Prolonged Release Characteristics Research Articles

Recent Advancements in Metallic Au- and Ag-Based Chitosan Nanocomposite Derivatives for Enhanced Anticancer Drug Delivery

The rapid advancements in nanotechnology in the field of nanomedicine have the potential to significantly enhance therapeutic strategies for cancer treatment. There is considerable promise for enhancing the efficacy of cancer therapy through the manufacture of innovative nanocomposite materials. Metallic nanoparticles have been found to enhance the release of anticancer medications that are loaded onto them, resulting in a sustained release, hence reducing the dosage required for drug administration and preventing their buildup in healthy cells. The combination of nanotechnology with biocompatible materials offers new prospects for the development of advanced therapies that exhibit enhanced selectivity, reduced adverse effects, and improved patient outcomes. Chitosan (CS), a polysaccharide possessing distinct physicochemical properties, exhibits favorable attributes for controlled drug delivery due to its biocompatibility and biodegradability. Chitosan nanocomposites exhibit heightened stability, improved biocompatibility, and prolonged release characteristics for anticancer medicines. The incorporation of gold (Au) nanoparticles into the chitosan nanocomposite results in the manifestation of photothermal characteristics, whereas the inclusion of silver (Ag) nanoparticles boosts the antibacterial capabilities of the synthesized nanocomposite. The objective of this review is to investigate the recent progress in the utilization of Ag and Au nanoparticles, or a combination thereof, within a chitosan matrix or its modified derivatives for the purpose of anticancer drug delivery. The research findings for the potential of a chitosan nanocomposite to deliver various anticancer drugs, such as doxorubicin, 5-Fluroacil, curcumin, paclitaxel, and 6-mercaptopurine, were investigated. Moreover, various modifications carried out on the chitosan matrix phase and the nanocomposite surfaces to enhance targeting selectivity, loading efficiency, and pH sensitivity were highlighted. In addition, challenges and perspectives that could motivate further research related to the applications of chitosan nanocomposites in cancer therapy were summarized.

Formulation and Evaluation of Lipid Based Nanoparticles of Etravirine

Engineered nanoparticles have the potential to revolutionize the diagnosis and treatment of many diseases like HIV/AIDS. Etravirine is one of the key components of highly active antiretroviral therapy used for the treatment of HIV-1 infections. The aim of the present study was to formulate and evaluate nanostructured lipid carriers of etravirine, intended for targeted delivery to macrophages, using solvent emulsification - evaporation technique. Estimates of drug solubility were employed for selection of solid lipids, liquid lipids and stabilizers for the preparation of NLCs. Design of experiments was used to optimize the formulation with respect to drug-lipid ratio and concentration of stabilizer in the external phase using 32 full factorial design. Particle size of the carriers and drug release characteristics were the responses which were set to suitable levels for optimization. The optimized formulation was prepared and characterized for size, poly dispersity index, zeta potential, entrapment efficiency and appearance. The nanostructured lipid carriers of etravirine were prepared using stearylamine and glyceryl monostearate as solid lipids, Capryol 90 as liquid lipid and polyvinyl pyrrolidone as stabilizer. All experimental batches showed high drug loading efficiencies nearing 99%, indicating that etravirine remained closely associated with the lipids. The nanostructured lipid carriers displayed a zeta potential of -10.1 mv and a particle size of 261.6 nm with a polydispersity index of 0.374. In vitro release of etravirine from the optimized formulation at 2 h was 9% indicative of a low burst; and 56% of the entrapped drug was released after 24 h, suggesting prolonged release characteristics. Thus, etravirine loaded lipidic nanoparticles with potential for targeting cellular reservoirs of the AIDS virus such as macrophages were successfully developed.
 Keywords: Etravirine, Nanostructured lipid carriers, full factorial design

Novel Vesicular Formulation Based on a Herbal Extract Loaded with Niosomes and Evaluation of Its Antimicrobial and Anticancer Potential

This study aimed to enhance the anticancer and antibacterial properties of Pistacia atlantica through a new parenteral formulation. The innovative approach involved loading P. atlantica fruit extract onto a novel Pluronic vesicular nano platform (Nio), analyzed using various techniques like GC-Mass, SEM, DLS, and UV-vis. The results revealed a stable, spherical Nio/Extract formulation of 103 ± 4.1 nm, possessing a high zeta potential of −30 ± 2.3 mV, with an impressive encapsulation efficiency of nearly 90 ± 3.5%. This formulation exhibited heightened cytotoxicity against BT-20 and MCF-10 cell lines compared to the extract alone, indicating its potential as a drug carrier with prolonged release characteristics. Additionally, the Nio/Extract demonstrated superior antibacterial effects against Pseudomonas aeruginosa, Staphylococcus epidermidis, and Candida albicans compared to the free extract, showcasing MIC values of 211, 147, and 187 ug/mL, respectively, versus 880, 920, and 960 ug/mL for the pathogens. These findings highlight the potential of niosomal nano-carriers housing P. atlantica extract as a viable therapeutic strategy for combating both malignancies and microbial infections.

Synthesis and characterization of pH-responsive conducting polymer/Na-alginate/gelatin based composite hydrogels for sustained release of amoxicillin drug

Composite hydrogels of Na-Alginate (Na-ALG) and Gelatin (GEL) with conducting polymers (CPs) were synthesised using poly(o-phenylenediamine) (POPD), polyaniline (PANI), poly(1-naphthylamine (PNA) and poly(vinylenedine fluoride) (PVDF). The synthesised hydrogels were characterized using FTIR, scanning electron microscopy (SEM) rheology, swelling ability and in-vitro drug release characteristics. The purpose of this investigation was to determine whether these hydrogels could be used to deliver antibiotics for extended drug release. The composite hydrogels were loaded with antibiotic drug: amoxicillin in three different concentrations and the release was studied at intestinal fluid (pH 7.4) and gastric fluid (pH 1.2). Release kinetics was found to show best fit in zero order models at both pH values and showed prolonged release characteristics. The POPD-Na-ALG/GEL showed highest release at intestinal pH of 7.4, while PVDF-Na-ALG/GEL showed highest release at gastric pH at 1.2.

Pharmacokinetic Study of Abacavir Sulphate Loaded Niosomes and Proniosomes in Rats

The plasma pharmacokinetic study of abacavir sulphate was investigated after oral administration of free abacavir sulphate solution, freshly prepared niosomal and proniosomal abacavir sulphate dispersions. The abacavir sulphate loaded niosome vesicles were prepared by the thin-film hydration method and proniosomes were prepared by the slurry method using tween 60 as surfactant cholesterol as a membrane stabilizer and dicetyl phosphate as a negative charge inducer. Maltodextrin was used as a carrier in the proniosome formulations. The formulations were evaluated for various evaluation parameters such as drug-polymer interaction, phase identification analysis and in vivo pharmacokinetic study. The comparative pharmacokinetics of free, niosome encapsulated and proniosome encapsulated abacavir sulphate was evaluated in rats at a dose of 8.57 mg/kg of abacavir sulphate. The results of niosome and proniosome encapsulated abacavir sulphate showed a significant increase in bioavailability and prolonged release characteristics. Increased half-life of 3.40 h in the case of niosomes and 4.88 h in the case of proniosomes were observed. Based on the results, it can be concluded that niosomal and proniosomal formulation could be a promising delivery system for abacavir sulphate with improved oral bioavailability and prolonged drug release profiles.

Development and Characterization of Metformin Loaded Pectin Nanoparticles for T2 Diabetes Mellitus

The present investigation was aimed to formulate and evaluate Metformin loaded pectin (PCM) nanoparticles (NPs) for sustained action for management of Type 2 Diabetes Mellitus (T2DM). The nanoparticles were formulated by ionic gelation technique. The nano-formulations were subjected for the analyses of entrapment efficiency and drug release stud for 12h. The optimized formulation examined various in vitro characterizations such as particle size, zeta potential, surface morphology and FTIR studies. The in vitro heamocomptability, protein binding stability and glucose uptake studies were performed with nanoparticles. The PCMNP-4 showed drug entrapment efficiency, 68 ± 4.2 % and demonstrated favourable in vitro prolonged release characteristics. The mean particles diameter of optimized formulation was 482.7 nm and 0.270 poly dispersity index (PI), had spherical shape and zeta potential of (+38.85 mV). In addition, the nanoparticles were reasonably stable in the presence of excess bovine serum albumin, which suggested that the nanoparticles may also be stable in the blood stream. The percentage of haemolysis induced by Metformin and placebo PCNPs were less than 5%. The results indicated that the PCMNPs are hemocompatible and therefore, safe for oral administration. The glucose uptake was increased 1.5 fold in RBCs and L6 skeleton muscle cell line compared with Metformin. Hence, the designed nanoparticle system could possibly be advantageous in terms of prolonged release, to achieve reduced dose frequency and improve patient compliance.

Suberin Fatty Acids from Outer Birch Bark: Isolation and Physical Material Characterization.

The isolation and physical material properties of suberin fatty acids (SFAs) were investigated with special reference to their potential applications as novel pharmaceutical excipients. SFAs were isolated from outer birch bark (OBB) with a new extractive hydrolysis method. The present simplified isolation process resulted in a moderate batch yield and chemical purity of SFAs, but further development is needed for establishing batch-to-batch variation. Cryogenic milling was the method of choice for the particle size reduction of SFAs powder. The cryogenically milled SFAs powder exhibited a semicrystalline structure with apparent microcrystalline domains within an amorphous fatty acids matrix. The thermogravimetric analysis (TGA) of SFAs samples showed a good thermal stability up to 200 °C, followed by a progressive weight loss, reaching a plateau at about 95% volatilization at about 470 °C. The binary blends of SFAs and microcrystalline cellulose (MCC; Avicel PH 101) in a ratio of 25:75 (w/w) displayed good powder flow and tablet compression properties. The corresponding theophylline-containing tablets showed sustained or prolonged-release characteristics. The physicochemical and bulk powder properties of SFAs isolated from OBB are auspicious in terms of potential pharmaceutical excipient applications.

Pharmacokinetic analysis of modified-release metoprolol formulations: An interspecies comparison

In the current study, we investigated the metoprolol absorption kinetics of an in-house produced oral sustained-release formulation, matrices manufactured via prilling, and two commercially available formulations, ZOK-ZID® (reservoir) and Slow-Lopresor® (matrix) in both New Zealand White rabbits and Beagle dogs, using a population pharmacokinetic analysis approach.The aim of this study was to compare the in vivo pharmacokinetic (PK) profiles of different formulations based on metoprolol, a selective adrenergic β1-receptor antagonist, in dogs and rabbits and to contrast the observed differences. To that end, metoprolol (50 to 200mg) was administered to 6 Beagle dogs and 6 New Zealand White rabbits as a single intravenous (IV) bolus injection and to 8 dogs and 6 rabbits as an oral modified release formulation. To derive pharmacokinetic parameters from the data, a non-linear mixed-effects model was developed using NONMEM® where the contribution of observations below the limit of detection (BDL, below detection limit) to the parameter estimates was taken into account in the parameter estimation procedure.In both species and for the three modified release formulations, different absorption models were tested to describe the PK of metoprolol following oral dosing. In Beagle dogs, plasma concentration-time profiles were best described using a sequential zero- and first-order absorption model. In rabbits though, the absorption phase was best described using a first-order process only.In both species, the reservoir formulation ZOK-ZID® was behaving quite similarly. In contrast, the absorption properties of both matrix formulations were rather different between species. This study indicates that the PK of the reservoir formulation is similar in both species, even after accounting for the almost completely missed absorption phase in rabbits. The insights gained further illustrate that rabbits are not very well suited to study the PK of the current matrix formulations in view of their less optimal prolonged release characteristics and the resulting fast decline in metoprolol plasma levels.

Effect of different cross-linking methods and processing parameters on drug release from hydrogel beads

The purpose of this work was to evaluate different methods of cross-linking for developing diltiazem–resin complex loaded carboxymethyl xanthan gum (CMXG) hydrogel beads to achieve highest possible drug entrapment and extended release for effective cardio-protection. The hydrogel beads were prepared by ionic cross-linking and dual cross-linking using simultaneous (SIM) and sequential (SEQ) methods. Among the three methods, SEQ method produced smaller sized beads having higher drug entrapment efficacy and prolonged release characteristics as evidenced from mean dissolution time and diffusion coefficient of drug. Keeping the concentration of ionic cross-linker constant, increase in the amount of covalent cross-linker and cross-linking time decreased the drug release. Higher release of the drug in acid solution was attributed to the higher solubility of the basic drug and higher swelling of the matrices in acid solution. Comparison of FTIR spectra, drug content and dissolution profiles indicated that the drug was stable in the beads when kept under stress condition up to 3 months. In conclusion, the sequential method was found superior for producing CMXG hydrogel beads as a prolonged release delivery device in cardiovascular diseases.

Design and In Vitro Evaluation of Solid-Lipid Nanoparticle Drug Delivery for Aceclofenac

Solid-lipid nanoparticles (SLNs) are an interesting nanoparticulate delivery system. The present work was carried out with the aim to develop a prolonged release solid-lipid nanoparticulate system for the drug using aceclofenac. Aceclofenac-loaded solid-lipid nanoparticles (ACSLNs) was prepared by hot high pressure homogenization technique. Tripalmitin was used as the lipid core. Surfactants (Poloxamer 188, Tween 80, and soya lecithin) and co-surfactant (sodium tauro glycholate) were used in the formulations. The prepared ACSLN formulations were characterized for encapsulation efficiency (EE), photon correlation spectroscopy (PCS), scanning electron microscopy (SEM), and x-ray diffraction (XRD). From these studies, mean particle diameter of the formulation prepared with combination of surfactants (Poloxmer 188 and Tween 80) was about 200 nm with spherical morphology and amorphous nature. Higher EE was obtained with SLNs prepared using combination of soya lecithin and poloxmer 188. The organization and distribution of the ingredients in the nanoparticulate system were studied by differential scanning calorimetry (DSC) and the results showed that the drug is incorporated into the solid matrix. The prepared formulations demonstrated favorable in vitro prolonged release characteristics. Experimental in vitro release data were substituted in available mathematical models to establish the release kinetics of ACSLNs and it was found to follow first-order kinetics and Higuchi diffusion mechanism. Our results suggest that these SLN formulations could constitute a promising approach for the drug delivery of aceclofenac.

In vitro characterization and invivo toxicity study of repaglinide loaded poly (methyl methacrylate) nanoparticles

With the objective to achieve prolonged drug release, especially for the treatment of diabetes mellitus, and thereby to reduce the side effects of administration of conventional dosage form, repaglinide loaded PMMA nanoparticles have been formulated. These nanoparticles have been developed by solvent evaporation method and were subjected to various studies for characterization including photon correlation spectroscopy (PCS), scanning electron microscopy (SEM) and X-ray diffraction (XRD). These studies favorably revealed that the mean particle diameter of optimized formulation was 108.3 nm and had spherical morphology with amorphous nature. Moreover, these particles were also subjected to Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) for compatibility analysis between drug and polymer. The results were positive and showed that, there were no interaction between drug and polymer. The optimized formulation demonstrated favorable in vitro prolonged release characteristics. Experimental in vitro release data were substituted with available mathematical models to establish the mechanism of release of repaglinide and was found to follow zero order, diffusion and erosion mechanisms. The in vivo toxicity study in albino rats showed no significant change in biochemical and pathological examinations. Hence, the designed system could possibly be advantageous in terms of prolonged release, to achieve reduced dose frequency and improve patient compliance of repaglinide.

A double‐blind dose‐escalating trial comparing novel mesalazine pellets with mesalazine tablets in active ulcerative colitis

Mesalazine as the treatment standard for ulcerative colitis can be applied in different galenical preparations. A novel formulation of mesalazine pellets with delayed and prolonged release characteristics was compared with conventional Eudragit L-coated tablets. Furthermore, the effect of mesalazine dose escalation on nonresponders was evaluated in both treatment groups. A total of 233 patients with mild to moderately active ulcerative colitis were randomized to receive either mesalazine (1.5 g/day in three doses) as pellets (n = 115) or tablets (n = 118) for 8 weeks. At insufficient response, the dose was increased to 3.0 g. The clinical remission rate (clinical activity index < or = 4) for pellets was 67% vs. 68% for tablets which statistically proved to be not inferior (significance level alpha = 2.5%). In patients without dose increase, the remission rate was 47% (pellets) vs. 42% (tablets). Endoscopic improvement was observed in 80% (pellets) vs. 83% (tablets), and histological improvement in 48% (pellets) vs. 52% (tablets) of patients. Mesalazine pellets are as effective as tablets in the treatment of mild to moderately active ulcerative colitis. Dose escalation to 3.0 g/day is a valid option for nonresponders to a starting dose of 1.5 g/day.

Formulation of prolonged release lipid micropellets by emulsion congealing: Optimization of ketoprofen entrapment and release

An emulsion-congealing technique was used to prepare prolonged release lipid micropellets containing ketoprofen. The lipid matrix consisted of cottonseed oil/beeswax mixture and was emulsified at 70°C into 0.1 N HCI containing Tween 60 and gelatin. The studied formulation factors were the amounts of drug, Tween 60 and gelatin, in addition to the matrix composition and rate of cooling. The optimization protocol required preliminary formulation studies (11 batches) to help choose suitable levels for formulation factors, and a central composite design (17 batches) to correlate simultaneously some of these factors to measured variables, e.g., drug entrapment, particle size and dissolution parameters. The adopted optimization strategy led to formulation of micropellets of about 1.5 mm in diameter and 25% w/w drug loading with prolonged release characteristics. The study design offers adequate prediction of micropellet characteristics and provides a basis for development of other micropellet systems.

In vitro release characteristics and long term stability of poly(ethylene oxide) hydrogel vaginal pessaries containing prostaglandin E 2

The clinical potential of prostaglandin E 2 (PGE 2) and PGE analogues in labour and abortion has not been fully realised because the products available hitherto lack long-term storage stability and current formulations do not provide the prolonged slow release which is required for this usage. These properties are achieved, however, by incorporating PGE 2 in a water swellable, polymer vaginal pessary (hydrogel) which is currently in clinical use. The formation of the device, comprising poly(ethylene oxide) cross-linked polymers, from formulations of moderate molecular weight polyethylene glycol, 1,2,6-hexane triol and pure dicyclohexylmethane-4,4'-diisocyanate and the incorporation of prostaglandins in the matrix is described. The prolonged release characteristics of the pessary have been demonstrated in vitro providing fairly constant release for the first fifty percent of the PGE 2 content dispersed in the matrix. The half life time can be controlled by the pessary thickness. Radioimmunoassay of the PGE 2 content indicated that when incorporated in the polymer pessary PGE 2 was evenly distributed and possessed long-term stability .