-in-tab dosage form allowed the nifedipine to release for stomach-specific absorption and ramipril to the intestine-specific absorption. Distinctive release profiles were obtained for immediate- and controlled-release tab-in-tab formulations, giving better bioavailability with no metabolic side-effects. ConclusionTab-in-tab drug delivery system used to formulate combination drugs with different pharmacokinetic profiles provide reduction in dosage, dosing frequency, reduction in side effects, additive effects and single pill convenience.

Formulation and pharmacokinetic evaluation of once-daily sustained-released system of nifedipine with solid dispersion and coating techniques

A novel sustained-release system was developed for poorly water-soluble drugs by applying solid dispersion (SD) technique to improve the solubility. The SD systems composed of polyvinyl pyrrolidone and stearic acid could not control the release of nifedipine. When the above SD granules were coated with ethylcellolulose (EC10, 45 and 100cp), the dissolution rate extended from 16 to 20 h. When the concentration of EC100cp was increased to 4-6 %, the sustained-release formulation F7 and F8 prepared with 4 % EC100cp and 6 % EC100cp, respectively, could control the drug release in a better manner, namely, they could control drug release in the initial hours with a high cumulative amount of drug at 24 h. The mechanism of drug release from F7 and F8 was diffusion coupled with erosion. When immediate-release capsules was orally administered to rabbits, its absorption was very rapid with a short elimination half-life, while a prolonged maintenance of the plasma drug level up to 24 h was obtained for F7 and F8. Furthermore, the oral bioavailability of F7 and F8 was significantly improved. The results suggested that this novel sustained-release system would be a promising system to improve the solubility and sustain the absorption of poorly water-soluble drugs.

Electrospun poly(N-isopropylacrylamide)/poly(caprolactone)-based polyurethane nanofibers as drug carriers and temperature-controlled release

Electrospun micro- and nanofibers are being increasingly investigated for drug delivery. The components and stimuli-responsive properties of the fibers are important factors influencing the drug release behavior. The aim of this study was to fabricate thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm)/polyurethane (PU) nanofibers using a single-spinneret electrospinning technique. The electrospun nanofibers were used as drug carriers by co-spinning with nifedipine (NIF) and the release behavior of NIF can be controlled by the response of the nanofibers to temperature. The morphologies of the nanofibers and the composites with NIF were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The interactions between PNIPAAm and PU and the existence of the water-insoluble drug NIF were introduced and confirmed by Fourier-transform infrared spectroscopy (FTIR). The thermo-responsive behavior of the nanofibers was detected by contact angle (CA) measurements. Mechanical properties were analyzed by tensile test and the release behavior of NIF from the PNIPAAm/PU nanofibers was observed by SEM and demonstrated by UV-vis spectroscopy. It was found that uniform fibers of NIF and PNIPAAm/PU could be fabricated without the appearance of particles on the surface. The release of NIF from the nanofibers could be controlled effectively by adjusting the temperature of the environment surrounding the thermo-responsive nanofibers.

Controllable drug release of electrospun thermoresponsive poly(N‐isopropylacrylamide)/poly(2‐acrylamido‐2‐ methylpropanesulfonic acid) nanofibers

Electrospinning micro- and nanofibers are being increasingly investigated for drug delivery. The components and their stimuli-responsive properties of fibers are important factors influencing the drug release behavior. The aim of this study is to fabricate thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm)/poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) nanofibers by single-spinneret electrospinning technique. The electrospun nanofibers are used as a drug carrier by cospinning with nifedipine (NIF), and the release behaviors of NIF from the thermoresponsive nanofibers can be controlled by the response of nanofibers with temperature. The morphology of the nanofibers and its composites with NIF was determined by scanning electron microscopy (SEM). The hydrogen bond interactions between PNIPAAm/PAMPS and the water-insoluble drug of NIF were introduced and confirmed by Fourier-transform infrared spectroscopy and energy dispersive spectrometer. The thermoresponsive properties of nanofibers were investigated by contact angle (CA) measurements. The release behaviors of NIF from the PNIPAAm/PAMPS nanofibers were observed by SEM and demonstrated by UV-vis spectroscopy. It was found that uniform fibers of NIF and PNIPAAm/PAMPS could be fabricated without particles on the surface. The release of NIF from nanofibers could be controlled effectively by the changes of hydrogen bonds between PNIPAAm/PAMPS and NIF, and by adjusting temperatures of the thermoresponsive nanofibers.

Biopolymeric nifedipine powder for acceleration of wound healing

Nine biodegradable polymeric powders of chitosan; with or without gelatin; containing nifedipine (NF), were prepared via spray drying for acceleration of wound healing. The angle of repose of powders ranged from 30° to 40° for F 3 and chitosan/gelatin (C 2), respectively. Upon spray drying, the mean particle size (PS) of chitosan was greatly reduced from 294 to 3.4 μm, while all formulae showed a PS near 3 μm. Specific surface area of the powders ranged from 0.06 × 10 5 to 2.03 × 10 5 cm 2 g. Powders exposure to glutraldehyde (GA) vapors gave smaller particles with higher densities with F 4 showing a mean PS of 0.4 μm. NF dissolution pattern in PBS, was highest from F 2 with 33% released after 30 min while F 3 showed only 4.5% NF released after the same period. Exposure to GA showed a reduction in NF release especially with F 5 showing 30% release after 3 h. Tensile strength of 12 days-post incision wound in rats showed a maximum value of 4.7 kg cm −2 for F 3 compared with 3.3 kg cm −2 for the control. Excision wounds treated with F 3 also showed a fully developed epithelium with normal keratinization, and an average wound contraction of 99% compared with 79.5% for the control.

Effects of pH‐Sensitive Groups on Poly(ethylene oxide)‐block‐poly(ϵ‐caprolactone) Block Copolymer Micelles Used as Drug Carriers

AbstractA new type of drug delivery system consisting of an amphiphilic polymer micelle with pH‐sensitive groups is reported. The polymer comprises mPEG [poly(ethylene glycol) monomethyl ether], PCL [poly(ϵ‐caprolactone)], and either PAA [poly(acrylic acid)] or PMAA [poly(methacrylic acid)]. Both mPEG‐b‐PCL and mPEG‐b‐PCL‐b‐PAA/PMAA are characterized by 1H NMR, FTIR, and gel permeation chromatography (GPC). The diameters of the mPEG‐b‐PCL‐b‐PAA/PMAA micelles are found to increase with increases in pH and studies show that in vitro release of nifedipine from mPEG‐b‐PCL‐b‐PAA/PMAA micelles becomes faster as the pH value of phosphate‐buffered saline (PBS) increases. This new type of pH‐sensitive polymeric micelle can potentially be used as a drug carrier for oral administration of water‐insoluble drugs.

PH responsive itaconic acid grafted alginate microspheres for the controlled release of nifedipine

A series of pH responsive alginate-g-poly(itaconic acid) (NaAlg-g-PIA) microspheres were prepared as drug delivery matrices of nifedipine cross-linked by glutaraldehyde (GA) in the hydrochloric acid catalyst. Graft copolymers of sodium alginate with itaconic acid were synthesized using ceric ammonium nitrate. The chemical stability of the nifedipine after encapsulation into microspheres was confirmed by FTIR, DSC and X-RD analysis. The preparation conditions of the NaAlg-g-PIA microspheres such as graft yield, GA concentration, exposure time to GA and drug amount were optimized by considering the percentage entrapment efficiency, particle size, swelling capacity and their release data. The results showed that NaAlg-g-PIA microspheres are pH responsive. The release of nifedipine from grafted microspheres was slower for the pH 1.2 solution than that of the pH 7.4 buffer solution. It has been observed that an increase in exposure time, drug amount, GA and NaAlg-g-PIA concentrations causes a decrease in the nifedipine release from the microspheres, whereas an increase in graft yield leads to an increase in the nifedipine release.