Evaluation of hydrophilic matrix tablets based on Carbopol® 971P and low-viscosity sodium alginate for pH-independent controlled drug release

Background: The aim of this study was to evaluate matrix tablets containing different ratios of Carbopol^® 971P (CP) to low-viscosity sodium alginate (SA) and assess their suitability for pH-independent controlled drug release. Methods: Two processing methods (physical mixing, PM and spray-drying, SD) were applied before compaction and the release from corresponding matrices was compared. The release from CP-SA PM matrices was also investigated using three model drugs (paracetamol, salicylic acid, and verapamil HCl) and two dissolution media (0.1 N HCl or phosphate buffer, pH?=?6.8), and the release rate, mechanism, and pH-dependence were characterized by fitting of Higuchi and Peppas models, and evaluation of similarity factor. Furthermore, swelling behavior of CP-SA matrix tablets was studied for evaluating its impact on drug release. Results: The processing method (SD or PM) markedly affected the drug release from CP-SA matrices. ANOVA tests showed significant effects of the CP:SA ratio and drug type on the release rate (expressed by the constant, K_H, from Higuchi model) and of the dissolution medium on the release mechanism (expressed by the exponent, n, from Peppas model). Similarity factor (f₂) indicated that the CP:SA ratios ≥?25:75 and ≥?50:50 were suitable for pH-independent release of paracetamol and salicylic acid, respectively, although for verapamil HCl, the matrix with low CP:SA ratio (0:100) showed remarkably reduced pH-dependence of release. Swelling parameters (water uptake and mass loss) were significantly changed with experimental variables (CP:SA ratio, medium, and time) and were in good correlation with drug release. Conclusion: Matrix tablets based on CP and SA form a potentially useful versatile system for pH-independent controlled drug release.     

A novel risperidone-loaded SAIB–PLGA mixture matrix depot with a reduced burst release: effects of solvents and PLGA on drug release behaviors in vitro/in vivo

The purpose of this study was to develop an in situ forming SAIB (sucrose acetate isobutyrate)-PLGA (poly (d, lactide-co-glycolide)) mixture matrix depot for sustained release of risperidone. The factors affecting the risperidone release kinetics were investigated to obtain further insight into the drug release mechanisms. The burst release in vitro was significantly reduced (4.95%) by using DMSO as solvent. And, increasing the PLGA content from 2 to 10% w/w decreased the initial release from 6.95 to 1.05%. The initial release in vivo decreased with increasing PLGA content (2.0% w/w PLGA, C _max = 1161.7 ± 550.2 ng ml⁻¹; 10% w/w PLGA, C _max = 280.3 ± 98.5 ng ml⁻¹). The persistence (AUC_4–20 days) over 20 days increased from 76.8 ± 20.7 to 362.8 ± 75.0 ng d ml⁻¹ by inclusion of 10% PLGA compared with the PLGA-free depot. These results demonstrate that the SAIB–PLGA mixture matrix depot could be useful as a sustained delivery system for risperidone.     

Preparation and evaluation of a timolol maleate drug–resin ophthalmic suspension as a sustained-release formulation in vitro and in vivo

Abstract

The aim of this work was to assess the performance of resin as an ocular delivery system. Timolol maleate (TM) was chosen as the model drug and an ion exchange resin (IER) as the carrier. The drug–resin complex was prepared using an oscillation method and then characterized regarding particle size, zeta potential, morphology, and drug content. After in vitro drug release study and corneal permeation study were performed, in vivo studies were performed in New Zealand albino rabbits using a suspension with particles sized 4.8?±?1.2?μm and drug loading at 43.00?±?0.09 %. The results indicate that drug released from the drug–resin ophthalmic suspension permeated the cornea and displayed a sustained-release behavior. Drug levels in the ocular tissues after administration of the drug–resin ophthalmic suspension were significantly higher than after treatment with an eye drop formulation but were lower in body tissues and in the plasma. In conclusion, resins have great potential as effective ocular drug delivery carriers to increase ocular bioavailability of timolol while simultaneously reducing systemic drug absorption.     

Does the performance of wet granulation and tablet hardness affect the drug dissolution profile of carvedilol in matrix tablets?

Wet granulation is mostly used process for manufacturing matrix tablets. Compared to the direct compression method, it allows for a better flow and compressibility properties of compression mixtures. Granulation, including process parameters and tableting, can influence critical quality attributes (CQAs) of hydrophilic matrix tablets. One of the most important CQAs is the drug release profile. We studied the influence of granulation process parameters (type of nozzle and water quantity used as granulation liquid) and tablet hardness on the drug release profile. Matrix tablets contained HPMC K4M hydrophilic matrix former and carvedilol as a model drug. The influence of selected HPMC characteristics on the drug release profile was also evaluated using two additional HPMC batches. For statistical evaluation, partial least square (PLS) models were generated for each time point of the drug release profile using the same number of latent factors. In this way, it was possible to evaluate how the importance of factors influencing drug dissolution changes in dependence on time throughout the drug release profile. The results of statistical evaluation show that the granulation process parameters (granulation liquid quantity and type of nozzle) and tablet hardness significantly influence the release profile. On the other hand, the influence of HPMC characteristics is negligible in comparison to the other factors studied. Using a higher granulation liquid quantity and the standard nozzle type results in larger granules with a higher density and lower porosity, which leads to a slower drug release profile. Lower tablet hardness also slows down the release profile.     

Ramizol® encapsulation into extended release PLGA micro- and nanoparticle systems for subcutaneous and intramuscular administration: in vitro and in vivo evaluation

Objective: Novel antibiotic Ramizol^® is advancing to clinical trials for the treatment of gastrointestinal Clostridium difficile associated disease. Despite this, previous studies have shown a rapid plasma clearance upon intravenous administration and low oral bioavailability indicating pure drug is unsuitable for systemic infection treatment following oral dosing. The current study aims to investigate the development of poly-lactic-(co-glycolic) acid (PLGA) particles to overcome this limitation and increase the systemic half-life following subcutaneous and intramuscular dosing.

Significance: The development of new antibiotic treatments will help in combatting the rising incidence of antimicrobial resistance.

Methods: Ramizol^® was encapsulated into PLGA nano and microparticles using nanoprecipitation and emulsification solvent evaporation techniques. Formulations were analyzed for particle size, loading level and encapsulation efficiency as well as in vitro drug release profiles. Final formulation was advanced to in vivo pharmacokinetic studies in Sprague–Dawley rats.

Results: Formulation technique showed major influence on particle size and loading levels with optimal loading of 9.4% and encapsulation efficiency of 92.06%, observed using emulsification solvent evaporation. Differences in formulation technique were also linked with subsequent differences in release profiles. Pharmacokinetic studies in Sprague–Dawley rats confirmed extended absorption and enhanced bioavailability following subcutaneous and intramuscular dosing with up to an 8-fold increase in T_max and T_1/2 when compared to the oral and IV routes.

Conclusions: Subcutaneous and intramuscular dosing of PLGA particles successfully increased systemic half-life and bioavailability of Ramizol^®. This formulation will allow further development of Ramizol^® for systemic infection eradication.     

Nextel™ 610 alumina fibre reinforced aluminium: influence of matrix and process on flow stress

Continuous alumina fibre reinforced aluminium matrix composites are produced using two different liquid metal infiltration methods, namely direct squeeze casting and gas pressure infiltration. Net-shape fibre performs for longitudinal parallel tensile bars are prepared by winding the Nextel™ 610 alumina fibre (3M, St Paul, MN) into graphite moulds. High purity aluminium, two binary (Al–6% Zn and Al–1% Mg) and one ternary (Al–6% Zn–0.5% Mg) aluminium alloys are used as matrix materials. The composite is tested in uniaxial tension–compression, using unload–reload loops to monitor the evolution of Young's modulus. A linear dependence between Young's modulus and strain is observed; this is attributed, by deduction, to intrinsic elastic non-linearity of the alumina fibre. This conclusion is then used to compare on the basis of the in situ matrix flow curve the influence of matrix composition and infiltration process on the composite stress–strain behaviour.     

The influence of lithium fluoride on in vitro biocompatibility and bioactivity of calcium aluminate–PMMA composite cement

The objective of this study is to assess the influence of lithium fluoride on in vitro biocompatibility and bioactivity of calcium aluminate (CA)-polymethylmethacrylate (PMMA) composite cement exhibiting quick setting time ( < 15 min), low exothermic temperature (< 47 degrees C), and high compressive strength (> 100 MPa). The biocompatibility was measured by examining cytotoxicity tests such as the agar diffusion test with L929 cell line and the hemolysis test with fresh rabbit blood. To estimate the bioactivity of CA-PMMA composite cement, we determined hydroxyapatite (HAp) formation on the surface of composite cement in the simulated body (SBF) solution by using thin-film XRD, XPS, SEM, EPMA and ICP-AES. The results of biocompatibility tests indicated that all experimental compositions of this study had no cytotoxicity and no hemolysis so that there was no cytotoxicity with regard to non-reacted monomers (MMA and TEGDMA) and lithium fluoride. The results of bioactivity tests revealed that CA-PMMA composite cement without lithium fluoride did not form HAp on its surface after 60 days of soaking in the SBF. On the other hand, LiAl2(OH)7 . 2H2O and HAp were formed on the surface of CA-PMMA composite cement including 1.0% by weight of lithium fluoride after 7 and 15 days of soaking in the SBF, respectively. The 5 microm of LiAl2(OH)7 . 2H2O and HAp mixed layers were formed on the surface of specimen after 60 days of soaking in the SBF.     

Sustained-release of Cyclosporin A pellets: preparation,in vitro release,pharmacokinetic studies and in vitro–in vivo correlation in beagle dogs

The aim of this study was to develop Cyclosporin A (CsA) sustained-release pellets which could maintain CsA blood concentration within the therapeutic window throughout dosing interval and to investigate the in vitro–in vivo correlation (IVIVC) in beagle dogs. The CsA sustained-release pellets (CsA pellets) were prepared by a double coating method and characterized in vitro as well as in vivo. Consequently, the CsA pellets obtained were spherical in shape, with a desirable drug loading (7.18?±?0.17?g/100?g), good stability and showed a sustained-release effect. The C_max, T_max and AUC_0–24 of CsA pellets from the in vivo pharmacokinetics evaluation was 268.22?±?15.99?ng/ml, 6?±?0?h and 3205.00?±?149.55?ng·h/ml, respectively. Compared with Neoral®, CsA pellets significantly prolonged the duration of action, reduced the peak blood concentration and could maintain a relatively high concentration level till 24?h. The relative bioavailability of CsA pellets was 125.68?±?5.37% that of Neoral®. Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the pellets. In conclusion, CsA pellets which could ensure a constant systemic blood concentration within the therapeutic window for 24?h were prepared successfully. Meanwhile, this formulation possessed a good IVIVC.     

A microemulsion of puerarin–phospholipid complex for improving bioavailability: preparation,in vitro and in vivo evaluations

Puerarin is a phytochemical with various pharmacological effects, but poor water solubility and low oral bioavailability limited usage of puerarin. The purpose of this study was to develop a new microemulsion (ME) based on phospholipid complex technique to improve the oral bioavailability of puerarin. Puerarin phospholipid complex (PPC) was prepared by a solvent evaporation method and was characterized by X-ray diffraction and infrared spectroscopy. Pseudo-ternary phase diagrams were constructed to investigate the effects of different oil on the emulsifying performance of the blank ME. Intestinal mucosal injury test was conducted to evaluate safety of PPC-ME, and no sign of damage on duodenum, jejunum and ileum of rats was observed using hematoxylin-eosin staining. In pharmacokinetic study of PPC-ME, a significantly greater C_max (1.33?µg/mL) was observed when compared to puerarin (C_max 0.55?µg/mL) or PPC (C_max 0.70?µg/mL); the relative oral bioavailability of PPC-ME was 3.16-fold higher than puerarin. In conclusion, the ME combined with the phospholipid complex technique was a promising strategy to enhance the oral bioavailability of puerarin.     

Development and comparative evaluation of in vitro,in vivo properties of novel controlled release compositions of paroxetine hydrochloride hemihydrate as against Geomatrix™ platform technology

The objective of this study is to develop, in vitro and in vivo evaluation of novel approaches for controlled release of paroxetine hydrochloride hemihydrate (PHH) in comparison to patented formulation PAXIL CR^® tablets of GlaxoSmithKline (Geomatrix? technology). In one of the approaches, hydrophilic core matrix tablets containing 85% of the dose were prepared and further coated with methacrylic acid copolymer to delay the release. An immediate release coating of 15% was given as top coat. The tablets were further optionally coated using ethyl cellulose. In the second approach, hydrophobic matrix core tablets containing metharylic acid copolymer were prepared. In the third approach, PHH was granulated with enteric polymer and further hydrophobic matrix core tablets were prepared. The effect of polymer concentration, level of enteric coating on drug release was evaluated by in vitro dissolution study by varying dissolution apparatus and the rotation speeds. It was found that increase in concentration of high viscosity hydroxypropylmethylcellulose (HPMC) resulted in reduction of the release rate. The drug release was observed to be dependent on the level of enteric coating and ethyl cellulose coating, being slower at increased coating. The release mechanism of PHH followed zero-order shifting to dissolution dependent by the increase of HPMC content. The formulation was stable without change in drug release rate. In vivo study in human volunteers confirmed the similarity between test and innovator formulations. In conclusion, HPMC-based matrix tablets, which were further coated using methacrylic acid copolymer, were found to be suitable for the formulation of single layer-controlled release PHH.     

Thermoresponsive ophthalmic poloxamer/tween/carbopol in situ gels of a poorly water-soluble drug fluconazole: preparation and in vitro–in vivo evaluation

The purpose of the present study was to optimize the formulations of the thermoresponsive ophthalmic in situ gels of a poorly water-soluble drug fluconazole (FLU) and evaluate the in vitro and in vivo properties of the formulations. The thermoresponsive ophthalmic FLU in situ gels were prepared by mixing FLU, Poloxamer407, Tween80, benzalkonium chloride and carbopol934 in borate buffer solution. The in vivo eye irritation tests and ophthalmic absorption were carried out in rabbits. The formulation compositions influenced the physicochemical properties of FLU in situ gels. The amount of poloxamer407 in the formulation was the main factor that affected the sol–gel transition temperature of the products. Tween80 not only improved the solubility of the FLU but also affected the products’ sol–gel transition temperature. In this study, sol–gel transition temperature was not affected by carbopol934. However, carbopol934 affected pH value, transparency and gelling capacity of the products. The product of the optimized formulation was a pseudoplastic fluid and its sol–gel transition temperature was 30.6?±?1.2?°C. The autoclaving test showed that the sol–gel transition temperature, the flow ability and the flow behavior of the test samples did not change obviously after autoclaving sterilization at 121?°C and 15?psi for 20?min, thus the autoclaving was an acceptable sterilization method for this preparation. The thermoresponsive ophthalmic FLU in situ gels’ in vivo ophthalmic absorption was superior to the conventional FLU eye drop. In conclusion, the thermoresponsive ophthalmic FLU in situ gel is a better alternative than the FLU eye drop.     

An in vitro release study of indomethacin from nanoparticles based on methyl methacrylate/glycidyl methacrylate copolymers

Indomethacin was coupled onto some macromolecular nanostructures based on methyl methacrylate copolymers with glycidyl methacrylate and tested as a model drug. The polymeric matrices were synthesized by radical emulsion copolymerization with and without the presence of a continuous external magnetic field of 1500 Gs intensity. Mathematical analysis of the release data was performed using Higuchi, Peppas–Korsmeyer equations. NIR chemical imaging (NIR-CI) was used to provide information about the spatial distribution of the components in the studied nanostructures. This opportunity was used to visualize the spatial distribution of bioactive substances (indomethacin) into the polymeric matrix, as well as to evaluate the degree of chemical and/or physical heterogeneity of the bioactive samples. The release rate dependence on the synthesis conditions as well as on the chemical compositions of the tested polymeric systems, it was also evidenced.     

Vibrational and thermal study on the in vitro and in vivo degradation of a bioabsorbable periodontal membrane: Vicryl® Periodontal Mesh (Polyglactin 910)

Fourier transform Raman (FT-Raman), attenuated total reflection/Fourier transform infrared (ATR/FT-IR) spectra and differential scanning calorimetry (DSC) measurements were performed on a biodegradable periodontal membrane, the Vicryl® periodontal mesh, in order to study its in vitro and in vivo degradation mechanism and kinetics. The hydrolitic in vitro degradation was investigated in two aqueous media: a saline phosphate buffer (SPB, pH=7.4) and a 0.01 M NaOH solution. Moreover, a membrane implanted in vivo for 4 weeks for treatment of contiguous vertical bony defects, was examined. Vibrational and thermal measurements show that the Vicryl® membrane presents a semicrystalline structure. It degrades faster in the NaOH solution than in the SPB and degradation occurs heterogeneously with a progressive increase in the percentage of crystallinity and shortening of the polymeric chains both in vitro and in vivo. The trends of % weight loss and IR I₆₂₇/I₁₄₁₅ intensity ratio (identified as a marker of crystallinity) are discussed in comparison with the DSC results. The IR I₆₂₇/I₁₄₁₅ intensity ratio and X_c% allow to determine the % weight loss undergone by the membrane degraded in vivo. The result obtained shows that the Vicryl® membrane degrades faster in vivo than in vitro with the formation of oligomers which are more easily absorbed by the surrounding tissues than they are soluble in the degradation media examined.     

In vitro and in vivo evaluation of the effects of demineralized bone matrix or calcium sulfate addition to polycaprolactone–bioglass composites

The objective of this study was to improve the efficacy of polycaprolactone/bioglass (PCL/BG) bone substitute using demineralized bone matrix (DBM) or calcium sulfate (CS) as a third component. Composite discs involving either DBM or CS were prepared by compression moulding. Bioactivity of discs was evaluated by energy dispersive X-ray spectroscopy (ESCA) and scanning electron microscopy (SEM) following simulated body fluid incubation. The closest Calcium/Phosphate ratio to that of hydroxyl carbonate apatite crystals was observed for PCL/BG/DBM group (1.53) after 15 day incubation. Addition of fillers increased microhardness and compressive modulus of discs. However, after 4 and 6-week PBS incubations, PCL/BG/DBM discs showed significant decrease in modulus (from 266.23 to 54.04 and 33.45 MPa, respectively) in parallel with its highest water uptakes (36.3 and 34.7%). Discs preserved their integrity with only considerable weight loss (7.5–14.5%) in PCL/BG/DBM group. In vitro cytotoxicity tests showed that all discs were biocompatible. Composites were implanted to defects on rabbit humeri. After 7 weeks, new tissue formation and mineralization at bone-implant interface were observed for all implants. Bone mineral densities at interface were higher than that of implant site and negative controls (defects left empty) but lower than healthy bone level. However, microhardness of implant sites was higher than in vitro results indicating in vivo mineralization of implants. Addition of DBM or CS resulted with higher microhardness values at interface region (ca. 650 μm from implant) compared to PCL/BG and negative control. Histological studies revealed that addition of DBM enhanced bone formation around and into implant while CS provided cartilage tissue formation around the implant. From these results, addition of DBM or CS could be suggested to improve bone healing efficacy of PCL/BG composites.     

Development and evaluation of a novel drug delivery: Soluplus®/TPGS mixed micelles loaded with piperine in vitro and in vivo

Background: Although piperine can inhibit cells of tumors, the poor water solubility restricted its clinical application. This paper aimed to develop mixed micelles based on Soluplus^® and D-α-tocopherol polyethylene glycol succinate (TPGS) to improve the aqueous solubility and anti-cancer effect.

Methods: Piperine-loaded mixed micelles were prepared using a thin-film hydration method, and their physicochemical properties were characterized. The cellular uptake of the micelles was confirmed by confocal laser scanning microscopy in A549 lung cancer cells and HepG₂ liver cancer cells. In addition, cytotoxicity of the piperine mixed micelles was studied in A549 lung cancer cells and HepG₂ liver cancer cells. Free piperine or piperine-loaded Soluplus^®/TPGS mixed micelles were administered at an equivalent dose of piperine at 3.2?mg/kg via a single intravenous injection in the tail vain for the pharmacokinetic study in vivo.

Results: The diameter of piperine-loaded Soluplus^®/TPGS (4:1) mixed micelles was about 61.9?nm and the zeta potential –1.16?±?1.06?mV with 90.9% of drug encapsulation efficiency and 4.67% of drug-loading efficiency. Differential scanning calorimetry (DSC) studies confirmed that piperine is encapsulated by the Soluplus^®/TPGS. The release results in vitro showed that the piperine-loaded Soluplus^®/TPGS mixed micelles presented sustained release behavior compared to the free piperine. The mixed micelles exhibited better antitumor efficacy compared to free piperine and physical mixture against in A549 and HepG₂ cells by MTT assay. The pharmacokinetic study revealed that the AUC of piperine-loaded mixed micelles was 2.56 times higher than that of piperine and the MRT for piperine-loaded mixed micelles was 1.2-fold higher than piperine (p?Conclusion: The results of the study suggested that the piperine-loaded mixed micelles developed might be a potential nano-drug delivery system for cancer chemotherapy. These results demonstrated that piperine-loaded Soluplus^®/TPGS mixed micelles are an effective strategy to deliver piperine for cancer therapy.     

Comparison of cefpodoxime proxetil release and antimicrobial activity from tablet formulations: complexation with hydroxypropyl-β-cyclodextrin in the presence of water soluble polymer

This study aims to prove the complexation of cefpodoxime proxetil (CP) by hydroxypropyl-β-cyclodextrin (HP-β-CD) in the presence of sodium carboxymethyl cellulose (Na CMC), and makes a comparison of commercial tablets by dissolution and antimicrobial activity studies. The CP--HP-β-CD complex was prepared by kneading method and characterized by SEM, FTIR and DSC. The solubility method was used to investigate the effect of HP-β-CD and Na CMC on the solubility of CP. The complex tablets were prepared using direct compression method. Dissolution studies were performed with complex tablets and commercial tablets in pH 1.2, 4.5, 6.8 and 7.4 buffer solutions. It was observed that complexation occurred in all formulations, and HP-β-CD is able to increase CP solubility and dissolution rate of CP was improved from complex tablets, when compared with commercial tablets. Furthermore, the antimicrobial activity studies revealed that the CP--HP-β-CD complex and complex tablets were shown to have more effective antimicrobial activity than commercial tablets. It is evident from the results that complexation with HP-β-CD in the presence of Na CMC is feasible way to prepare a more efficient tablet formulation with improved dissolution and antimicrobial activity.     

In vitro release dynamics of model drugs from psyllium and acrylic acid based hydrogels for the use in colon specific drug delivery

Psyllium is medicinally important gel forming polysaccharides. Keeping in view, the pharmacological importance of psyllium and drug delivery devices based on hydrogels, psyllium, if suitably tailored to prepare the hydrogels, can act as the double potential candidates for the novel drug delivery systems. Therefore, it is an attempt to prepared psyllium and acrylic acid based pH sensitive novel hydrogels by using N,N'-methylenebisacrylamide (N,N-MBAAm) as crosslinker and ammonium persulfate (APS) as initiator for the use in colon specific drug delivery. The present paper discusses the swelling kinetics of the hydrogels and release dynamics of model drugs (tetracycline hydrochloride, insulin and tyrosine) from drug-loaded hydrogels, for the evaluation of the swelling mechanism and drug release mechanism from the polymeric networks .The effect of pH on the swelling kinetics and release pattern of drugs have been studied by varying the pH of the release medium. It has been observed that swelling and release of drugs from the hydrogels occurred through non-Fickian or anomalous diffusion mechanism in distilled water and pH 7.4 buffer. It shows that the rate of polymer chain relaxation and the rate of drug diffusion from these hydrogels are comparable.     

Innovation of novel ‘Tab in Tab’ system for release modulation of milnacipran HCl: optimization,formulation and in vitro investigations

The study was aimed toward development of modified release oral drug delivery system for highly water soluble drug, Milnacipran HCl (MH). Novel Tablet in Tablet system (TITs) comprising immediate and extended release dose of MH in different parts was fabricated. The outer shell was composed of admixture of MH, lactose and novel herbal disintegrant obtained from seeds of Lepidium sativum. In the inner core, MH was matrixed with blend of hydrophilic (Benecel^®) and hydrophobic (Compritol^®) polymers. 3² full factorial design and an artificial neuron network (ANN) were employed for correlating effect of independent variables on dependent variables. The TITs were characterized for pharmacopoeial specifications, in vitro drug release, SEM, drug release kinetics and FTIR study. The release pattern of MH from batch A10 containing 25.17% w/w Benecel^® and 8.21% w/w of Compritol^® exhibited drug release pattern close proximal to the ideal theoretical profile (t_50% = 5.92?h, t_75% = 11.9?h, t_90% = 18.11 h). The phenomenon of drug release was further explained by concept of percolation and the role of Benecel^® and Compritol^® in drug release retardation was studied. The normalized error obtained from ANN was less, compared with the multiple regression analysis, and exhibits the higher accuracy in prediction. The results of short-term stability study revealed stable chataracteristics of TITs. SEM study of TITs at different dissolution time points confirmed both diffusion and erosion mechanisms to be operative during drug release from the batch A10. Novel TITs can be a succesful once a day delivery system for highly water soluble drugs.     

Development of an osmotically-driven pellet coated with acrylic copolymers (Eudragit® RS 30 D) for the sustained release of oxymatrine,a freely water soluble drug used to treat stress ulcers (I): in vitro and in vivo evaluation in rabbits

Purpose: To develop an osmotically-driven pellet coated with polymeric film for sustained release of oxymatrine (OMT), a freely water soluble drug.

Methods: Pellet containing OMT and sodium chloride (NaCl), an osmotically active agent, were prepared by extrusion/spheronization and then coated with acrylic copolymers (Eudragit^® RS 30 D) by the fluidized bed coating process. In vitro release and swelling behavior studies were employed to optimize and to evaluate the sustained-release behavior from the osmotically-driven pellets with film coated. Finally, in vivo evaluation in rabbits was employed to investigate the sustained plasma level of OMT and its active metabolite matrine.

Results: It was found that the F3 formulation, prepared with 20% NaCl and an 8% coating level, showed a continuous NaCl-induced water influx into the pellets providing a gradual sustained release of OMT for over 12?h. Finally, we confirmed that oral OMT with sustained release led to a gradual sustained plasma profile of both OMT, with a reduction in its bioavailability, and MT with an increase in the bioavailability compared with that of oral OMT with immediate release. Conclusions: The pharmaceutical parameters obtained suggested the potential usefulness of oral OMT with sustained release for the treatment of stress ulcers, as well as reducing the risk of MT-induced side effects.