Sustained Release Of Ibuprofen Research Articles

Formulation and Evaluation of Sustained Release Ibuprofen Matrix Tablets Using Starch from Maize Genotypes as Polymer

Abstract Objective: Maize plants have been genetically engineered to produce genotypes with agriculturally desirable traits such as high starch content, pest resistance and increased nutritional value. Maize starch has been widely used as an excipient in pharmaceutical formulations. This study aims to produce sustained release ibuprofen tablets using starch obtained from different maize genotypes as polymers. Methods: Ibuprofen matrix tablets were prepared with the starches isolated from the maize genotypes and the unmodified plant. The mechanical properties of the tablets were evaluated using the crushing strength (CS), friability (FR) and CSFR. A 32 factorial design was applied using the time taken for 50 % (T50) and 90 % (T90) drug release as dependent variables while the polymer-drug ratio and polymer types were the independent variables. Results: The CSFR was significantly higher (p<0.05) in tablets formulated with the starches obtained from the modified cultivars. Drug release for all the formulations fitted the Higuchi model while the mechanism of release was generally by super case transport. The polymer-drug ratio and polymer type strongly interacted to increase the dissolution times (T50 and T90) and CSFR. Starches isolated from the genetically modified cultivars provided a more sustained release of ibuprofen from the tablet matrix through erosion and polymer relaxation. Conclusion: The results indicate that the genetic modification of maize can quantitatively affect the drug release modifying effects of maize starch in drug formulation.

Preparation of Defect-Related Luminescent Mesoporous Silica Nanoparticle as Potential Detectable Drug Carrier.

A defect-related luminescent mesoporous silica nanoparticle (DLMSN) with simultaneous excellent luminescence, high drug loading efficiency and release capacity was prepared upon calcination of 3-aminopropyltriethoxysilane (APTES)-functionalized mesoporous silica nanoparticle (AP-MSN) under a relatively moderate temperature. Under ultraviolet excitation at 365 nm, DLMSN exhibited intense white-blue emission with a range of 400-500 nm, which was inferred to originate from the effective carbon or nitrogen defect in the particle causing by APTES calcination. Additionally, the luminescence intensity of DLMSN was significantly affected by APTES concentration and calcination temperature during the preparation procedure. Within all the tested values, the maximum luminescence intensity was achieved when APTES concentration and calcination temperature were 0.851 mmol and 300 °C, respectively. The drug storage and release tests demonstrated that DLMSN had efficient drug storage and good pH-dependent release for ibuprofen (IBU). Interestingly, ibuprofen-loaded DLMSN (IBU@DLMSN) still exhibit an intense luminescence with an emission peak at around 410 nm under 365 nm excitation, which gradually increased with the sustained release of IBU from IBU@DLMSN. These results suggest that the as-prepared DLMSN may have potential as a detectable nanocarrier in the drug delivery field.

Hot-Melt 3D Extrusion for the Fabrication of Customizable Modified-Release Solid Dosage Forms.

In this work, modified-release solid dosage forms were fabricated by adjusting geometrical properties of solid dosage forms through hot-melt 3D extrusion (3D HME). Using a 3D printer with air pressure driving HME system, solid dosage forms containing ibuprofen (IBF), polyvinyl pyrrolidone (PVP), and polyethylene glycol (PEG) were printed by simultaneous HME and 3D deposition. Printed solid dosage forms were evaluated for their physicochemical properties, dissolution rates, and floatable behavior. Results revealed that IBF content in the solid dosage form could be individualized by adjusting the volume of solid dosage form. IBF was dispersed as amorphous state with enhanced solubility and dissolution rate in a polymer solid dosage form matrix. Due to absence of a disintegrant, sustained release of IBF from printed solid dosage forms was observed in phosphate buffer at pH 6.8. The dissolution rate of IBF was dependent on geometric properties of the solid dosage form. The dissolution rate of IBF could be modified by merging two different geometries into one solid dosage form. In this study, the 3D HME process showed high reproducibility and accuracy for preparing dosage forms. API dosage and release profile were found to be customizable by modifying or combining 3D modeling.

Localized delivery of ibuprofen via a bilayer delivery system (BiLDS) for supraspinatus tendon healing in a rat model

The high prevalence of tendon retear following rotator cuff repair motivates the development of new therapeutics to promote improved tendon healing. Controlled delivery of non-steroidal anti-inflammatory drugs to the repair site via an implanted scaffold is a promising option for modulating inflammation in the healing environment. Furthermore, biodegradable nanofibrous delivery systems offer an optimized architecture and surface area for cellular attachment, proliferation, and infiltration while releasing soluble factors to promote tendon regeneration. To this end, we developed a bilayer delivery system (BiLDS) for localized and controlled release of ibuprofen (IBP) to temporally mitigate inflammation and enhance tendon remodeling following surgical repair by promoting organized tissue formation. In vitro evaluation confirmed the delayed and sustained release of IBP from Labrafil-modified poly(lactic-co-glycolic) acid microspheres within sintered poly(ε-caprolactone) electrospun scaffolds. Biocompatibility of the BiLDS was demonstrated with primary Achilles tendon cells in vitro. Implantation of the IBP-releasing BiLDS at the repair site in a rat rotator cuff injury and repair model led to decreased expression of proinflammatory cytokine, tumor necrotic factor-α, and increased anti-inflammatory cytokine, transforming growth factor-β1. The BiLDS remained intact for mechanical reinforcement and recovered the tendon structural properties by 8 weeks. These results suggest the therapeutic potential of a novel biocompatible nanofibrous BiLDS for localized and tailored delivery of IBP to mitigate tendon inflammation and improve repair outcomes. Future studies are required to define the mechanical implications of an optimized BiLDS in a rat model beyond 8 weeks or in a larger animal model.

BILAYER TABLET TENDERED IMMEDIATE RELEASE OF PARACETAMOL AND SUSTAINED RELEASE OF IBUPROFEN FOR QUICK ONSET OF ACTION AGAINST PAIN AND FEVER

Objective: The objective of this research was to formulate bi-layer tablet which contains immediate-release layer of Paracetamol for quick onset of action and sustained release of Ibuprofen for prolonging long period.
 Materials and Methods: The following chemicals were used: Paracetamol (Combiotic Global Pvt. Ltd., India), Ibuprofen (Combiotic Global Pvt. Ltd., India), microcrystalline cellulose (MCC) (Avicel), and Polyvinylpyrrolidone (PVP) K-30 (Loba Chem). Wet granulation method was adapted to formulate the bilayer tablets. The immediate-release layer of Paracetamol was prepared using sodium starch glycolate as superdisintegrants, MCC as diluent, starch as binder. The sustained release layer of Ibuprofen was prepared using high-performance liquid chromatography E50LV and ethyl cellulose as binder along with other excipients such as MCC, PVP, and magnesium stearate by wet granulation technique.
 Result and Discussion: The release rate of Paracetamol from Formulations 1 was more than 80% at 40 min. In case of Ibuprofen, sustained-release polymers such as HPMC E50 LV were used to increase the release time.
 Conclusion: The bilayer tablets were prepared and show good release rate.

3D printing of layered mesoporous bioactive glass/sodium alginate-sodium alginate scaffolds with controllable dual-drug release behaviors

Scaffolds with controlled drug release are valuable for bone tissue engineering, but constructing the scaffolds with controllable dual-drug release behaviors is still a challenge. In this study, layered mesoporous bioactive glass/sodium alginate-sodium alginate (MBG/SA–SA) scaffolds with controllable dual-drug release behaviors were fabricated by 3D printing. The porosity and compressive strength of three-dimensional (3D) printed MBG/SA–SA scaffolds by cross-linking are about 78% and 4.2 MPa, respectively. As two model drugs, bovine serum albumin (BSA) and ibuprofen (IBU) were separately loaded in SA layer and MBG/SA layer, resulting in a relatively fast release of BSA and a sustained release of IBU. Furthermore, layered MBG/SA–SA scaffolds were able to stimulate human bone mesenchymal stem cells (hBMSCs) adhesion, proliferation and osteogenic differentiation than SA scaffolds. Hence, the 3D printed MBG/SA–SA scaffolds would be prospective for the treatment of bone defects.

Preparation of solid self-emulsifying drug delivery systems using magnesium aluminometasilicates and fluid-bed coating process

Solid lipid-based drug delivery systems combine the advantages of solid dosage forms and the solubilizing potential of lipophilic vehicles. In spite of the fact that many methods were proposed for the solidification of liquid lipid formulations, there is no data on the application of the fluid-bed coating technique to impregnate porous pellets, containing magnesium aluminometasilicates with liquid self-emulsifying formulations. Moreover, the functionality of magnesium aluminometasilicates to form porous pellets by the extrusion/spheronization process has not been studied so far.Therefore, the aim of the present work was to determine if magnesium aluminometasilicates could be incorporated into pellets in the extrusion/spheronization process and then to examine if such pellets may be used as solid cores for the conversion of liquid SEDDS into solid SEDDS (S-SEDDS) in the fluid-bed coating process. To achieve these goals, three grades of Neusilin namely SG2, US2 and NS2N were combined with MCC in three wt.% ratios i.e.: 30+70, 50+50, or 70+30. The results showed that the pellets whose matrix was composed of Neusilin SG2 had the highest porosity and the best mechanical resistance. The fluid-bed coating method was found suitable for the impregnation of the placebo pellets with liquid SEDDS, containing ibuprofen as an insoluble model drug. The amount of SEDDS adsorbed on the surface of pellets with silicates was from eight to fourteen times higher as compared to pellets without silicates. The morphology, diameter and circularity of pellets before and after the fluid-bed coating process was examined by scanning electron microscopy (SEM) and the automated particle characterization system (Morphologi G3). The pellets containing Neusilin SG2 had twice as high mechanical resistance as the pellets with Neusilin US2 or Neusilin NS2N, and they were suitable for fluid-bed processing. Dissolution studies showed that from the formulation composed of 70wt.% of Neusilin SG2 after 45min, more than 75% of ibuprofen was dissolved in water and after 30min, more than 80% of ibuprofen was dissolved in the phosphate buffer. Similar results were obtained for S-SEDDS containing 70wt.% of Neusilin US2. The sustained release of ibuprofen was found if 30wt.% of Neusilin US2, 30–50% of Neusilin SG2, or 50–70wt.% of Neusilin NS2N was incorporated into the matrix of pellets.

Mesostructured multifunctional magnetic nanocomposites for potential applications

Multifunctional nanocomposites with mesoporous silica having superparamagnetic, near-infrared (NIR) plasmon resonance, and catalytic behavior, were synthesized. These nanocomposites, with an inner magnetite core, an outer mesoporous silica shell, and a gold shell sandwiched between a thin silica layer and a thick outer silica shell, were characterized using different techniques, such as transmission electron microscopy, X-ray diffraction, fourier transform infrared spectroscopy, vibrating sample magnetometer, UV–vis spectroscopy, X-ray photoelectron spectrometry, dynamic light scattering, zeta potential, N2 adsorption/desorption, and thermal gravimetric analysis. The results indicated that the nanocomposites have high magnetization (21.4emu/g) due to the inner magnetite core, significant absorbance in the NIR region due to the gold shell, large surface area (315m2/g), and mesopores (2.1nm) in the outer silica shell. The outer mesoporous silica shell was investigated for adsorption and release of drug as well as for attaching of dye molecules, while the gold shell was investigated its catalytic behavior. These multifunctional nanocomposites show adsorption and sustained release of ibuprofen, and also have excellent catalytic behavior.

Effect of Structure and Composition on Ibuprofen Drug Delivery by Calcium Phosphate Nanocarriers

The effect of structure and composition of calcium phosphate (CaP) nanoparticles namely hydroxyapatite (HA), calcium deficient hydroxyapatite (CDHA) with Ca/P ratio ranging from 1.33 to 1.61 and tricalcium phosphate (β-TCP), on the efficiency of nanoparticles as an ideal drug carrier have been investigated. Ibuprofen, an anti-inflammatory drug was chosen for this study. The CaP nanoparticles were prepared by microwave accelerated wet chemical synthesis method and were characterized by X-ray powder diffraction, infrared spectroscopy, and electron microscopic techniques. The loading and release profiles of ibuprofen from the nanocarriers was studied using UV-Vis spectroscopy. Maximum loading of the drug was observed in β-TCP (75%) followed by CDHA of Ca/P ratio 1.5. Both samples have same Ca/P ratio but have different crystal structure. Low amount of drug loading was observed in HA and other CDHAs which have Ca/P ratio different from 1.5. Although, all the samples exhibits sustained release of ibuprofen for about 7 days, the maximum release was also shown by β-TCP (26%). Among HA and CDHAs, the amount of ibuprofen release increases with increasing Ca/P ratio. The loading and release profile of ibuprofen drug seems to be strongly related to the Ca/P ratio and structure of CaP nanocarriers.

Nanostructured hollow spheres of hydroxyapatite: preparation and potential application in drug delivery

A solvothermal method has been successfully used to prepare nanostructured hydroxyapatite (HA) hollow spheres with average diameters of about 500 nm and shell thicknesses of about 100 nm in a glycerin/water mixed solvent. Transmission electron microscopy (TEM) and field-emission scanning electron microscopy (FESEM) images show that the shells of the HA hollow spheres are actually composed of nanosheets with thicknesses of about 10 nm. By tuning the glycerin/water volume ratio, two other kinds of HA solid spheres with average diameters of about 6 or 20 μm were assembled from nanoflakes. The properties of the different kinds of spheres as drug delivery carriers were evaluated. Ibuprofen (IBU) was chosen as the model drug to load into the HA samples. The nanostructured HA samples showed a slow and sustained release of IBU. The HA hollow spheres exhibited a higher drug loading capacity and more favorable release properties than the HA solid spheres and thus are very promising for controlled drug release applications.

Mesoporous bioactive glass: ideal material for higher uptake and well sustained release of ibuprofen

Mesoporous bioactive glass (MBG) and mesoporous silica (MS) have been synthesised by evaporation induced self-assembly method. Both samples possess ordered mesoporous structure and grainy morphologies. Ibuprofen was used as model drug, and the drug loading and release process were studied in detail. The MBG shows a higher drug loading capacity (46%) than that of MS (28%) due to its high surface area and pore volume and the stronger interaction between ibuprofen and Ca2+ of MBG. The release profile investigation of both samples indicated that MBG has a longer and gentle drug release process than that of MS. It can be found that MBG has the advantages for controlled release, such as higher drug loading capacity and long release effect, which makes MBG a good candidate for drug carrier.

Sustained release of ibuprofen from polymeric micelles with a high loading capacity of ibuprofen in media simulating gastrointestinal tract fluids

Amphiphilic diblock copolymers with poly(ethylene glycol) as the hydrophilic block and a random copolymer of n-butyl methacrylate or styrene and (N,N-diethylamino)ethyl methacrylate as the hydrophobic block were prepared by atom transfer radical polymerization (ATRP). Ibuprofen, a model drug that contains a carboxylic group and hydrophobic moiety, was loaded into micelles formed from the amphiphilic diblock copolymers by a combination of ionic interaction and hydrophobic effect. The loading capacity of ibuprofen in the micelles reached 60%. Loaded ibuprofen was released in a sustained fashion into media simulating gastric fluid (pH 1.6, 2h), small intestinal fluid (pH 7.4, 4h), and colon fluid (pH 6.7, 18h). Simulating the case of oral administration at 2doses per day, loaded ibuprofen was released almost linearly against time after the second dose in media simulating human gastrointestinal tract fluids.

Preparation and release study of ibuprofen‐loaded porous matrices of a biodegradable poly(ester amide) derived from L‐alanine units

AbstractScaffolds of a biodegradable poly(ester amide) constituted of L‐alanine, sebacic acid, and 1,12‐dodecanediol units (abbreviated as PADAS) were prepared by the compression‐molding/particulate‐leaching method. The influence of the type, size, and percentage of salt on the scaffold porosity and morphology was evaluated. The thermal behavior and crystallinity were also studied for samples obtained under different processing conditions. PADAS scaffolds were not cytotoxic because they showed good cell viability and supported cell growth at a similar ratio to that observed for the biocompatible materials used as a reference. The use of PADAS scaffolds as a drug‐delivery system was also evaluated by the employment of ibuprofen, a drug with well known anti‐inflammatory effects. Different drug‐loading methods were considered, and their influence on the release in a Sörensen's medium was evaluated as well as the influence of the scaffold morphology. A sustained release of ibuprofen could be attained without the production of a negative effect on the cell viability. The release kinetics of samples loaded before melt processing was well described by the combined Higuchi/first‐order model. This allowed the estimation of the diffusion coefficients, which ranged between 3 × 10−14 and 5 × 10−13 m2/s. Samples loaded by immersion in ibuprofen solutions showed a rapid release that could be delayed by the addition of polycaprolactone to the immersion medium (i.e., the release rate decreased from 0.027 to 0.015 h−1). © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.

Studies on the release of ibuprofen from Al3+ ion cross‐linked homopolymeric and interpenetrating network hydrogel beads of carboxymethyl xanthan and sodium alginate

AbstractHomopolymeric and interpenetrating network (IPN) hydrogel beads of ibuprofen (IBP), a nonsteroidal anti‐inflammatory drug, were prepared using carboxymethyl xanthan and sodium alginate as polymers and AlCl3 as a cross‐linking agent. Formation of IPN structure was examined using FTIR analysis. The effect of composition of the hydrogel beads and the amount drug load on the release of IBP was studied in acidic and phosphate buffer (PB) solution of pH 6.8. In accordance with the swelling behavior of the beads, drug release from the IPN beads in acidic solution was found to be confined within those from homopolymeric beads. On the other hand, drug release from IPN beads in PB solution was found to be less than those from the homopolymeric beads although the swelling of the beads followed the same trend as in an acidic solution. An increase in the drug load further decreased the drug release from all the beads in both the dissolution media. FTIR, XRD, and DSC analyses demonstrated the absence of any interaction between the drug and the polymers. The results indicated that IPN hydrogel beads provided more sustained release of IBP than homopolymeric beads. © 2011 Wiley Periodicals, Inc. Adv Polym Techn 30:1–11, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/adv.20199

Controlled release properties and final macroporosity of a pectin microspheres–calcium phosphate composite bone cement

The use of calcium phosphate cements (CPC) is restricted by their lack of macroporosity and poor drug release properties. To overcome these two limitations, incorporating degradable polymer microparticles into CPC is an attractive option, as polymer microparticles could help to control drug release and induce macroporosity after degradation. Although few authors have yet tested synthetic polymers, the potentiality of polysaccharides’ assuming this role has never been explored. Low-methoxy amidated pectins (LMAP) constitute valuable candidates because of their biocompatibility and ionic and pH sensitivity. In this study, the potentiality of a LMAP with a degree of esterification (DE) of 30 and a degree of amidation (DA) of 19 was explored. The aim of this study was to explore the influence of LMAP microspheres within the composite on the cement properties, drug release ability and final macroporosity after microspheres degradation. Three LMAP incorporation ratios, 2%, 4% and 6% w/w were tested, and ibuprofen was chosen as the model drug. In comparison with the CPC reference, the resulting composites presented reduced setting times and lowered the mechanical properties, which remained acceptable for an implantation in moderate-stress-bearing locations. Sustained release of ibuprofen was obtained on at least 45 days, and release rates were found to be controlled by the LMAP ratio, which modulated drug diffusion. After 4 months of degradation study, the resulting CPC appeared macroporous, with a maximum macroporosity of nearly 30% for the highest LMAP incorporation ratio, and interconnectivity between pores could be observed. In conclusion, LMAP appear as interesting candidates to generate macroporous bone cements with tailored release properties and macroporosity by adjusting the pectin content within the composites.

Sustained Release of Ibuprofen from Polyelectrolyte Encapsulated Mesoporous Carriers

Polyelectrolyte multilayers are receiving much attention due to their insolubility and due to structural responses induced in them by changes in solution properties such as, for example, temperature, pH or ionic strength. These characteristics make polyelectrolyte multilayers highly interesting in encapsulation technology and controlled delivery applications. However, producing dry, biocompatible formulations for storage of low molecular weight substances poses a challenge. One possibility is to make use of a well-defined mesoporous inorganic carrier material as host for the model substance (in our case ibuprofen). Control over release properties are enabled by polyelectrolyte encapsulation of the inorganic carrier. We built such multilayers through consecutive deposition of PAH and PSS on top of a first layer ofr PEI. These layers were adsorbed either in presence or absent of ibuprofen. The influence of long time storage, 2 years, of the samples was also investigated. The polyelectrolyte multilayer structure was investigated in detail by Dual Polarization Interferometry (DPI), and we use these data to interpret the measured release profiles.

4867987 Pharmaceutical product for the sustained release of ibuprofen

4867987 Pharmaceutical product for the sustained release of ibuprofen