Development of a modified hard gelatin capsule for colon-targeted drug delivery of hydrogel-based piroxicam microparticles (original) (raw)
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Heliyon
The current study was to improve and control aceclofenac delivery prepared as biopolymer-based microparticles for effective colon-targeted drug delivery using modified gelatin capsules (MGCs) at different time intervals developed in two batches (C1 and C2). Microparticles were formulated with extracted mucuna gum using liquid paraffin oil (AC.LPO) and soybean oil (AC.SO) and evaluated in vitro for physicochemical performance and in vivo in rats. Encapsulation efficiency ranges from 54.48 AE 0.21% to 82.83 AE 0.22% for AC.LPO and 52.64 AE 0.11% to 80.36 AE 0.22% for AC.SO. SEM showed oblong and irregular shapes with porous and cracked surfaces. DSC showed low enthalpy and a very broad endothermic peak depicting high amorphous property. Delayed drug release was observed in the upper gastrointestinal tract with sustained release depicted in the lower gastrointestinal tract (GIT) using 3 and 9-h batch C1 of MGCs. AC.SO exhibited significantly (p < 0.05) higher antiinflammatory activity (86%) than AC.LPO (77%). Hence, aceclofenac colon delivery could be improved and controlled using biopolymer-based colon-targeted microparticles delivered with MGCs.
International Journal of Nanomedicine
Background: Piroxicam exhibits low oral bioavailability, due to its meager solubility in water. The intent of this study was to ameliorate the bioavailability of the drug by employing a solubility-enhancing encapsulation technique. Methods: Seven samples were formulated with piroxicam and gelatin using both solvent evaporation and electrospraying together. Evaluation of solubility and release rate in water and assessment of bioavailability in rats were carried out in comparison with piroxicam plain drug powder (PPDP). Other in vitro explorations were accomplished using powder X-ray diffraction analysis, differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, and Fourier-transform infrared spectroscopy. Results: All piroxicam-loaded gelatinnanocontainers (PLGNs) enhanced solubility and release of the payload in water. In particular, a PLGN formulation consisting of piroxicam and gelatin at a 1:8 (w:w) ratio presented about 600-fold the drug solubility of that shown by PPDP. Moreover, 85.12%±10.96% of the payload was released from this formulation in 10 minutes which was significantly higher than that dissolved from PPDP in 10 minutes (11.81%±5.34%). Drug content, drug loading, and encapsulation efficiency of this formulation were 93.41%±0.56%, 10.45%±0.06%, and 66.74%±6.87%, respectively. The drug loaded in PLGNs existed in the amorphous state, as confirmed by X-ray diffraction and differential scanning-calorimetry analyses, and was more stable when analyzed by thermogravimetric analysis. Moreover, Fourier-transform infrared spectroscopy analysis suggested nonexistence of any piroxicam-gelatin interaction in the formulation. In the scanning electron-microscopy image, PLGNs appeared as round, smooth particles, with particle size of <1,000 nm. Amelioration in bioavailability of piroxicam with the aforementioned PLGN formulation was fourfold that of PPDP. Conclusion: The PLGN formulation fabricated with piroxicam and gelatin at 1:8 (w:w) might be a promising system for enhanced biopharmaceutical performance of the drug.
2012
The purpose of this research was to established new polysaccharide for the colon targeted drug delivery system, its formulation and in vitro and in vivo evaluation. Microspheres containing chitosan and bora rice were prepared by simple emulsification phase separation technique using glutaraldehyde as cross linking agent and model drug used was glipizide. Results of trial batches indicated that polymer to drug ratio and stirring speed affects characteristics of microspheres. Microspheres were discrete, spherical and free flowing. Microspheres exhibited small particle size, higher percentage yield and also showed higher percentage of drug entrapment efficiency. A 3 full factorial design was employed to study the effect of independent variables, polymer to drug ratio (A), and stirring speed (B) on dependent variables, particle size, swelling index, drug entrapment efficiency and percentage drug release. The optimized batch C2 exhibited satisfactory drug entrapment efficiency 63% and dr...
Advances in Polymer Technology, 2014
Microcapsules of aceclofenac with pH-dependent release properties for achieving targeted delivery to colon were developed. A solvent evaporation technique was adopted for microcapsules preparation using Eudragit RS 100 as a retardant polymer. The microcapsules were found free flowing, whitish, and spherical in shape. The entrapment efficacies of microcapsules were 95.73, 85.67, and 84% for F1 (1:1), F2 (1:2), and F3 (1:3), respectively. The particle size was in the range of 12 ± 2.48 to 32 ± 2.20 μm. The X-ray diffraction and Fourier transforms infrared (FTIR) studies of prepared microcapsules illustrated that there was no interaction between drug and polymer. The dissolution performed in three different pH media (1.2, 6.8, and 7.4) at 37 ± 0.5°C elucidates negligible release at pH 1.2 for 2 h but changing the pH from 1.2 to 6.8, showed burst release after 4 h and then demonstrated a constant release rate at 7.4 pH. The time for half-life of microcapsules showed that drug release from F1 microcapsules was quicker than F2 and F3. The time for half-life of capsule filled microcapsules was 15.54, 17.40, and 20.08 h, respectively. The formulated microcapsules do not show the release in gastric medium but released at phosphate buffer pH 6.8 and 7.4.
Formulation and in Vitro Evaluation of Natural Polymers Based Microspheres for Colonic Drug Delivery
International Journal of Pharmacy and Pharmaceutical Sciences, 2010
The present study describes development and in-vitro evaluation of natural polymers based MTZ microspheres prepared by ionotropic gelation technique for delivering drug to colon. The current work aimed to evaluate the novel potential of ionotropic gelation technique to produce natural polysaccharides based microspheres bearing MTZ, a sparingly water soluble antiamoebic drug, with increasing entrapment efficiency by gluteraldehyde which increasing crossinking as well as reduced swelling ability of formulations with given prolonged colon targeting. The prepared microspheres were characterized by entrapment efficiency, particle size, micromaritic properties, in vitro release behavior, scanning electron microscopy (SEM), FTIR etc. MTZ loaded microspheres should high entrapment efficiency (75.2%). The in vitro drug release was using U.S.P.dissolution rate test basket type apparatus in different P H media, which was found to be affected by change in guar gum-alginate and glutaraldehyde concentration. The percentage of drug released after 12 hr. was increased up to 85.73%. The rate of drug release followed first order kinetics and numerical data fitted in peppas model. It is concluded that Metronidazole loaded guar gum-alginate based microsphere can be used effectively for the colon targeting.
The sole objective of this work was to design successful dosage oral forms of diclofenac sodium (DiNa)-loaded solid lipid microparticles (SLM) based on solidified reverse micellar solution (SRMS). Hot homogenization technique was employed to prepare DicNa SLM using a mixture goat fat and Phospholipon Õ 90 G as lipid matrix and Tween Õ-80 as mobile surfactant. Characterization based on percentage yield, morphology, particle size, zeta potential, percentage encapsulation, pH and stability of SLMs were investigated. Anti-inflammatory, gastrointestinal tract (GIT) sparing effect and pharmacokinetics were carried out in rat model after oral administration. Results showed that the SLMs were spherical and smooth. The optimized formulation (SLM-4) had particle size of 79.40 ± 0.31 mm, polydispersity index of 0.633 ± 0.190, zeta potential of À63.20 ± 0.12 mV and encapsulation efficiency of 91.2 ± 0.1% with good stability after 8 months of storage. The DicNa SLM had sustained release effect with good anti-inflammatory activity. Higher and prolonged plasma DicNa concentration was shown by the SLM-4 compared to pure drug and a conventional sample. These studies demonstrate that DicNa-loaded SLM based on SRMS could be a promising oral formulation for enhanced bioavailability, pharmacologic activity and gastrointestinal sparing effect of the NSAID, DicNa.
Design and development of hydrogel beads for targeted drug delivery to the colon
AAPS PharmSciTech, 2007
The purpose of this research was to develop and evaluate a multiparticulate system of chitosan hydrogel beads exploiting pH-sensitive property and specific biodegradability for colon-targeted delivery of satranidazole. Chitosan hydrogel beads were prepared by the cross-linking method followed by enteric coating with Eudragit S100. All formulations were evaluated for particle size, encapsulation efficiency, swellability, and in vitro drug release. The size of the beads was found to range from 1.04 ± 0.82 mm to 1.95 ± 0.05 mm. The amount of the drug released after 24 hours from the formulation was found to be 97.67% ± 1.25% in the presence of extracellular enzymes as compared with 64.71% ± 1.91% and 96.52% ± 1.81% release of drug after 3 and 6 days of enzyme induction, respectively, in the presence of 4% cecal content. Degradation of the chitosan hydrogel beads in the presence of extracellular enzymes as compared with rat cecal and colonic enzymes indicates the potential of this multiparticulate system to serve as a carrier to deliver macromolecules specifically to the colon and can be offered as a substitute in vitro system for performing degradation studies. Studies demonstrated that orally administered chitosan hydrogel beads can be used effectively for the delivery of drug to the colon.
International journal of pharmaceutics, 2017
The aim of this work was to investigate the efficient targeting and delivery of indometacin (IND), as a model anti-inflammatory drug to the colon for treatment of inflammatory bowel disease. We prepared fast disintegrating tablets (FDT) containing IND encapsulated within poly(glycerol-adipate-co-ɷ-pentadecalactone), PGA-co-PDL, microparticles and coated with Eudragit L100-55 at different ratios (1:1.5, 1:1, 1:0.5). Microparticles encapsulated with IND were prepared using an o/w single emulsion solvent evaporation technique and coated with Eudragit L-100-55 via spray drying. The produced coated microparticles (PGA-co-PDL-IND/Eudragit) were formulated into optimised FTD using a single station press. The loading, in vitro release, permeability and transport of IND from PGA-co-PDL-IND/Eudragit microparticles was studied in Caco-2 cell lines. IND was efficiently encapsulated (570.15±4.2μg/mg) within the PGA-co-PDL microparticles. In vitro release of PGA-co-PDL-IND/Eudragit microparticles...
Nanomedicine: Nanotechnology, Biology and Medicine, 2013
The limited bioavailability and rapid clearance of the anti-inflammatory drug Ibuprofen Sodium (IbS) necessitates repeated drug administration. To address this, injectable IbS loaded PEGylated gelatin nanoparticles (PIG NPs) of size ~200 nm and entrapment efficiency ~70%, providing sustained release in vitro were prepared by a modified twostep desolvation process. The developed nanomedicine, containing a range of IbS concentrations upto 1mg/mL proved to be non-toxic, hemocompatible and nonimmunogenic, when tested through various in vitro assays and was reaffirmed by in vivo cytokine analysis. HPLC analysis of intravenously administered PIG NPs showed a sustained release of IbS for ~4 days with improved bioavailability and pharmacokinetics when compared to bare IbS and IbS-loaded non-PEGylated GNPs. Histological analysis of liver and kidney revealed tissue integrity as in the control, indicating biocompatibility of PIG NPs. The results demonstrate improved plasma half-life of IbS when encapsulated within nanogelatin, thereby aiding reduction in its frequency of administration.
A Novel polyelectrolyte complex (PEC) Hydrogel for controlled drug delivery to the colon
2007
This work was aimed at preparing and evaluating a physically crosslinked hydrogel for the controlled release of diverse drugs to the distal intestine. A solution of fluorescein isothiocyanate dextran, MW 4400 Da (FD4), or a dispersion of micronized dexamethasone (DMS) was microencapsulated into a PEC hydrogel, composed of polycationic N-trimethyl chitosan (TMC) and polyanionic N-carboxymethyl chitosan (CMCh). A fine spray of a 1% CMCh solution containing 1% FD4 in solution or 0.1% DMS in dispersion was directed into a 2% TMC solution, then the resulting microcapsules (MCPS) were lyophilized. MCPS were analyzed by SEM and solid-state NMR. Drug release from MCPS was too fast, so these were compressed into matrices (weight 20 mg; diameter 6 mm; drug load 2.5%, with FD4, or 3.7%, with DMS) which were enteric coated. Drug release from matrices was studied simulating matrix transit across GI environments of different pHs, from stomach to proximal colon. The enteric film hindered release in stomach and proximal small intestine. After film dissolution at ileum pH, release occurred with a pattern described by the Peppas equation (n=0.6, with DMS; n=0.7, with FD4). As the pH changed from 7.4 to 6 (from ileum to ascending colon) MCPS were liberated from matrix surface. This phenomenon sustained the release rate. The present MCPS allow controlled doses of macromolecular or microparticulate drugs being uniformly loaded into controlled-release matrices based on a physically crosslinked, biodegradable hydrogel.