Evaluation Of Drug Release Research Articles

Patterns of drug release as a function of drug loading from amorphous solid dispersions: A comparison of five different polymers.

To reduce the pill burden associated with amorphous solid dispersions (ASDs), which arises from the large quantity of polymer used in the formulation, it is of interest to understand the relationship between drug loading and release properties. The aim of this study was to comprehensively evaluate drug release mechanisms from ASDs with polymers of varying hydrophobicity as a function of drug loading. Surface normalized dissolution rates of drug and polymer were studied for felodipine ASDs with polyvinylpyrrolidone (PVP), polyvinylpyrrolidone/vinyl acetate (PVPVA), EudragitⓇ S 100 (EUDS), hydroxypropylmethylcellulose (HPMC), and hydroxypropylmethylcellulose acetate succinate (HPMCAS), as a function of drug loading. The water sorption profiles and water contact angle measurements suggested the following rank order for hydrophobicity of the different polymers: HPMCAS ≃ EUDS > HPMC > PVPVA > PVP. For ASDs with relatively hydrophilic polymers (PVP, PVPVA and HPMC), drug release rates were polymer-controlled at low drug loadings (≤15%), whereas at higher drug loadings, release rates were more similar to that of the amorphous drug. The sudden decline in the release performance of ASDs with hydrophilic polymers when a certain drug loading was reached, was attributed to water-induced phase separation. For ASDs with more hydrophobic polymers (HPMCAS and EUDS), the dissolution rate of both drug and polymer was polymer-controlled for drug loadings as high as 50%, with a more gradual decline in drug release rate at higher drug loadings. Notably, at low drug loadings and across the different polymers, when the polymer dictated the drug release rate, ASDs prepared with the most hydrophilic polymers showed the fastest drug release. This suggested a ‘trade-off’ in choosing between higher release rates with more hydrophilic polymers at low drug loadings and higher drug loadings achievable with more hydrophobic polymers at the expense of lowered release rates. The findings described herein have significant implications for rational selection of polymers for formulation of ASDs with high drug loading and enhanced dissolution performance.

Evaluation of diclofenac sodium incorporation in alginate membranes as potential drug release system

In this study, we proposed the use of the biopolymer alginate to produce membranes with diclofenac sodium incorporated as model-drug aiming at wound dressing application with drug delivery. The membranes were prepared by casting and the drug was incorporated directly into alginate solution, being retained within the membrane. Morphological, chemical, mechanical and barrier properties were evaluated, as well as the release kinetics in vitro using simulated exudate fluid at 37 °C. Results show that the membranes are malleable in the glycerol presence and more resistant to water after crosslinking. The incorporation of diclofenac sodium did not affect barrier properties, but influenced the mechanical properties, increasing the total thickness (from 0.108 to 0.209 mm) and reducing tensile strength (from 40.85 to 21.76 MPa). Drug release evaluation shows that anomalous transport is the major rate-controlling mechanism, where the swelling or erosion of the alginate matrix is the major responsible for the diclofenac sodium release, with a small contribution of Fickian diffusion mechanism. The results show the potential of application of the alginate membranes for wound dressings with drug delivery for enhancing healing process.

Facile preparation of pH-sensitive chitosan microspheres for delivery of curcumin; characterization, drug release kinetics and evaluation of anticancer activity

Curcumin (CUR) is a lowly water-soluble natural polyphenol with chemopreventive and chemotherapeutic activities. Hence, to achieve the system with good CUR loading ability, porous MIL-88 (Fe) was prepared in the presence of the presynthesized graphene quantum dots (GQDs) (GQDs@MIL-88 (Fe)). In the following, CUR loaded in the fabricated GQDs@MIL-88 (Fe) nanohybrid. The characterization techniques; Fourier transform infrared (FT-IR), X-ray powder diffraction (XRD), scanning electron microscope (SEM), photoluminescence (PL), and Brunauer–Emmett–Teller (BET) analysis showed success in the synthesis of GQDs@MIL-88 (Fe). Moreover, the FT-IR analysis displayed the loading of CUR and the formation of CUR@GQDs@MIL-88(Fe). Chitosan (CS) was used as a green coating to enhance the biocompatibility of the prepared system (CS/CUR@GQDs@MIL-88(Fe). The fabricated microspheres showed pH-sensitive swelling behavior and released 38.3% of CUR in pH 5.0 which is better fitted with the First-order kinetic model (R2 = 0.9726). In comparison with CUR@GQDs@MIL-88(Fe), the MTT and DAPI assay exhibited less toxic effect for CS/CUR@GQDs@MIL-88(Fe) against MDA-MB 231 cells. Moreover, the safety of the CS/CUR@GQDs@MIL-88(Fe) confirmed after incubation against MCF 10A as a model of the normal cell line. The results conveyed a new concept that the CS/CUR@GQDs@MIL-88(Fe) is a potential candidate for using as a biocompatible carrier with controlled drug delivery ability.

Ammonium glycyrrhizate skin delivery from ultradeformable liposomes: A novel use as an anti-inflammatory agent in topical drug delivery

Glycyrrhiza glabra L. is a native plant of Central and South-Western Asia that is also diffused in the Mediterranean area and contains several bioactive compounds such as: flavonoids, sterols, triterpene and saponins. Glycyrrhizin, containing glycyrrhizic and glycyrrhizinic acids has anti-inflammatory and antiallergic effects that are similar to corticosteroids. Ammonium glycyrrhizinate is a derivative salt of glycyrrhizic acid with similar anti-inflammatory activity that cannot pass through the skin due to its physicochemical properties and molecular weight. Although several nanoformulations, such as ethosomes, are designed to provide a systemic effect through a topical application, there are different limitations to the distribution inside the blood stream. For this reason, ultradeformable liposomes, or transfersomes, are selected to improve the topical delivery of drugs and allow the distribution of payloads in the blood stream because they pass intact through the stratum corneum epidermis barrier, due to the presence of sodium cholate, aqueous cutaneous gradient, and the rapid penetration of transfersomes by cutaneous tight junctions, thus allowing the systemic delivery of different therapeutic cargo in non-occlusive conditions. The aim of this work was the synthesis and physicochemical characterization of the ammonium glycyrrhizinate-loaded ultradeformable liposomes, the evaluation of drug release and permeation through stratum corneum and epidermis barrier. The in vivo anti-inflammatory effect of ammonium glycyrrhizinate-loaded ultradeformable liposomes was tested on human healthy volunteers. The results demonstrated that the ammonium glycyrrhizinate-loaded ultradeformable liposomes decreased the skin inflammation on the human volunteers and the resulting nanoformulations can be used as a potential topical drug delivery system for anti-inflammatory therapy.☆Parts of these results were presented as a poster communication at the Recent Developments in Pharmaceutical Analysis 2019 (RDPA 2019), Chieti, Italy.

Sol–Gel Treatment of Textiles for the Entrapping of an Antioxidant/Anti-Inflammatory Molecule: Functional Coating Morphological Characterization and Drug Release Evaluation

The growing interest towards textile-based drug delivery systems is due to their potential innovative medical and well-being applications. In recent years, the technique of encapsulation or inclusion of the medicine/active principle into a polymer functional matrix has been employed in order to obtain textile materials with controlled drug release. In this study, a sol–gel-based coating was developed and used as an entrapping polymeric cross-linked network for a N-Palmitoyl-ethanolamine (PEA) derivative, 2-methyl-pentadecanoic acid (4-nitro-phenyl)-amide or N-Palmitoyl-(4-nitro-phenyl)-amine (PNPA), whose anti-inflammatory and antioxidant properties have already been shown. A wide series of chemical-physical methods have been used to characterize the silica-based functional sol and to ascertain the efficient and temporary deposit of PNPA on the sol–gel coated cotton fabrics. The medicine release system achieved was shown to ensure biocompatibility, PNPA reservoir and its subsequent releasing under the action of cutaneous stimuli, thus providing useful insights in the design of medical textiles.

Sensitivity of Different In Vitro Performance Tests and Their In Vivo Relevance for Calcipotriol/Betamethasone Ointment.

We compared results of in vitro performance testing with results of therapeutic equivalence study for calcipotriol/betamethasone ointment, to evaluate their sensitivity and in vivo relevance. Different in vitro methods were used to evaluate drug release and permeation from the test and reference ointment. Moreover, 444 psoriasis patients were randomized in the therapeutic equivalence study and the parameters of efficacy and safety were compared with in vitro results. In vitro release and permeation rate of calcipotriol and betamethasone from the test formulation was higher than from the reference product for all methods used (p ≤ 0.05 for calcipotriol and p < 0.01 for betamethasone). Observed batch-to-batch variability of reference product confirmed high sensitivity and discriminatory power of in vitro methods. Higher release and permeation rate of calcipotriol and betamethasone from test product was reflected in the efficacy assessment (mean response difference 4.78 mPASI percentage points), but the observed difference was within the equivalence margins. Systemic exposure to calcipotriol and betamethasone was similar in both treatment groups. The results of in vitro experiments rank orderly correlated with the results of clinical study. In vitro methods are more sensitive and highly discriminatory when compared to in vivo performance.

Assessment of “Sameness” and/or Differences between Marketed Creams Containing Miconazole Nitrate Using a Discriminatory in vitro Release Testing (IVRT) Method

In vitro release testing (IVRT) provides an efficient method for the evaluation of drug release from semi-solid formulations. The aim of this research was to develop and validate a discriminatory IVRT system using vertical diffusion cells (VDCs) to assess generic topical products containing miconazole nitrate (MCZ). A comprehensive approach addressing all essential suitability criteria supporting the reliability of IVRT results was applied. These include mechanical validation of the VDCs, a performance verification test (PVT), validation of the analytical method (HPLC) used to quantify the drug release and validation of the IVRT method to confirm its precision, reproducibility, discriminatory ability, and robustness. Two marketed generic products were tested and assessed in accordance with the acceptance criteria for “sameness” in the FDA’s SUPAC-SS guidance which requires that the 90% confidence interval (CI) should fall within the limits of 75%–133.33%. One product was found to be in vitro equivalent to the reference product whereas the other was not. The results confirmed the suitability of the IVRT method to accurately measure the release of MCZ from topical cream products and, importantly, demonstrated the necessary discriminatory ability to assess “sameness”/differences of dermatological creams containing MCZ. Furthermore, the developed IVRT method was able to detect differences between formulations, which may be attributed to qualitative (Q1) and quantitative (Q2) properties and the microstructure and arrangement of matter (Q3).

Formulation and Evaluation of Floating and Mucoadhesive Tablets containing Repaglinide

In the present study, Repaglinide an anti-diabetic drug is formulated in the form of floating mucoadhesive tablets to improve its bioavailability. Hydroxy Propyl Methyl Cellulose K200M, Sodium Carboxy Methyl Cellulose, Carbopol 974P, Karaya gum, Chitosan, Xanthan gum were used as rate controlling and mucoadhesive polymers in designing the tablets. Various formulations were prepared by using different concentration of polymers. The pre-compression blend of Repaglinide mucoadhesive tablets were characterized with respect to angle of repose, bulk density, tapped density, carr's index and hausner's ratio and all the results indicated that the blend had good flow property and better compressibility. The swelling studies were performed and the results indicated that all the formulations had good swelling index. The results of floating lag time and buoyancy studies suggested that formulations had good floating ability. The drug release studies indicated a controlled and enhanced drug release for a period of 12hrs. In-vivo study was carried out using the optimized formulation. Based on the in-vitro drug release and other related evaluation tests, formulation RT11 containing drug: karaya gum in the ratio 1: 2 was optimized. The drug release of the formulation RT11 followed Higuchi model with regression value of 0.984.

&lt;p&gt;Ionically Cross-Linked Chitosan Nanoparticles for Sustained Delivery of Docetaxel: Fabrication, Post-Formulation and Acute Oral Toxicity Evaluation&lt;/p&gt;

IntroductionPolymeric nanoparticles are potential carriers for the efficient delivery of hydrophilic and hydrophobic drugs due to their multifaceted applications. Docetaxel is relatively less hydrophobic and twice as potent as paclitaxel. Like other taxane chemotherapeutic agents, docetaxel is not well tolerated and shows toxicity in the patients. Nanoencapsulation of potent chemotherapeutic agents has been shown to improve tolerability and therapeutic outcome. Therefore, the present study was designed to fabricate chitosan and sodium tripolyphosphate (STPP) based on ionically cross-linked nanoparticles for sustained release of docetaxel.MethodsNanoparticles were prepared by the ionic-gelation method by dropwise addition of the STPP solution into the chitosan solution in different ratios. CNPs were characterized for post-formulation parameters like size, zeta potential, scanning electron microscope (SEM), FTIR, DSC/TGA, pXRD, and in-vitro drug release, as well as for acute oral toxicity studies in Wistar rats.Results and discussionThe optimized docetaxel loaded polymeric nanoparticles were in the size range (172.6nm–479.65 nm), and zeta potential (30.45–35.95 mV) required to achieve enhanced permeation and retention effect. In addition, scanning electron microscopy revealed rough and porous surface, whereas, FTIR revealed the compatible polymeric nanoparticles. Likewise, the thermal stability was ensured through DSC and TG analysis, and powder X-ray diffraction analysis exhibited solid-state stability of the docetaxel loaded nanoparticles. The in-vitro drug release evaluation in phosphate buffer saline (pH 7.4) showed sustained release pattern, i.e. 51.57–69.93% within 24 hrs. The data were fitted to different release kinetic models which showed Fickian diffusion as a predominant release mechanism (R2= 0.9734–0.9786, n= 0.264–0.340). Acceptable tolerability was exhibited by acute oral toxicity in rabbits and no abnormality was noted in growth, behavior, blood biochemistry or histology and function of vital organs.ConclusionIonically cross-linked chitosan nanoparticles are non-toxic and biocompatible drug delivery systems for sustained release of chemotherapeutic agents, such as docetaxel.

Prilling of API/fatty acid suspensions: Processability and characterisation.

Current study evaluated the processability and characteristics of prills made of an active pharmaceutical ingredient/fatty acid (API/FA) suspension instead of previously studied API/FA solutions to enlarge the application field of prilling. Metformin hydrochloride (MET) and paracetamol (PAR) were used as model APIs while both the effect of drug load (10-40%) and FA chain length (C14-C22) were evaluated. API/FA suspensions were processable on lab-scale prilling equipment without thermal degradation, nozzle obstruction or sedimentation in function of processing time. The collected prills were spherical (AR ≥ 0.898) with a smooth surface (sphericity ≥ 0.914) and a particle size of ±2.3 mm and 2.4 mm for MET and PAR prills, respectively, independent of drug load and/or FA chain length. In vitro drug release evaluation revealed a faster drug release at higher drug load, higher API water solubility and shorter FA chain length. Solid state characterisation via XRD and Raman spectroscopy showed that API and FA crystallinity was maintained after thermal processing via prilling and during storage. Evaluation of the similarity factor indicated a stable drug release (f2 > 50) from MET and PAR prills after 6 months storage at 25 °C or 40 °C.

In Vitro Methods for Evaluating Drug Release of Vaginal Ring Formulations-A Critical Review.

The vagina is a promising site for both local and systemic drug delivery and represents an interesting administration route for compounds with poor oral bioavailability. Whereas most of the currently marketed dosage forms were designed as immediate release formulations, intravaginal rings (IVRs) offer the possibility of a controlled vaginal drug delivery over several weeks or months. For a long time, the development of IVRs was limited to steroid-releasing formulations. Recently, IVRs have witnessed a surge of new interest as promising delivery systems for microbicides. Therefore, various novel IVR designs have been introduced. To ensure that only safe and effective IVRs will be administered to patients, it is important to properly distinguish between IVRs with desired and undesired release performance. In vitro methods for evaluating drug release of IVRs that present with sufficient predictive capacity for in vivo drug release, and discriminatory power with regard to IVRs quality, are an essential tool for this purpose. The objective of the present review article is to present the current status of in vitro drug release testing of IVRs and to critically discuss current compendial and non-official in vitro drug release methods with regard to their discriminatory power and in vivo predictivity.

Conductive polymeric film loaded with ibuprofen as a wound dressing material

In current study, sodium alginate/gelatin/hyaluronic acid/reduced graphene oxide (SAlg/Gel/HA/RGO) electroconductive composite polymeric films were fabricated for wound dressing applications. In the production of composite film, while SAlg/Gel/HA was used as a polymeric network, RGO (0, 10, 20% v/v) was employed as an electroactive material. Produced films were characterized by FT-IR, XRD and SEM analyses. In order to observe potential usage of desired material as a wound dressing, electroconductive and mechanical performances, swelling behavior, water vapor transmission rate (WVTR), oxygen permeability and cytotoxicity of the films were investigated by concerned test method. To improve the healing effect of the films and reduce pain in the wound, they were loaded with ibuprofen, which is an anti-inflammatory drug. The drug release evaluations showed that SAlg/Gel/HA/RGO films were more effective than pure films for controlled release of the model drug. All results suggested that SAlg/Gel/HA/RGO electroconductive polymeric films have a great potential for wound dressing material in the future applications.

Enhanced Skin Permeation of Hydrocortisone Using Nanoemulsion as Potential Vehicle

AbstractThe current work was performed to estimate the solubility and Hansen solubility parameters of a poorly soluble corticosteroid hydrocortisone (HCN) in various components of nanoemulsion and to enhance the skin permeation rate of HCN using nanoemulsions as potential vehicles. Screening studies suggested the use of Capryol‐90 (oil), Triton‐X100 (surfactant) and Transcutol‐HP (cosurfactant) in the preparation of HCN nanoemulsions. HCN nanoemulsions were developed using low energy emulsification technique and characterized for droplet size, plolydispersity index (PDI), zeta potential (ZP), refractive index (RI), percent of transmittance (% T) and transmission electron microscopy (TEM) and evaluated for drug release behavior. Selected nanoemulsions and control (HCN suspension) were subjected to in vitro skin permeation studies. Optimized formula HSN8 showed droplet size of 52.6 nm, PDI of 0.109, ZP of −33.72 mV, RI of 1.337 and % T of 97.68%. TEM confirmed spherical‐shaped droplets in nanometer range. In vitro drug release evaluation suggested significant release of HCN from optimized nanoemulsion (98.52%) compared with control (35.85%). Skin permeation profile of HCN from optimized nanoemulsion was also significant compared with control. These results suggested the potential of nanoemulsion in enhancing the transdermal delivery of HCN via rat skin.

Evaluating HIFU-mediated local drug release using thermal strain imaging: Phantom and preliminary in-vivo studies.

High-intensity focused ultrasound (HIFU)-mediated drug release becomes a promising therapeutic technique for treatment of cancer, which has merits of deep penetration, noninvasive approach and nonionizing radiation. However, conventional thermocouple-based approach for treatment monitoring would encounter big challenges such as the viscous heating artifact and difficulty in monitoring in the deep region. In this study, we develop an effective method based on thermal strain imaging (TSI) for the evaluation of HIFU-mediated drug release. Both phantom experiments and preliminary animal experiments were performed to investigate the feasibility of the proposed approach. Doxorubicin (DOX)-loaded cerasomes (HIFU and temperature-sensitive cerasomes, HTSCs) were prepared. In the phantom experiments, the HTSC solution is contained inside a cylindrical chamber within a tissue-mimicking phantom. In the animal experiments, the HTSCs are intravenously injected into tumor-bearing mice. An HIFU transducer is used to trigger DOX release from the HTSCs within the phantom or mice, and TSI is performed during HIFU heating. In the phantom experiments, the accuracy of temperature estimation using TSI is validated by measuring with a thermocouple. In animal experiments, the spatial consistency between the distribution of DOX released within the tumor and the location of the heating region estimated by TSI is validated using a spectrofluorophotometer. In the phantom experiments, the HTSCs show a burst release of DOX when the temperature of the HTSC solution estimated by TSI reaches about 42°C, which is in agreement with the condition for drug release from the HTSCs. The temperature estimation using TSI has high accuracy with error below 2.5%. In animal experiments, fluorescence imaging of the tumor validates that the heating region of HIFU could be localized by the low-strain region of TSI. The present framework demonstrates a reliable and effective solution to the evaluation of HIFU-mediated local drug delivery.

Interaction with Modified Cyclodextrin as a Way to Increase the Antimalarial Activity of Primaquine.

Malaria is still a dangerous disease that impacts specifically Africa, Asia, and Latin America. The development of therapies to overcome the parasite infection is an important challenge nowadays. The medicine primaquine (PQ) is used in the treatment, although several side effects and low oral bioavailability are reported. This work focused on the preparation and characterization of a complex between PQ and 2- hydroxypropyl-β-cyclodextrin (HPCD), besides performing release tests of this formulation. PQ:HPCD complexes were prepared at 1:1 and 1:2 molar ratios, by the lyophilization method. The association between PQ and HPCD was tested using UV-vis, infrared (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy and NMR techniques (chemical shift, Job Plot, DOSY, and ROESY). Tests were also conducted to evaluate drug release before and after complexation with HPCD. Results showed that there was a weak interaction of PQ with HPCD, forming non-inclusion complexes. These results were supported by FTIR results and spatial correlations between hydrogens from PQ with the external HPCD hydrogens. A 1:2 PQ:HPCD preferred molar ratio was determined by DSC and Job Plot experiments and the time to release 96% of the drug was 21.2 h slower after complexation. Conclusion indicate that PQ interacts poorly with HPCD, probably due to its hydrophilic character, as well as to its interaction with the external rim of HPCD. Our results demonstrate that there was a significant improvement in the release time after the complexation process, which could lead to an increase in the activity of the drug.

Scientific Coformer Screening, Preparation and Evaluation of Fenofibrate Tartaric Acid Cocrystal

Objective: This present study aims to screen pharmaceutical cocrystal of Fenofibrate and coformers. Further the preparation and evaluation of fenofibrate-coformer cocrystal and In-Vitro drug release and Ex-Vivo Permeation study was done. Material and Methods: The coformers for Fenofibrate were screened using molecular docking. The cocrystals produced were characterized using Differential Scanning Calorimetry (DSC), X-ray diffraction (XRPD) study and Infrared spectroscopy. Results: Cocrystal of Fenofibrate with tartaric acid was successfully prepared. The cocrystals displayed enhanced dissolution rate by 2.36 fold, similarly the ex-vivo drug uptake through everted chicken intestine model was improved by 4.38 fold. The formation of cocrystals of fenofibrate with tartaric acid was evaluated by DSC, IR and XRPD. Conclusion: The fenofibrate - tartaric acid cocrystal exhibited increased % drug release and permeation compared to fenofibrate. This study confirms that selection of proper coformer is very vital step in preparation of stable, superior cocrystal. Based upon above study and results it revealed that cocrystallization offers a valuable way to improve the physicochemical properties of the API. Keywords: Pharmaceutical Cocrystal, Fenofibrate , Coformer, Molecular docking.

In-Vitro Evaluation of Drug Release and Antioxidant Activity of Aloe Loaded Chitosan Nanoparticles

Antioxidants play significant responsibility during the treatment of cancer and it’s adverse effects, because in the treatment of cancer by using chemotherapy, free radicals are generated and these free radicals accumulated in the body and cause damage, side effect (such as neurodegenerated disease, atherosclerosis, depression, leukemia, skin disease, diabetes etc.) and even death due to the biological consequence. So, antioxidant inhibits the generation of new and destroys previously present free radicals. A recent study was aimed for novel approach of herbal nanoparticles to get improved efficacy of the drug with fewer side effects. In-vitro Evaluation of Drug Release and Antioxidant Activity of Aloe Loaded Chitosan Nanoparticles were includes in this research. Aloe has good antioxidant property, but in the form of nanoparticles formed with the help of chitosan polymer, it’s enhancing their stability, in-vitro release property. Chitosan is one of the best polymer for nanomedicine formulation because of their low toxicity and high compatibility. Six formulations of aloe loaded chitosan nanopaticles were prepared and evaluated as antioxidant study, in-vitro release and stability studies. Results have shown that the F6 was most stable, good release and high antioxidant property. So, it found that F6 was good formulation among all batches and these nanoparticles can be used as antioxidant agent during the treatment of cancer along with chemotherapeutic drugs for improve their effectiveness and reduce adverse effects. Keywords: Cancer, Chemotherapy, Herbal, Chitosan nanoparticles, Antioxidant.

Formulation and evaluation of Prednisolone retention enema as dispersible tablet and vehicle for the treatment of ulcerative colitis

Ulcerative colitis is a chronic idiopathic inflammatory bowel disease that causes chronic inflammation and damage in the gastrointestinal (GI) tract that typically presents in the second or third decade of life with bloody diarrhoea and abdominal cramps. The objective of the present work was to formulate and evaluate of Prednisolone retention enema as a dispersible tablet and it is suspended in suitable vehicle for the treatment of ulcerative colitis. In the present work, an attempt has been made to formulate and evaluate Prednisolone retention enema as a dispersible tablet by using three different methods (direct compression (F1 to F3, wet granulation (F4 and F5) and slugging method (F6)). Prepared dispersible tablets were administered with the help of vehicle for the effective treatment of ulcerative colitis. Dispersible tablets were evaluated for various parameters. In vitro drug release and microbiological evaluation studies were performed to the best formulation in rectal suspension. Then the best formulation was subjected to carry out for stability studies at three different temperatures. Among the six formulations, F6 formulation showed better results. FT-IR study showed that there was no interaction between a drug and excipients. In vitro drug release and microbiological evaluation studies were performed for F6 formulation in rectal suspension. About 99.06 % of the drug was released at 60 min. and also it was found to be microbiologically stable. Results from the stability studies showed that F6 formulation alone and with rectal suspension was stable for a period of 90 days. It was concluded that F6 formulation in rectal suspension possesses a promising future for the treatment of ulcerative colitis.

A novel controlled release tetrandrine-loaded PDLLA film: evaluation of drug release and anti-adhesion effects in vitro and in vivo

To investigate the drug release and anti-adhesion effects of a TET (tetrandrine)-loaded PDLLA (poly-dl-lactide) film. Detection of TET release in vitro was carried out by high-performance liquid chromatography (HPLC) every 2 days following immersion of the tetrandrine-loaded PDLLA film in simulated body fluid until the TET content of the eluate could not be detected. For the in vivo test, TET-loaded PDLLA films were implanted into animal laminectomy models and positive and blank control groups were also set up. Postoperative serum tests, and macroscopic and histological analyses at 1, 4, 8, and 12 weeks, were used to assess the effects of the film. Statistical analyses were performed by one-way ANOVA. The drug release of the tetrandrine-loaded PDLLA film in vitro showed two phases with a second release peak. Ultimately, the duration of continuous delivery was up to 66 days and the cumulative delivery rate was up to 93.18%. Scores for the proliferation of epidural scars or adhesion of the dura mater in the test group were much lower than those for the two control groups. Histological analysis revealed the test group had fewer inflammatory cells and fibroblasts, as well as fewer extracellular collagen fibers, and a lower histology score than those of the two control groups at all time points. Tetrandrine-loaded PDLLA film is a novel controlled drug release and anti-adhesion material in vitro and in vivo.

LIBERAÇÃO CONTROLADA DO FÁRMACO MEBENDAZOL A PARTIR DE UMA MATRIZ POLIMÉRICA NATURAL

Sistemas de liberação controlada de fármacos têm por objetivos principais minimizar a necessidade de doses tóxicas e propiciar melhor controle da liberação do princípio ativo ao longo do tempo quando comparado à forma convencional de administração. Neste trabalho foi preparado um sistema de liberação controlada do fármaco mebendazol (MDZ), que apresenta baixa absorção gastrointestinal pela sua baixa solubilidade em água, a partir de uma matriz polimérica biodegradável formada por alginato de sódio. O teste de intumescimento e a avaliação temporal da liberação do ativo in vitro foram realizados em meio que simula as condições do corpo humano. A avaliação da resistência ao meio fisiológico pela matriz polimérica com MDZ incorporado mostrou que a mesma permaneceu por mais de 72 h no meio fisiológico, enquanto que a avaliação do comportamento de dissolução e liberação do MDZ durante 8 h mostrou-se satisfatória com a liberação do ativo de forma lenta de gradual, o que demonstra o potencial dessa matriz para ser usado como um dispositivo oral de liberação controlada desse fármaco.