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1.
Int J Pharm ; 661: 124396, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38944168

ABSTRACT

Increasing the solubility of drugs is a recurrent objective of pharmaceutical research, and one of the most widespread strategies today is the formulation of nanocrystals (NCs). Beyond the many advantages of formulating NCs, their incorporation into solid dosage forms remains a challenge that limits their use. In this work, we set out to load Atorvastatin NCs (ATV-NCs) in a delivery device by combining 3D scaffolds with an "in situ" loading method such as freeze-drying. When comparing two infill patterns for the scaffolds at two different percentages, the one with the highest NCs load was chosen (Gyroid 20 % infill pattern, 13.8 ± 0.5 mg). Colloidal stability studies of NCs suggest instability in acidic media, and therefore, the system is postulated for use as a sublingual device, potentially bypassing stomach and hepatic first-pass effects. An ad hoc dissolution device was developed to mimic the release of actives. The nanometric size and properties acquired in the process were maintained, mainly in the dissolution rate and speed, achieving 100 % dissolution of the content in 180 s. Based on these results, the proof of concept represents an innovative approach to converting NCs suspensions into solid dosage forms.

2.
Int J Pharm ; 650: 123720, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38110014

ABSTRACT

Atorvastatin (ATV) is a first-line drug for the treatment of hyperlipidemia. This drug presents biopharmaceutical problems, partly due to its low solubility and dissolution rate. In this work, nanocrystals of ATV stabilized with Tween 80® were designed by wet milling. A full factorial design was applied to optimize the process. Additionally, a cryoprotectant agent (maltodextrin, MTX) was identified, which allowed maintaining the properties of the nanocrystals after lyophilization. The storage stability of the nanocrystals was demonstrated for six months in different conditions. The obtained nanocrystal powder was characterized using SEM, EDXS, TEM, DSC, TGA, FT-IR, and XRD, showing the presence of irregular crystals with semi-amorphous characteristics, likely due to the particle collision process. Based on the reduction in particle size and the decrease in drug crystallinity, a significant increase in water and phosphate buffer (pH 6.8) solubility by 4 and 6 times, respectively, was observed. On the other hand, a noticeable increase in the dissolution rate was observed, with 90 % of the drug dissolved within 60 min of study, compared to 30 % of the drug dissolved within 12 h in the case of the untreated drug or the physical mixture of components. Based on these results, it can be concluded that the nano-milling of Atorvastatin stabilized with Tween 80® is a promising strategy for developing new formulations with improved biopharmaceutical properties of this widely used drug.


Subject(s)
Biological Products , Nanoparticles , Polysorbates , Atorvastatin/chemistry , Spectroscopy, Fourier Transform Infrared , Solubility , Nanoparticles/chemistry , Freeze Drying , Particle Size
3.
Disaster Med Public Health Prep ; 16(5): 1935-1941, 2022 10.
Article in English | MEDLINE | ID: mdl-33762042

ABSTRACT

OBJECTIVE: In this work, in order to establish a better comprehension of the association between Argentina and its neighbor countries' capacity, and COVID-19 burden during the first 3 months, different indicators were evaluated. METHOD: We analyzed the association between GHSI, INFORM index and COVID-19 burden (number of confirmed cases and deaths), also the number of tests, lethality and the stringency of Governmental policies were evaluated. RESULTS: Uruguay, Paraguay, and Bolivia started earlier different prevention measures. The number of tests differs, as Chile is the 1 that makes more. Uruguay and Paraguay register fewer positive cases and deaths from COVID-19. The GHS index is led by Brazil, followed by Argentina, and then Chile. However, the INFORM index is led by Uruguay followed by Argentina, while Chile and Paraguay are on par. CONCLUSION: The countries that took preventive measures earlier and carried out a more tests are the ones that are obtaining the best results against COVID-19.


Subject(s)
COVID-19 , Pandemics , Humans , Pandemics/prevention & control , COVID-19/epidemiology , Argentina/epidemiology , Uruguay/epidemiology , Chile
4.
Eur J Pharm Sci ; 160: 105748, 2021 May 01.
Article in English | MEDLINE | ID: mdl-33567324

ABSTRACT

Glaucoma is a degenerative optic neuropathy characterized by increased intraocular pressure that if untreated can result in blindness. Ophthalmological drug therapy is a challenge of great clinical importance due to the diversity of ocular biological barriers which commonly causes limited or no effectiveness for drugs delivered through the eye. In this work, we proposed the development of nanosized cubic liquid crystals (cubosomes) as a new drug carrier system for latanoprost, an anti-glaucoma drug. Latanoprost-loaded phytantriol cubosomes (CubLnp) were prepared using a top-down method. Latanoprost concentration in the formulations ranged from 0.00125% to 0.02% w/v. All cubosomes displayed an average size around 200 nm, a low polydispersity index of 0.1 and zeta potential values around -25 mV, with an encapsulation efficiency of about 90%. Structural studies revealed that cubosomes displayed a double-diamond surface, Pn3m cubic-phase structure, and was not affected by drug loading. Calorimetric studies revealed a fast and exothermic interaction between latanoprost and cubosomes. According to in vitro essays, latanoprost release from cubosomes was slow in time, evidencing a sustained release profile. Based on this behavior, the in vivo hypotensive intraocular effect was evaluated by means of the subconjunctival administration of CubLnp in normotensive rabbits. We obtained promising results in comparison with a marketed latanoprost formulation (0.005% w/v).


Subject(s)
Glaucoma , Animals , Drug Carriers/therapeutic use , Fatty Alcohols , Glaucoma/drug therapy , Latanoprost/therapeutic use , Rabbits
5.
Front Immunol ; 11: 2087, 2020.
Article in English | MEDLINE | ID: mdl-33193292

ABSTRACT

Fasciola hepatica is helminth parasite found around the world that causes fasciolosis, a chronic disease affecting mainly cattle, sheep, and occasionally humans. Triclabendazole is the drug of choice to treat this parasite. However, the continuous use of this drug has led to the development of parasite resistance and, consequently, the limitation of its effectiveness. Hence, vaccination appears as an attractive option to develop. In this work, we evaluated the potential of F. hepatica Kunitz-type molecule (FhKTM) as an antigen formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate ester (Coa-ASC16) and the synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) during an experimental model of fasciolosis in mice, and we further dissected the immune response associated with host protection. Our results showed that immunization of mice with FhKTM/CpG-ODN/Coa-ASC16 induces protection against F. hepatica challenge by preventing liver damage and improving survival after F. hepatica infection. FhKTM/CpG-ODN/Coa-ASC16-immunized mice elicited potent IFN-γ and IL-17A with high levels of antigen-specific IgG1, IgG2a, and IgA serum antibodies. Strikingly, IL-17A blockade during infection decreased IgG2a and IgA antibody levels as well as IFN-γ production, leading to an increase in mortality of vaccinated mice. The present study highlights the potential of a new vaccine formulation to improve control and help the eradication of F. hepatica infection, with potential applications for natural hosts such as cattle and sheep.


Subject(s)
Antibodies, Helminth/immunology , Fasciola hepatica/immunology , Fascioliasis/prevention & control , Helminth Proteins/pharmacology , Interferon-gamma/immunology , Interleukin-17/immunology , Vaccines/pharmacology , Animals , Fascioliasis/immunology , Female , Helminth Proteins/immunology , Mice , Mice, Inbred BALB C , Vaccines/immunology
6.
Pharmacol Rep ; 71(5): 794-797, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31377560

ABSTRACT

BACKGROUND: The aim of this work was evaluate the antioxidant effect of ascorbyl laurate (ASC12) based nanostructures applied topically to the cornea of ocular normotensive and hypertensive rabbits. The ASC12 was chosen for its capacity to form liquid lyotropic crystal and keeps its free radical trapping power. METHODS: The hypertension model was performed in six rabbits and was obtained by the application of intracameral injections of alpha-chymotrypsin in the right eye. A single 50 ml dose of ascorbyl laurate coagel 2% w/v (COA-ASC12) was applied topically to the cornea of six normotensive and six hypertensive rabbits. The aqueous humor samples were obtained before and after instillation of COA-ASC12 at different times (2 h and 4 h). Antioxidant capacity was determined via the reduction reaction with iron and tripyridyltriazine (FRAP) and the total proteins were measured using the Bradford reagent. RESULTS: The kinetic antioxidant capacity in the aqueous humor of normotensive and hypertensive rabbits showed a maxim increment at 4 h instillation. Also, the antioxidant capacity in the aqueous humor of hypertensive rabbits was ten times lower than in normotensive rabbits. CONCLUSION: This type of nanostructures has the potential to significantly improve the topical formulation for the prophylaxis and treatment of several eye diseases.


Subject(s)
Antioxidants/pharmacology , Aqueous Humor/drug effects , Ascorbic Acid/analogs & derivatives , Intraocular Pressure/drug effects , Nanostructures/chemistry , Ocular Hypertension/drug therapy , Administration, Ophthalmic , Animals , Antioxidants/administration & dosage , Antioxidants/chemistry , Antioxidants/pharmacokinetics , Aqueous Humor/metabolism , Ascorbic Acid/administration & dosage , Ascorbic Acid/chemistry , Ascorbic Acid/pharmacokinetics , Ascorbic Acid/pharmacology , Disease Models, Animal , Gels , Ocular Hypertension/metabolism , Rabbits
7.
J Food Sci ; 84(6): 1529-1537, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31131890

ABSTRACT

This study aims to assess the enhancement of the chemical and sensory properties of roasted peanuts during storage, through the application of high-protein defatted peanut flour (DPF) coatings incorporated with and without antioxidants. The control sample without coating, packed in normal atmosphere (control), showed the highest conjugated dienes (CD) increment (from 1.17 on day 0 to 3.60 on day 180). Roasted peanuts without coating, packed in high barrier bags under vacuum, reached the lowest CD at day 180 (1.92). Conjugated trienes and peroxide values were analogous to CD. The control exhibited the greatest decrease in α-tocopherol (from 27.65 mg/100 g on day 0 to 21.32 mg/100 g on day 180) and γ-tocopherol (from 21.91 mg/100 g on day 0 to 14.99 mg/100 g on day 180). 3-Methylpyridine and 2,5-dimethylpyrazine decreased with storage time only for the control, which had the highest increase in oxidized flavor (from 0 on day 0 to 13.30 on day 180), cardboard (from 7.67 on day 0 to 15.23 on day 180), and astringency. The lowest decreases in roasted peanutty scores were seen in coated samples. DPF coatings delayed roasted peanuts oxidation, enhancing their sensory properties and shelf life compared with the control sample. PRACTICAL APPLICATION: Defatted peanut flour (DPF) is a byproduct obtained during peanut oil extraction and is a possible material for edible film preparation. This strategy adds value to the peanut industry by transforming a by-product into a material with the potential to develop biodegradable and economical films. The application of this DPF-based edible coating on the surface of roasted peanuts may have contributed to extent product's shelf life, allowing for coated products to be packaged in lower barrier and less expensive materials. Use of peanut material to coat peanuts avoids the risk of allergen protein cross contamination, which would be highly valuable for the food industry.


Subject(s)
Arachis/chemistry , Cooking/methods , Seeds/chemistry , Antioxidants/chemistry , Hot Temperature , Humans , Oxidation-Reduction , Peroxides/analysis , Taste , alpha-Tocopherol/analysis
8.
Life Sci ; 218: 233-240, 2019 Feb 01.
Article in English | MEDLINE | ID: mdl-30605647

ABSTRACT

Oxidative stress triggers ocular neurodegenerative diseases, such as glaucoma or macular degeneration. The increase of reactive oxygen and nitrogen species in retinal ganglion cells (RGCs) causes damage to the structure and function of the axons that make up the optic nerve, leading to cell death arising from apoptosis, necrosis or autophagy in the RCGs. The use of antioxidants to prevent visual neurodegenerative pathologies is a novel and possibly valuable therapeutic strategy. To investigate in vitro and in vivo neuroprotective efficacy of melatonin (MEL) in RGCs, we used a model of oxidative glutamate (GLUT) toxicity in combination with l-butionin-S, R-sulfoximine (BSO), which induces cell death by apoptosis through cytotoxicity and oxidative stress mechanisms. Histological sectioning and immunohistochemical assays using the TUNEL technique were performed to determine the damage generated in affected cells and to observe the death process of RGCs. Whit BSO-GLUT the results revealed a progressive RGCs death without any significant evidence of a decreased retinal function after 9 days of treatment. In this way, we were able to develop a retinal degeneration model in vivo to carry out treatment with MEL and observed an increase in the survival percentage of RGCs, showing that BSO-GLUT could not exert an oxidant effect on cells to counteract the effect of MEL. These findings reveal that MEL has a neuroprotective and antiapoptotic effect as evidenced by the reduction of oxidative stress damage. MEL demonstrated in this model makes it a promising neuroprotective agent for the treatment of ocular neurodegenerative diseases when administered locally.


Subject(s)
Melatonin/pharmacology , Neuroprotection/drug effects , Neuroprotective Agents/pharmacology , Retinal Degeneration/drug therapy , Retinal Ganglion Cells/drug effects , Animals , Apoptosis , Cell Proliferation , Cells, Cultured , Chick Embryo , Glutamic Acid/pharmacology , In Vitro Techniques , Oxidative Stress/drug effects , Rabbits , Retinal Degeneration/metabolism , Retinal Degeneration/pathology , Retinal Ganglion Cells/cytology , Retinal Ganglion Cells/metabolism
9.
J Pharm Pharmacol ; 70(1): 51-58, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29034951

ABSTRACT

OBJECTIVES: Here, we aimed to assess the pharmacokinetic performance and therapeutic response (anthelmintic efficacy) of an albendazole (ABZ) nano-sized formulation in dogs. METHODS: In the pharmacokinetic study, ABZ self-dispersible nanocrystals (SDNCS) and a control formulation were administered orally to healthy dogs (n = 6). The concentrations of the sulphoxide metabolite in plasma were determined by high-performance liquid chromatography. For the anthelmintic efficacy trial, SDNCS and a commercially available formulation of ABZ were given to naturally parasitised dogs. The number of Ancylostoma caninum eggs in the faeces was determined using the McMaster technique. KEY FINDINGS: The area under the curve, Tmax and Cmax for the SDNCS were improved compared to the control. The efficacy study showed no statistical differences between the SDNCS and the commercial formulation at the doses of 25 and 12.5 mg/kg. However, significant differences (P < 0.05) between the treatments were found at 6.25 mg/kg (a quarter of the reference dose) with a reduction in the faecal nematode egg counts of 62.0 ± 21.1% and 100 ± 0% for the control and SDNCS, respectively. CONCLUSIONS: The improved pharmacokinetic performance observed for the novel formulation of ABZ correlated with an improved in vivo therapeutic response against a model intestinal nematode parasite in dogs.


Subject(s)
Albendazole/administration & dosage , Ancylostomiasis/drug therapy , Anthelmintics/administration & dosage , Nanoparticles , Albendazole/pharmacokinetics , Albendazole/pharmacology , Ancylostoma/drug effects , Ancylostomiasis/parasitology , Ancylostomiasis/veterinary , Animals , Anthelmintics/pharmacokinetics , Anthelmintics/pharmacology , Area Under Curve , Chromatography, High Pressure Liquid , Dog Diseases/drug therapy , Dog Diseases/parasitology , Dogs , Dose-Response Relationship, Drug , Feces/parasitology , Female , Male , Treatment Outcome
10.
Vet Immunol Immunopathol ; 178: 50-6, 2016 Oct 01.
Article in English | MEDLINE | ID: mdl-27496742

ABSTRACT

Control of ovine brucellosis with subcellular vaccines can solve some drawbacks associated with the use of Brucella melitensis Rev.1. Previous studies have demonstrated that the polymeric antigen BLSOmp31 administered by parenteral route was immunogenic and conferred significant protection against B. ovis in rams. Immunization with BLSOmp31 by conjunctival route could be efficient for the induction of mucosal and systemic immune responses. In this work, we evaluated the conjunctival immunization using a thermoresponsive and mucoadhesive in situ gel composed of Poloxamer 407 (P407) and chitosan (Ch) as vaccine delivery system for BLSOmp31 in rams. Serum samples, saliva, lacrimal, preputial and nasal secretions were analyzed to measure specific IgG and IgA antibodies. Cellular immune response was evaluated in vivo and in vitro. Immunization with BLSOmp31-P407-Ch induced high IgG antibody levels in serum and preputial secretions which remained at similar levels until the end of the experiment. Levels of IgG in saliva, lacrimal and nasal secretions were also higher compared to unvaccinated control group but decreased more rapidly. IgA antibodies were only detected in nasal and preputial secretions. BLSOmp31-P407-Ch stimulated a significant cellular immune response in vivo and in vitro. The induction of systemic and local immune responses indicates a promising potential of P407-Ch for the delivery of BLSOmp31 by conjunctival route.


Subject(s)
Brucellosis/veterinary , Sheep Diseases/prevention & control , Animals , Antibodies, Bacterial/blood , Bacterial Outer Membrane Proteins/immunology , Brucella Vaccine/administration & dosage , Brucella ovis/immunology , Brucellosis/immunology , Brucellosis/prevention & control , Conjunctiva/immunology , Drug Delivery Systems/methods , Drug Delivery Systems/veterinary , Gels , Immunity, Cellular , Immunity, Mucosal , Male , Sheep , Sheep Diseases/immunology , Vaccination/methods , Vaccination/veterinary , Vaccines, Synthetic/administration & dosage
11.
Curr Pharm Des ; 22(43): 6587-6594, 2016.
Article in English | MEDLINE | ID: mdl-27526793

ABSTRACT

Suramab (SUM) is a new pharmaceutical combination made up of suramine (SUR) and bevacizumab (BVM), which showed a high synergistic effect when administered jointly. As the pharmaceutical vehicle, poloxamer aqueous dispersions were used since this system is able to maintain their fluidity at low temperatures (<15ºC) but which become gel in the corporal environment (>35ºC). In the present study we aimed at evaluating the effect of Poloxamer to prolong the effect of SUM. These formulations were characterized using rheological, biopharmaceutical (drug release) and morphological (SEM) technique. Corneal NV was induced in Sprague Dawley rats Corneal. At 15 days of follow up animals were sacrificed and perfused with black drawing ink. Digital photographs were taken and the area of neovascularisation (ANV) was calculated using the image programmed. The rheological behavior was influenced by the addition of drugs, resulting in a decrease in the gelation temperature (Tsol/gel). Both drugs were released from poloxamer gels by means of an anomalous mechanism. However, BVM was released faster than SUR, with their combination (SUM) to appearing to reduce delivery, probably due to interactions between the drugs or with the polymeric matrix. The in vivo studies showed that SUM-poloxamer gel was able to increase the corneal antiangiogenic effect compared to the SUM solution and BVM alone at 15 days of follow-up. Furthermore no injurious effects were observed in the histological tissue examination after drug administration. The presence of Poloxamer, known to modulate control release of biological agents, seems to have a favorable effect on SUM subconjunctival administered.


Subject(s)
Angiogenesis Inhibitors/administration & dosage , Bevacizumab/administration & dosage , Hydrogels , Suramin/administration & dosage , Administration, Ophthalmic , Animals , Corneal Neovascularization/prevention & control , Drug Combinations , Humans , Rats , Rats, Sprague-Dawley , Temperature
12.
Mater Sci Eng C Mater Biol Appl ; 62: 489-96, 2016 May.
Article in English | MEDLINE | ID: mdl-26952451

ABSTRACT

Previous studies have demonstrated that parenteral immunization with polymeric antigen BLSOmp31 induced a strong immune response and conferred protection against Brucella ovis in rams. This work describes the development of a novel formulation strategy for the delivery of BLSOmp31 in the nasal mucosa. Chitosan microparticles were prepared by spray-drying technology processes and recombinant chimera BLSOmp31 was loaded by passive adsorption onto chitosan microspheres, which were characterized by means of the evaluation of size, zeta potential, morphology, and loading and release rate of BLSOmp31. The mucoadhesive properties of microspheres were evaluated by studying the interaction between microparticles and mucin. The antigen BLSOmp31 integrity was investigated by SDS-PAGE. The yield of production of spray-drying process was 68.95%. Microspheres had a good sphericity, 1-10 µm of particle size and had a positive charge. The loading capacity was found to be 45.19%. The initial fast release of BLSOmp31 from chitosan microparticles was 60%. The BLSOmp31 integrity was not affected by passive adsorption (ionic interaction). The amount of mucin adsorbed on the surface of CMs-BLSOmp31 was lower than on the surface of blank CMs at neutral pH. In vivo studies were carried out in rams. Intranasal immunization induced systemic and local antibodies. In conclusion, the use of BLSOmp31-loaded chitosan spray-drying microspheres offers a promising way for nasal mucosal vaccination in sheep against brucellosis.


Subject(s)
Antigens/immunology , Brucellosis/prevention & control , Chitosan/chemistry , Microspheres , Administration, Intranasal , Adsorption , Animals , Antibodies/blood , Bacterial Proteins/genetics , Bacterial Proteins/immunology , Bacterial Proteins/metabolism , Brucella ovis/metabolism , Brucellosis/microbiology , Brucellosis/veterinary , Chemistry, Pharmaceutical , Drug Carriers/chemistry , Electrophoresis, Polyacrylamide Gel , Microscopy, Atomic Force , Mucins/chemistry , Mucins/metabolism , Particle Size , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/immunology , Sheep , Spectroscopy, Fourier Transform Infrared
13.
J Pharm Sci ; 103(12): 3859-3868, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25294798

ABSTRACT

A novel ophthalmic formulation based on the ionic complexation between Eudragit E 100 (EU) and flurbiprofen (FB) is proposed. The selected complex composition, named EU-FBH50 Cl50 , had the basic groups of EU completely neutralized with equal molar amounts of FB and HCl. This complex, obtained in the solid state, exhibited a high aqueous compatibility producing a colloidal dispersion with a high positive electrokinetic potential, in which more than 99% of FB was ionically condensed with EU. In bicompartimental Franz cells, FB diffusion from the complex was very slow. However, dispersion in 0.9% NaCl increased the FB release through an ionic exchange, providing an optimal constant rate of delivery. Corneal FB permeation from 0.1% EU-FBH50 -Cl50 dispersed in 0.9% NaCl solution was substantially more effective compared with 0.1% FB solution, EU-FBH50 -Cl50 (Dex), or Tolerane(®) (a marketed formulation). This complex formulation was shown to be innocuous for rabbit ocular tissues because no irritant effects were evidenced.


Subject(s)
Cornea/drug effects , Flurbiprofen/administration & dosage , Methylmethacrylates/administration & dosage , Ophthalmic Solutions/administration & dosage , Animals , Biological Availability , Chemistry, Pharmaceutical/methods , Drug Carriers/administration & dosage , Drug Delivery Systems/methods , Drug Stability , Particle Size , Permeability , Rabbits
14.
Sci Pharm ; 80(2): 487-96, 2012.
Article in English | MEDLINE | ID: mdl-22896833

ABSTRACT

Equilibria and release properties of aqueous systems consisting of a set of five non-steroidal anti-inflammatory drugs (AH) complexed with the cationic polymethacrylate Eudragit E 100 (EU) are reported in this study. The composition (EU(AH)(50) (HCl)(50)) having fifty mole percent of each counterion (A(-) and Cl(-)) produces clear, stable aqueous dispersions in which a remarkably high proportion of AH (higher than 98%) is condensed with the PE under the form of ion pairs. This property expands the interval of pH in which AH are aqueous soluble. The set of AH contains members with and without an alpha methyl group (-(CH(3))CH-COOH: Flurbiprofen, Naproxen, Ketoprofen) and (-CH(2)-COOH: Diclofenac, Indomethacin). The proportion of ion pairs in the complexes was lower in the former group. Release of AH from the complexes toward a saline (NaCl 0.9%) solution was assayed in Franz cells. The five complexes behaved as drug carriers that exhibited a slow drug release with a remarkable zero order. In line with the percentages of counterionic condensation observed, release rates from -(CH(3))CH-COOH complexes were clearly higher than those of -CH(2)-COOH ones.

15.
Drug Deliv ; 17(4): 208-13, 2010 May.
Article in English | MEDLINE | ID: mdl-20230248

ABSTRACT

In this work, the design and evaluation of a colonic drug delivery system containing mesalamine (M) is presented. The main goal was to enable M to reach the first part of the colon, where the drug could then be released. To facilitate this, a tablet core was coated with two thin layers. The first compounded by chitosan, which was responsible for core protection in the small intestine until it reached the colon. Once at the colon, microbiological enzymatic activity of the caecal content would degrade the Ch layer, thus triggering drug release. The second layer, the outer one, was compounded with Eudragit L100 (EL), with its function being to avoid the dissolution of the Ch-covered core along the gastro intestinal tract (GIT). In order to achieve a modulated drug release, carbomer P934 (1%) was also included. Dissolution studies showed that the formulation seemed to behave as predicted. The amount of M released from the coated tablet was less than 10% at pH = 1.2 and 6.8. However, when the coated tablet was evaluated in a medium with a caecal content of pH = 7.4, the M delivery was immediately triggered owing to enzymatic activity of the microflora. In this medium, approximately 60% of M was released in a period of 3 h. Although these results are promising, further studies are still necessary to evaluate the possible in vitro/in vivo correlations.


Subject(s)
Acrylates/administration & dosage , Acrylates/pharmacokinetics , Colon/metabolism , Drug Delivery Systems/methods , Drug Design , Mesalamine/administration & dosage , Mesalamine/pharmacokinetics , Polymers/administration & dosage , Polymers/pharmacokinetics , Polymethacrylic Acids/pharmacokinetics , Animals , Colon/drug effects , Male , Polymethacrylic Acids/administration & dosage , Rats , Rats, Wistar
16.
Int J Pharm ; 288(1): 87-99, 2005 Jan 06.
Article in English | MEDLINE | ID: mdl-15607261

ABSTRACT

The objective of the study is to develop and characterize the delivery properties of swellable drug-polyelectrolyte matrices (SDPM). Solid complexes (C-D)X of carbomer (C) neutralized with different proportions of model basic drugs (D), in which D is atenolol, lidocaine, and metoclopramide, and X=25, 50, 75 and 100 mol of D per 100 equivalents of carboxylic groups of C, were prepared and characterized by DSC-TG, IR, and X-ray diffraction studies. Mechanistic studies with hydrophilic and hydrophobic basic drugs were conducted to explore the drug release patterns of SDPM. Besides, release and up-take studies were carried out in water and NaCl solution to examine the influence of ionic effects. The authors concluded that drugs can be loaded in a high proportion on to the polymer and therefore the resulting (C-D) material could be diluted with other polymers to modulate delivery properties of SDPM. Matrices of atenolol and lidocaine exhibited robust delivery properties with regard to change in proportion of loading D.


Subject(s)
Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Delivery Systems/methods , Acrylic Resins/chemistry , Acrylic Resins/pharmacokinetics , Calorimetry, Differential Scanning , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction
17.
Int J Pharm ; 233(1-2): 191-8, 2002 Feb 21.
Article in English | MEDLINE | ID: mdl-11897423

ABSTRACT

A solid pharmaceutical dosage formulation using a novel dry plant extract of Peumus boldus MOL. (Monimiaceae) (Pb) is proposed. The botanical evaluation of plant material, through morphological and anatomical diagnosis, is presented. This evaluation permits to identify the herb to be used correctly. The analysis of the most extractive solvent mixture and the attainment of plant extract (fluid and dry) are reported. Several formulations (tablets) containing a novel dry plant extract of Pb and common excipients for direct compression are evaluated. The following formulation: dry plant extract of Pb (170 mg), Avicel PH101 (112 mg), Lactose CD (112) and magnesium stearate (6 mg), compressed at 1000 mPa, showed the best pharmaceutical performance.


Subject(s)
Monimiaceae/anatomy & histology , Monimiaceae/chemistry , Plant Leaves/anatomy & histology , Plant Leaves/chemistry , Chemistry, Pharmaceutical , Compressive Strength , Hardness , Plant Extracts/chemistry , Plants, Medicinal/anatomy & histology , Plants, Medicinal/chemistry , Powders , Rheology , Tablets
18.
AAPS PharmSciTech ; 3(3): E22, 2002.
Article in English | MEDLINE | ID: mdl-12916937

ABSTRACT

The objective of this work was to design a mucoadhesive tablet with a potential use in the treatment of oral candidosis. A 2-layered tablet containing nystatin was formulated. Lactose CD (direct compression), carbomer (CB), and hydroxypropylmethylcellulose (HPMC) were used as excipients. Tablets were obtained through direct compression. Properties such as in vitro mucoadhesion, water uptake, front movements, and drug release were evaluated. The immediate release layer was made of lactose CD (100 mg) and nystatin (30 mg). The CB:HPMC 9:1 mixture showed the best mucoadhesion properties and was selected as excipient for the mucoadhesive polymeric layer (200 mg). The incorporation of nystatin (33.3 mg) in this layer affected the water uptake, which, in turn, modified the erosion front behavior. Nystatin showed a first-order release. The polymeric layer presented an anomalous kinetic (n = 0.82) when this layer was individually evaluated. The mucoadhesive tablet formulated in this work releases nystatin quickly from the lactose layer and then in a sustained way, during approximately 6 hours, from the polymeric layer. The mixture CB:HPMC 9:1 showed good in vitro mucoadhesion. A swelling-diffusion process modulates the release of nystatin from this layer. A non-Fickian (anomalous) kinetic was observed.


Subject(s)
Methylcellulose/analogs & derivatives , Nystatin/chemistry , Acrylic Resins/chemistry , Acrylic Resins/metabolism , Acrylic Resins/therapeutic use , Adhesiveness , Administration, Oral , Antifungal Agents/chemistry , Antifungal Agents/metabolism , Antifungal Agents/therapeutic use , Candidiasis, Oral/drug therapy , Chemistry, Pharmaceutical , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/metabolism , Delayed-Action Preparations/therapeutic use , Diffusion , Drug Compounding , Drug Design , Drug Evaluation, Preclinical/methods , Hypromellose Derivatives , Lactose/chemistry , Lactose/metabolism , Lactose/therapeutic use , Methylcellulose/chemistry , Methylcellulose/metabolism , Methylcellulose/therapeutic use , Nystatin/metabolism , Nystatin/therapeutic use , Solubility , Tablets , Time Factors , Water/metabolism
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