Significant Increase In Drug Release Research Articles

A dual pH- and temperature-responsive hydrogel produced in situ crosslinking of cyclodextrin-cellulose for wound healing

Cellulose hydrogels have gained attention in the field of wound healing due to their biodegradability, biocompatibility, and the capacity to sustain a humid environment that promotes healing. Conventional cellulose hydrogels were usually lacked responsiveness to changing wound conditions, and limited capacity for controlled release of active substances. The composite hydrogels with Berberine (BBR) loading were prepared from bamboo parenchymal cellulose and in situ crosslinking carboxylated-β-cyclodextrin (BPCH-B) via dissolution. The inclusion of BBR enhanced the antibacterial properties of cellulose hydrogel while maintaining biocompatibility and drug delivery capabilities. The dual-responsive dressing was demonstrated to modulate drug release kinetics in accordance with the pH and temperature conditions prevailing within the wound site. Specifically, study exhibited a significant increase in drug release (over 70 %) under alkaline pH (7.6) and temperature (40 °C) conditions. Full-thickness wound healing experiments indicated that BPCH-B had better healing ability, and the wound healing area of BPCH-B treated was 80 % within 12 days, while the control group was only 50 %. This strategy for generating functional wound healing can be further control release of drug compounds for treatment of wounds, enabling development of practical wound care materials.

Evaluation of Drug Release Profiles of Titanium Plates Coated with PLGA or Chitosan with Meropenem Using UPLC: An In Vitro Study

In some cases, titanium plates could be a reservoir for harboring bacteria resulting in challenging cases of infection. Current estimates indicate that 10–12% of plates require removal due to infection, exposure, pain, and discomfort. The present investigation was conducted to evaluate the potential sustained meropenem-coated plates amalgamated with “PLGA” polylactic co-glycolic acid and chitosan polymers with the concurrent sterilization effect of gamma irradiation. After coating the plates with either M “meropenem”, MP “meropenem-PLGA, or MC “meropenem-chitosan”, they were divided into two groups of sterile and non-sterile coated plates. The drug release was studied over three-time intervals of 1, 3, and 7 days using ultrahigh-performance liquid chromatography. Overall, the three materials had similar drug release on day one, both in sterile and non-sterile groups, while on days 3 and 7, a noticeable increase in the drug release was perceived in favor of MP. At the same time, no statistically significant difference was observed between sterile and non-sterile groups. A statistically significant increase in drug release was observed between and within the materials over time, with no overall difference between sterile and non-sterile groups.

FORMULATION AND OPTIMIZATION OF RITONAVIR NASAL NANOSUSPENSION FOR BRAIN TARGETING

Nowadays, HIV associated neurological disorder especially HIV-1 virus infection is enhanced. Current available HIV therapies only reduce the plasma viral level and do not kill the virus completely. Administered dosage form does not reach the central nervous system (CNS) completely by the conventional approach. The oral route of drug administration,causes gastrointestinal irritation, hepatic metabolism and slow onset of action and some methods are invasive, resulting in the patient's non compliance. To overcome these problems, an effective novel formulation that will directly reach the CNS or brain needs to be developed.This study aims to formulate intranasal nanosuspension of ritonavir. Ritonavir is widely used as an antiretroviral agent and it is a protease enzyme inhibitor which is poorly soluble in water. High pressure homogenization technique was used for preparation prepare and optimization of nanosuspension by using 2 factors 3 level full factorial design, which is further characterized for particle size, polydispersity index, zeta potential, pH, drug content, in vitro drug diffusion and ex vivo permeation study. For stability of nanosuspension, lyophilization of optimized formulation was done. A comparison study between plain drug, nanosuspension and the lyophilized formulation was carried out, and it showed a significant increase in drug release from the membrane.

Magnetic tri-bead microrobot assisted near-infrared triggered combined photothermal and chemotherapy of cancer cells

Magnetic micro/nanorobots attracted much attention in biomedical fields because of their precise movement, manipulation, and targeting abilities. However, there is a lack of research on intelligent micro/nanorobots with stimuli-responsive drug delivery mechanisms for cancer therapy. To address this issue, we developed a type of strong covalently bound tri-bead drug delivery microrobots with NIR photothermal response azobenzene molecules attached to their carboxylic surface groups. The tri-bead microrobots are magnetic and showed good cytocompatibility even when their concentration is up to 200 µg/mL. In vitro photothermal experiments demonstrated fast NIR-responsive photothermal property; the microrobots were heated to 50 °C in 4 min, which triggered a significant increase in drug release. Motion control of the microrobots inside a microchannel demonstrated the feasibility of targeted therapy on tumor cells. Finally, experiments with lung cancer cells demonstrated the effectiveness of targeted chemo-photothermal therapy and were validated by cell viability assays. These results indicated that tri-bead microrobots have excellent potential for targeted chemo-photothermal therapy for lung cancer cell treatment.

Formulation and Taste Masking of Metronidazole Oral Disintegrating Tablets by a Novel Approach

The anti-protozoal drug, metronidazole, is developed as an oral disintegrating tablet (ODT) to treat amoebiasis and to bypass hepatic metabolism. The work aimed to prepare, taste-masking oral disintegrating tablets of metronidazole using different proportions of the drug and disintegrants in various ratios by an effervescent method. The ODT was developed by direct compression with various concentrations of super disintegrating agents (1-7%). In this technique, sodium bicarbonate and tartaric acid were used to generate effervescence. The formulated tablets were assessed for physicochemical characteristics. The results of FTIR spectroscopy indicated the stable character of metronidazole. In vitro studies revealed that batch F6 was having a 97.65% cumulative amount of drug release at 20th minute compared to other formulations. Due to the effervescent method, there was a significant increase in drug release, seen at the 1:1.5 ratio. Taste evaluation studies were conducted on healthy human volunteers.

Enhanced bioavailability and antihypertensive activity of nisoldipine loaded nanoemulsion: optimization, cytotoxicity and uptake across Caco-2 cell line, pharmacokinetic and pharmacodynamic studies

Objective: The present study explored the antihypertensive activity of nisoldipine in oil in water nanoemulsion to improve its oral bioavailability via intestinal lymphatic uptake. Methods: Nanoemulsion was prepared by ultrasonication technique using Peceol, Cremophor EL and Transcutol HP as oil, surfactant and cosurfactant respectively. Optimization was done employing 32 full factorial design. The developed formulation was assessed for in vitro,cell line, ex vivo and in vivo studies. Results: The experimental results indicated homogeneity of the nanoemulsion with globule size of 62.35 ± 2.55 nm and PDI value of 0.108 ± 0.01 with negative zeta potential (−26.2 ± 3.6 mV). Transmission electron microscopy showed spherical oil globules morphology. The in vitro diffusion study showed significant increase in drug release from NE formulations (98.51 ± 2.64%) as compared to plain drug dispersion (29.73 ± 2.15%) in 0.1 N HCl + 0.5% SLS medium. Moreover, higher quantitative and qualitative uptake of nanoemulsion via Caco-2 cells showed superior intestinal absorption and improved therapeutic activity of nisoldipine when compared to drug dispersion. Pharmacokinetic and pharmacodynamic study confirmed significantly (p ˂ 0.05) greater bioavailability and antihypertensive activity of nisoldipine nanoemulsion when compared to its dispersion. These results are visualized in abstract figure. Conclusion: Thus, prepared nanoemulsion showed potential as oral delivery system for nisoldipine with superior oral bioavailability and therapeutic efficacy over drug dispersion.

IN SITU GEL AS PLATFORM FOR KETOCONAZOLE SLOW RELEASE DOSAGE FORM

Objective: The aim of this study was to formulate ketoconazole (keto) as oral floating in situ gel to slow the release of keto in the stomach.Methods: Sodium alginate (Na alginate) was used as a primary polymer in the preparation of the in situ gel and was supported by the following polymers: guar gum (GG), hydroxypropyl methylcellulose (HPMC) K4M, K15M and carbapol 940 as viscosity enhancing agents. As a consequence, and to complete the gelation process of above formulations was by adding the calcium carbonate (CaCO3). The in situ gels were investigated by the following tests: floating lag time, floating duration, viscosity, drug content, in vitro gelling studies and in vitro release study.Results: The study showed that the faster release was obtained with F1 which contained Na alginate alone. Additionally, reduction in Na alginate concentration resulted in significant increase in drug release. It was also noted that the increase in GG (viscosity enhancing polymer) concentration resulted in non-significant decrease in percent drug release and the reduction in CaCO3 concentration led to significant increase in drug release. Moreover, the release of drug was also affected by grade of viscosity enhancing polymer, the faster release was observed with the formula which contained a polymer of low viscosity (HPMC K4M) and an opposite result was with the high viscosity polymer (HPMCK15M).Conclusion: This study showed the formulation of Na alginate with GG and CaCO3, led to gain floating in situ gel and a sustained release of keto.

Development and In vitro Evaluation of Self-Adhesive Matrix-Type Transdermal Delivery System of Ondansetron Hydrochloride

Purpose: To develop and evaluate self-adhesive matrix-type ondansetron hydrochloride (OND) transdermal formulation.Methods: OND transdermal patches were prepared using solvent casting method. The matrix polymer composition was Eudragit E 100, polyvinyl pyrrolidone and either propylene glycol or dibutyl sebacate as plasticizer. Mean patch thickness, tensile strength, moisture content, water absorption capacity and drug content of the patches were studied. In vitro release and permeation of the patches were determined using Franz diffusion cell.Results: Mean patch thickness, moisture content, and water uptake increased with increased contents of polyvinyl pyrrolidone (PVP) and plasticiser. Higher levels of PVP and plasticiser increased drug release. Addition of release modifier such as succinic acid (SA) and myristic acid (MA) to the patch formulations produced a significant increase in drug release from the patch. Higuchi plots for patches containing propylene glycol (PG) were non-linear (r2 = 0.9564), indicating that they did not follow Higuchi release model whereas the plots for most of the patches containing dibutyl sebacate (DBS) followed Higuchi release model (r2 = 0.9974).Conclusion: DBS is a superior plasticiser to PG for OND matrix patches while succinic acid (SA) is a more effective release modifier than myristic acid (MA) for PG patches.Keywords: Ondansetron hydrochloride, Drug release, Release modifier, Transdermal, Dibutyl sebacate, Succinic acid, Higuchi model, Plasticizer

Component Screening of Miconazole Nitrate Nanoemulsion

The aim of the present study was to investigate the potential of a nanoemulsion formulation for vaginal delivery of Miconazole Nitrate(MCZ). Various oil-in-water nanoemulsions were prepared by the spontaneous emulsification method. The nanoemulsion area was identified by constructing pseudoternary phase diagrams. The prepared nanoemulsions were subjected to different thermodynamic stability tests. The nanoemulsion formulations that passed thermodynamic stability tests were characterized for pH, refractive index, viscosity, droplet size, drug content, transmission electron microscopy, stability study and in vitro drug release through modified dissolution apparatus. A significant increase in drug release, and good in vitro and in vivo antifungal efficacy were observed in optimized NE formulation F4 which consist of 1%wt/wt MCZ, 20%wt/wt Captex200EP, 40% wt/wt Twen80:CapmulMCM(2:1) and 40% wt/wt distilled water. In vitro antifungal efficacy of formulation F4 showed a significant increase in percent inhibition when compared with MCZ cream on candida albicans induced vaginal infection in mice. These results suggested that NEs are potential vehicles for improved vaginal delivery of MCZ.

Nanoemulsions as self-emulsified drug delivery carriers for enhanced permeability of the poorly water-soluble selective β1-adrenoreceptor blocker Talinolol

To enhance the bioavailability of the poorly water-soluble drug talinolol, a self-nanoemulsifying drug delivery system (SNEDDS) comprising 5% (w/v) Brij-721 ethanolic solution (Smix), triacetin, and water, in the ratio of 40:20:40 (% w/w) was developed by constructing pseudo-ternary phase diagrams and evaluated for droplet size, polydispersity index, and surface morphology of nanoemulsions. The effect of nanodrug carriers on drug release and permeability was assessed using stripped porcine jejunum and everted rat gut sac method and compared with hydroalcoholic drug solution, oily solution, and conventional emulsion and suspension. The SNEDDS showed a significant (P < 0.001) increase in drug release, permeability, and in vivo bioavailability as compared to drug suspension. This may be attributed to increased solubility and enhanced permeability of the drug from nanosized emulsion. From the Clinical EditorIn this study, a self-nanoemulsifying drug delivery system was utilized to enhance the bioavailability of the poorly water-soluble beta-blocker talinolol. Significant increase in drug release, permeability, and in vivo bioavailability were demonstrated as compared to standard drug suspension.

In vitro dissolution of oral modified-release tablets and capsules in ethanolic media

In 2005, Palladone, an extended-release capsule, was withdrawn from the market after clinical testing showed subjects who took the product with alcohol had increased levels of drug in their blood. To better understand this phenomenon, we studied the in vitro drug release of 27 oral modified-release products in alcohol-containing media. In 40% alcoholic medium, 9 of 10 capsules and 2 of 17 tablets show accelerated drug release. When a high percentage of the total dose is released in a short period of time, the extended-release product is then performing like an immediate release formulation. Products were also tested in 5% and 20% alcoholic media and in simulated gastric fluid (without enzyme) containing 20% alcohol. No tested capsules or tablets exhibited a significant increase in drug release in media containing only 5% alcohol. The current study indicates that in vitro dissolution may provide evidence regarding the ruggedness of formulations to ingested alcohol.

Development and characterization of colon specific drug delivery system bearing 5-ASA and camylofine dihydrochloride for the treatment of ulcerative colitis

The treatment of ulcerative colitis (inflammatory bowel disease, IBD) has been achieved by using colon specific drug delivery system bearing 5-ASA and Camylofine dihydrochloride. Chitosan microspheres were prepared separately for both the drugs using emulsion method followed by enteric coating with Eudragit®S-100. The in vitro drug release was investigated in different simulated GIT medium. The drug release in PBS (pH7.4) and simulated gastric fluid has shown almost similar pattern and rate, whereas a significant increase in drug release (70.3 ± 1.36 and 72.5 ± 1.33% of 5-ASA and Camylofine, respectively) was observed in medium containing 3% rat caecal matter, after 24 h. In control study, 57.1 ± 1.13% of 5-ASA and 59.2 ± 1.2% of Camylofine release was observed in 24 h. For enzyme induction, rats were orally administered with 1 mL of 1% w/v dispersion of chitosan for 5 days and release rate studies were conducted in SCF with 3% w/v of caecal matter. An enhanced drug release (i.e., 92.3 ± 3.81 and 95.5 ± 3.52% 5-ASA and Camylofine, respectively) was observed after 24 h in dissolution medium containing 3% caecal content obtained from enzyme induced animals. In vivo data showed that microspheres delivered most of its drug load (76.55 ± 2.13%) to the colon after 9 h, which reflects its targeting potential to the colon. It is concluded that orally administered microspheres of both drugs can be used together for the specific delivery of drug to the colon and reduce symptoms of ulcerative colitis.

Cross-Linked Guar Gum Hydrogel Discs for Colon-Specific Delivery of Ibuprofen: Formulation and In Vitro Evaluation

Hydrogel discs of guar gum cross-linked with glutaraldehyde were prepared as vehicles for colon-specific drug delivery. Ibuprofen was chosen as model drug. The discs were evaluated for such parameters as size, shape, weight, and drug loading. Swelling (buffer uptake) and in vitro drug release study, in presence and absence of rat caecal contents, was performed in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 7.4) to evaluate the effect of various formulation parameters like guar gum concentration, amount of cross-linking agent, and cross-linking time on drug release. Cross-linking resulted in significant reduction in swelling of guar gum. Significant increase in drug release was observed in medium containing rat caecal content. Percent drug release increased with increasing glutaraldehyde concentration. Cross-linking time and guar gum concentration did not have any significant effect on drug release in the range studied.

Preparation and evaluation of diltiazem hydrochloride-gelucire 43/01 floating granules prepared by melt granulation

The basic objective of this study was to explore the application of Gelucire 43/01 for the design of multi-unit floating systems of a highly water-soluble drug diltiazem HCl. Diltiazem HCl-Gelucire 43/01 granules were prepared by melt granulation technique. The granules were evaluated for in vitro and in vivo floating ability, surface topography, and in vitro drug release. Aging effect on storage was evaluated using scanning electron microscopy, hot stage polarizing microscopy (HSPM), differential scanning calorimetry (DSC), and in vitro drug release. Granules were retained in stomach at least for 6 hours. Approximately 65% to 80% drug was released over 6 hours with initial fast release from the surface. Surface topography, HSPM, DSC study of the aged samples showed phase transformation of Gelucire. The phase transformation also caused significant increase in drug release. In conclusion, hydrophobic lipid, Gelucire 43/01, can be considered as an effective carrier for design of a multi-unit floating drug delivery system of highly water-soluble drugs such as diltiazem HCl.

Bimodal drug release achieved with multi-layer matrix tablets: transport mechanisms and device design

The aim of this study was to develop new multi-layer matrix tablets to achieve bimodal drug release profiles (fast release/slow release/fast release). Hydroxypropyl methylcellulose acetate succinate (HPMCAS, type MF) was chosen as a matrix former, because it is water-insoluble at low, and water-soluble at high pH values. Studies focused on the elucidation of the drug release mechanisms from HPMCAS-MF:drug tablets. In 0.1 N HCl the resulting release kinetics can be described using Fick’s second law of diffusion, taking into account axial and radial mass transfer in cylindrical geometry. As the diffusion coefficients are found to be constant and the boundary conditions to be stationary, these systems are purely drug diffusion-controlled. In contrast, the dominating mass transport phenomena in phosphate buffer pH 7.4 are more complex. Due to polymer dissolution the resulting matrix structure is time-variant, leading to increasing drug diffusion coefficients and decreasing tablet dimensions, and thus moving boundary conditions. Drug release is affected by water imbibition, drug diffusion and polymer dissolution and is faster compared to 0.1 N HCl. With knowledge of these underlying release mechanisms, multi-layer matrix tablets were developed to achieve bimodal drug release. HPMCAS-MF:drug mixtures were used as tablet cores. As expected, changing the release medium from 0.1 N HCl to phosphate buffer pH 7.4 after 2 h, lead to a significant increase in drug release. The abruptness of this rate change could be enhanced by adding two drug-free HPMCAS-MF barrier layers (one on each side) to the system. The addition of a fourth, drug-containing and fast disintegrating initial dose layer yielded the desired bimodal drug release patterns. The process and formulation parameters affecting the resulting release rates were investigated using theophylline and acetaminophen as model drugs.