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1.
Life Sci ; 346: 122629, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38631667

RESUMO

Ferroptosis is a novel type of controlled cell death resulting from an imbalance between oxidative harm and protective mechanisms, demonstrating significant potential in combating cancer. It differs from other forms of cell death, such as apoptosis and necrosis. Molecular therapeutics have hard time playing the long-acting role of ferroptosis induction due to their limited water solubility, low cell targeting capacity, and quick metabolism in vivo. To this end, small molecule inducers based on biological factors have long been used as strategy to induce cell death. Research into ferroptosis and advancements in nanotechnology have led to the discovery that nanomaterials are superior to biological medications in triggering ferroptosis. Nanomaterials derived from iron can enhance ferroptosis induction by directly releasing large quantities of iron and increasing cell ROS levels. Moreover, utilizing nanomaterials to promote programmed cell death minimizes the probability of unfavorable effects induced by mutations in cancer-associated genes such as RAS and TP53. Taken together, this review summarizes the molecular mechanisms involved in ferroptosis along with the classification of ferroptosis induction. It also emphasized the importance of cell organelles in the control of ferroptosis in cancer therapy. The nanomaterials that trigger ferroptosis are categorized and explained. Iron-based and noniron-based nanomaterials with their characterization at the molecular and cellular levels have been explored, which will be useful for inducing ferroptosis that leads to reduced tumor growth. Within this framework, we offer a synopsis, which traverses the well-established mechanism of ferroptosis and offers practical suggestions for the design and therapeutic use of nanomaterials.


Assuntos
Ferroptose , Nanoestruturas , Neoplasias , Ferroptose/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Animais , Simulação de Dinâmica Molecular , Ferro/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
2.
Breast Cancer ; 30(6): 1065-1078, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37695494

RESUMO

BACKGROUND: Allyl isothiocyanate (AITC) is an excellent active phytoconstituent recently revealed for cancer treatment. The strategic prominence of this study was to synthesize and characterize AITC-embedded tripolyphosphate-modified chitosan nanoparticles (AITC@CS-TPP-NPs) by ionic gelation. METHOD: Chitosan is recycled as a polymer to fabricate AITC@CS-TPP-NPs; the fabricated nanoparticles (NPs) are then characterized using FT-IR spectroscopy, DSC, XRD, zeta potential, size analysis, SEM, EDX, entrapment efficiency, in vitro drug release study, and in vitro cytotoxicity activity against MCF-7 to explore the effectiveness and strength. RESULTS: As a result, developed AITC@CS-TPP-NPs demonstrates good stability with a zeta potential of 35.83 mV and 90.14% of drug release. The anticancer potential of AITC@CS-TPP-NPs shows the improved cytotoxicity activity of AITC due to the surface modification of CS using TPP. Hence, the cytotoxicity of AITC@CS-TPP-NPs was tested in vitro against a human breast cancer cell line (MCF-7) and found to be considerable. CONCLUSION: The AITC@CS-TPP-NPs were effectively synthesized and have significant benefits, including being easy to prepare, stable, and affordable with wide use in human breast cancer against cell line (MCF-7).


Assuntos
Neoplasias da Mama , Quitosana , Nanopartículas , Humanos , Feminino , Quitosana/química , Neoplasias da Mama/tratamento farmacológico , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas/química , Isotiocianatos/farmacologia
3.
Mol Cell Biochem ; 478(12): 2763-2777, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36929336

RESUMO

Allyl isothiocyanates (AITC) have gained recognition in recent years as effective chemotherapeutic and epigenetic modulators. The chemopreventive properties and toxicological perspectives of AITCs from the last few decades were taken into account by a number of investigations. Their active therapeutic relevance was hindered by a number of factors, including instability under typical physiological conditions and low bioavailability due to low aqueous solubility. In this review, we highlighted the chemopreventive attributes of AITC in relation to its molecular mechanisms and metabolic fate for cancer. Moreover, we emphasized on investigational anticancer activities and various strategies for delivery of AITC in different types of cancer. Considering cellular interactions, we shed light on the toxicological properties of AITCs to address further issues regarding their assessment in therapeutic development. This review identifies knowledge gaps with various contemporary approaches involving most recent studies and may pave the way for a better understanding for the development of novel AITC therapeutics.


Assuntos
Isotiocianatos , Neoplasias , Humanos , Isotiocianatos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle
4.
Int J Pharm Compd ; 27(1): 60-71, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36720063

RESUMO

The objective of this study was to prepare and evaluate ibuprofen nanocrystals using isopropyl alcohol and stabilizer sodium lauryl sulphate by way of the precipitation method. The nanocrystals were prepared by the bottom-up approach of the precipitation technique. This technique involves the use of an organic phase, which is completely miscible in the external aqueous phase. The ratio used for organic solvent-to-aqueous solvent was 1:50. The Fourier Transform Infrared Spectroscopy analyses confirmed that the drug and excipients were compatible, and the differential scanning calorimetry results indicated that the precipitation method led to no change in the crystalline structure of the drug. Scanning electron microscopy analysis of ibuprofen nanocrystals showed the promising size reduction of pure drug ibuprofen. Differential light scattering technique showed significant decrease in particle size and good stability of ibuprofen nanocrystals. Ibuprofen nanocrystals increased 20% to 25% of the saturation solubility of ibuprofen nanocrystals. Ibuprofen nanocrystals showed 90% drug release in the dissolution medium within 1 hour, while the pure drug and market product were dissolved only up to 58% and 63%, respectively. Ibuprofen nanocrystals increased the saturation solubility and in vitro dissolution of the drug as compared to conventional market product.


Assuntos
Ibuprofeno , Nanopartículas , Ibuprofeno/química , Excipientes/química , Solventes , Água , Solubilidade , Nanopartículas/química , Comprimidos/química
5.
Int J Pharm Compd ; 27(1): 78-87, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36720065

RESUMO

The objective of this study was to prepare agglomerated isomalt by using the melt granulation process. This method involved the use of 99.5% of isomalt with the meltable binder glyceryl monostearate in a concentration of 0.5%. Glyceryl monostearate has a melting point of 50°C to 55°C, therefore, glyceryl monostearate was melted at its melting point and isomalt powder was blended with it to break the mass into agglomerates. The agglomerates were cooled to room temperature and were then screened to obtain granules of the desired size. The Fourier Transform Infrared Spectroscopy studies confirmed that the chemical structure of isomalt was not changed before and after the melt granulation process. A differential scanning calorimetry study showed that there was no appearance of more new peaks or disappearance of  one or more peaks corresponding to those of the isomalt powder and agglomerated isomalt, which showed no changes in the structure of the isomalt powder before and after the agglomeration process. The agglomerated isomalt and galenIQ 721 showed almost identical solubility profiles for g of solute per 100 g of solution at different temperatures. The scanning electron microscopy analysis of agglomerated isomalt showed promising results for the preparation of agglomerates of isomalt with glyceryl monostearate. The flow properties of the agglomerated isomalt compared with the galenIQ 721 and pure isomalt powder and melt granulation process showed promising results for agglomerated isomalt. The melt granulation process showed promising results to prepare agglomerates of the isomalt with the meltable binder glyceryl monostearate.


Assuntos
Dissacarídeos , Excipientes , Pós , Dissacarídeos/química , Excipientes/química , Álcoois Açúcares/química , Solubilidade
6.
Turk J Pharm Sci ; 19(5): 560-571, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36317931

RESUMO

Objectives: This investigation was aimed at designing an effective mucoadhesive microemulsion system to accomplish higher brain uptake of curcumin through intranasal route. Materials and Methods: Mucoadhesive microemulsion of curcumin (MMEC) was developed using screened oil, surfactant, and co-surfactant by Box-Behnken design and was evaluated for mucoadhesion, stability, and naso-ciliotoxicity study. Comparative brain uptake of curcumin after nasal administration of MMEC and polycarbophil curcumin gel and intravenous administration of plain curcumin solution was studied by performing bio-distribution study in Swiss albino rats. Results: The results showed that all formulation variables i.e., the amount of capmul MCM (X1), Smix (accenon CC: transcutol P) (X2) and percentage of aqueous. Polycarbophil (X3) had a significant effect (p<0.05) on the responses. The developed MMEC was stable and non-ciliotoxic with 66.74 ± 3.46 nm and 98.58% ± 1.21 as average globule size and drug content, respectively. Polydispersibility index (0.133 ± 0.17) data and transmission electron microscopy study depicted the narrow size distribution of MMEC. Furthermore, following a comparative investigation of the brain uptake of curcumin among MMEC, plain drug gel and intravenous administration at 2.86 mg/kg, more brain uptake of curcumin was demonstrated for MMEC over intravenous application. Moreover, curcumin uptake in olfactory bulb after nasal administration of MMEC (31.11 ± 1.6) was than 9.44 times higher than intravenous injection of curcumin solution (3.25 ± 1.01). Area under curve represents the ratio of 2.86 mg/kg in brain tissue to plasma acquired afterward(s) the intranasal injection of MMEC (and it) was essentially greater than after the intravenous administration of curcumin solution. Conclusion: Findings of the investigation revealed that optimal MMEC and intranasal route may be considered to be promising and an alternative approach for brain targeting of curcumin.

7.
Mini Rev Med Chem ; 22(13): 1772-1788, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35049431

RESUMO

Bridged peptide macrobicycles (BPMs) from natural resources belong to types of compounds that are not investigated fully in terms of their formation, pharmacological potential, and stereo- chemical properties. This division of biologically active congeners with multiple circular rings has merits over other varieties of peptide molecules. BPMs form one of the most hopeful grounds for the establishment of drugs because of their close resemblance and biocompatibility with proteins, and these bio-actives are debated as feasible, realistic tools in diverse biomedical applications. Despite huge potential, poor metabolic stability and cell permeability limit the therapeutic success of macrocyclic peptides. In this review, we have comprehensively explored major bicyclic peptides sourced from plants and mushrooms, including ßs-leucyl-tryptophano-histidine bridged and tryptophanocysteine bridged peptide macrobicycles. The unique structural features, structure-activity relationship, synthetic routes, bioproperties, and therapeutic potential of the natural BPMs are also discussed.


Assuntos
Celosia , Amanita/metabolismo , Celosia/metabolismo , Peptídeos/química , Peptídeos Cíclicos/química
8.
Curr Org Synth ; 19(2): 267-278, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-34636301

RESUMO

AIMS: The present investigation is targeted towards the synthesis of a novel analogue of a natural peptide of marine origin. BACKGROUND: Marine sponges are enriched with bioactive secondary metabolites, especially circu-lar peptides. Heterocycles are established organic compounds with potential biological value. Tak-ing into consideration the bio-properties of heterocycles and marine sponge-derived natural pep-tides, an effort was made for the synthesis of a heterocyclic analogue of a natural cyclopeptide. OBJECTIVE: A heterocyclic analogue of a sponge-derived proline-containing cyclic peptide, rolloam-ide A, was synthesized by interaction of Boc-protected L-histidinyl-L-prolyl-L-valine and L-prolyl-L-leucyl-L-prolyl-L-isoleucine methyl ester and compared with synthetic rolloamide A with bioac-tivity against bacteria, fungi, and earthworms. METHODS: The synthesis of cycloheptapeptide was accomplished employing the liquid phase method. The larger peptide segment was prepared by interaction of Boc-protected L-prolyl-L-leu-cine with L-prolyl-L-isoleucine methyl ester. Similarly, the tripeptide unit was synthesized from Boc-protected L-histidinyl-L-proline with L-valine ester. The linear heptapeptide segment (7) was cyclized by utilizing pentafluorophenyl (pfp) ester, and the structure was elucidated by elemental and spectral (IR, 1H/13C NMR, MS) analysis. The peptide was also screened for diverse bioactivities such as antibacterial, antifungal, and potential against earthworms and cytotoxicity. RESULTS: The novel cyclooligopeptide was synthesized with 84% yield by making use of car-bodiimides. The synthesized cyclopeptide exhibited significant cytotoxicity against two cell lines. In addition, promising antifungal and antihelmintic properties were observed for newly synthesized heterocyclic peptide derivative (8) against dermatophytes and three earthworm species at 6 µg/mL and 2 mg/mL, respectively. CONCLUSION: Solution-phase technique employing carbodiimide chemistry was established to be promising for synthesizing the cycloheptapeptide derivative (8), and C5H5N was proved to be a better base for heptapeptide circling when compared to N-methylmorpholine and triethylamine.


Assuntos
Oligoquetos , Poríferos , Animais , Antifúngicos , Ésteres , Testes de Sensibilidade Microbiana , Peptídeos/farmacologia , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Poríferos/química , Prolina , Valina
9.
Arch Pharm (Weinheim) ; 354(8): e2100034, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33913195

RESUMO

Among peptide-based drugs, naturally occurring bicyclic compounds have been established as molecules with unique therapeutic potential. The diverse pharmacological activities associated with bicyclic peptides from marine tunicates, sponges, and bacteria render them suitable to be employed as effective surrogate between complex and small therapeutic moieties. Bicyclic peptides possess greater conformational rigidity and higher metabolic stability as compared with linear and monocyclic peptides. The antibody-like affinity and specificity of bicyclic peptides enable their binding to the challenging drug targets. Bridged macrobicyclic peptides from natural marine resources represent an underexplored class of molecules that provides promising platforms for drug development owing to their biocompatibility, similarity, and chemical diversity to proteins. The present review explores major marine-derived bicyclic peptides including disulfide-bridged, histidinotyrosine-bridged, or histidinoalanine-bridged macrobicyclic peptides along with their structural characteristics, synthesis, structure-activity relationship, and bioproperties.The comparison of these macrobicyclic congeners with linear/monocyclic peptides along with their therapeutic potential are also briefly discussed.


Assuntos
Organismos Aquáticos/metabolismo , Produtos Biológicos/farmacologia , Peptídeos Cíclicos/farmacologia , Animais , Produtos Biológicos/síntese química , Produtos Biológicos/química , Desenvolvimento de Medicamentos , Humanos , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/química , Relação Estrutura-Atividade
10.
Braz. J. Pharm. Sci. (Online) ; 53(2): e15223, 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-839489

RESUMO

ABSTRACT This study was to investigate the neuroprotective effect of curcumin against inflammation-mediated dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of Parkinson's disease (PD). Curcumin loaded sodium hyaluronate based mucoadhesive microemulsion (CMME) was developed by using Box Behnken design of Response surface method (RSM) and was characterized. Male C57BL/6 mice were first treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals followed CMME intranasal administration for 14 days at 2.86 mg of curcumin/kg of body weight per once a day. Optimal CMME containing 3% Capmul MCM as oil phase, 37 % of Accenon CC and Transcutol HP at 2.5:1 ratio and 0.5% sodium hyaluronate was stable, non-ciliotoxic with 57.66 nm±3.46 as average globule size. PdI value (0.190 ± 0.19) and TEM result depicted the narrow size distribution of CMME.All three independent variables had a significant effect (p<0.05) on the responses and the designed model was significant for all taken responses. In-vivo results revealed significant reduction of MPTP-mediated dopamine depletion after nasal administration of CMME. MPTP intoxication significantly decreased striatal DA content to 21.29 % which was then elevated to 55.37% after intranasal curcumin treatment. Significant improvement in motor performance as well as gross behavioural activity of mice was observed from rota-rod and open field test findings. Findings of the investigation revealed the symptomatic neuroprotection of curcumin against MPTP-induced neurodegradation in the striatum and hence could be considered as a promising approach to treat PD.


Assuntos
Animais , Masculino , Ratos , Doença de Parkinson/prevenção & controle , Curcumina/efeitos adversos , Administração Intranasal/estatística & dados numéricos , Metodologia como Assunto , Mucosa Nasal
11.
Saudi Pharm J ; 23(4): 352-65, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27134535

RESUMO

Poor solubility and bioavailability of an existing or newly synthesized drug always pose challenge in the development of efficient pharmaceutical formulation. Numerous technologies can be used to improve the solubility and among them amorphous solid dispersion based spray drying technology can be successfully useful for development of product from lab scale to commercial scale with a wide range of powder characteristics. Current review deals with the importance of spray drying technology in drug delivery, basically for solubility and bioavailability enhancement. Role of additives, selection of polymer, effect of process and formulation parameters, scale up optimization, and IVIVC have been covered to gain the interest of readers about the technology. Design of experiment (DoE) to optimize the spray drying process has been covered in the review. A lot more research work is required to evaluate spray drying as a technology for screening the right polymer for solid dispersion, especially to overcome the issue related to drug re-crystallization and to achieve a stable product both in vitro and in vivo. Based on the recent FDA recommendation, the need of the hour is also to adopt Quality by Design approach in the manufacturing process to carefully optimize the spray drying technology for its smooth transfer from lab scale to commercial scale.

12.
J Microencapsul ; 32(2): 193-200, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25535989

RESUMO

Micronisation of simvastatin dissolved in acetone, dimethyl sulfoxide and ethanol with supercritical carbon dioxide as antisolvent was successfully performed using a supercritical antisolvent technique. The effect of a few process parameters such as precipitation temperature, the pressure and solute concentration in the liquid solution has been studied to evaluate their influence on morphology and size of particles. The micronised simvastatin were evaluated for drug content, particle size analysis and in vitro dissolution profiles. Fourier transform infrared spectroscopy, differential scanning calorimetry and PXRD patterns was used to study the possible changes after micronisation of simvastatin. The dissolution rate was increased after micronised compared with pure simvastatin in distilled water, pH 1.2 buffer and pH 7.0 buffer. In vivo performance of the optimised formulation was evaluated in rats using pharmacodynamic marker parameters like serum total cholesterol (CH) and triglycerides (TG) for 21 days. Pharmacodynamic studies of micronised simvastatin revealed improved reduction in CH and TG values as compared with pure simvastatin indicating improved bioavailability. In vivo pharmacokinetics in rats showed an increase in bioavailability of micronised simvastatin (3.14 times) compared with plain simvastatin.


Assuntos
Acetona/química , Dióxido de Carbono/química , Dimetil Sulfóxido/química , Liberação Controlada de Fármacos , Etanol/química , Sinvastatina , Animais , Feminino , Masculino , Ratos , Ratos Wistar , Sinvastatina/química , Sinvastatina/farmacocinética , Sinvastatina/farmacologia
13.
Recent Pat Drug Deliv Formul ; 8(1): 63-78, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24720661

RESUMO

Spray drying has always remained an energetic field of innovation in pharmaceutical, food and flavor industry since last couple of decades. The current communication embodies an in-depth application of spray drying in pulmonary drug delivery for production of uniform and respirable size particles suitable for nebulizers, dry powder inhalers (DPI) and pressurized metered dose inhalers (pMDI). The review also highlights spray drying application in the manufacturing of mucoadhesive formulation suitable for nasal cavities to improve the drug absorption and bioavailability. Recent research works and patents filed by various researchers on spray drying technology for solubility enhancement have also been accentuated. Benefits of spray drying in production of dry flavorings to meet a product with maximum yield and least flavor loss are also discussed. The use of spray drying in production of various food products like milk or soymilk powder, tomato pulp, dry fruit juice etc, and in encapsulation of vegetable oil or fish oil and dry creamer has been discussed. Current review also highlights the application of spray drying in the biotechnology field like production of dry influenza or measles vaccine as well as application in ceramic industry. Spray drying based patents issued by the U.S. Patent and Trademark Office in the area of drug delivery have also been included in the current review to emphasize importance of spray drying in the recent research scenario.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Aromatizantes/administração & dosagem , Indústria Alimentícia/métodos , Inaladores Dosimetrados , Patentes como Assunto , Tecnologia Farmacêutica/métodos , Administração por Inalação , Administração Intranasal , Biotecnologia/métodos , Inaladores de Pó Seco , Humanos , Nebulizadores e Vaporizadores , Tamanho da Partícula , Solubilidade
14.
Sci Pharm ; 82(4): 749-63, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26279975

RESUMO

A simple, rapid, and highly selective RP-HPLC method was developed for the simultaneous determination of Ambrisentan (AMB) and Tadalafil (TADA) drug substances in the fixed dosage strength of 10 mg and 40 mg, respectively. Effective chromatographic separation was achieved using a Hypersil GOLD C18 column (150 mm × 4.6 mm internal diameter, 5 µm particle size) with a mobile phase composed of methanol, water, and acetonitrile in the ratio of 40:40:20 (by volume). The mobile phase was pumped using a gradient HPLC system at a flow rate of 0.5 mL/min, and quantification of the analytes was based on measuring their peak areas at 260 nm. The retention times for Ambrisentan and Tadalafil were about 2.80 and 7.10 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection, and quantification limits. Calibration curves were linear in the ranges of 1-20 µg/mL for Ambrisentan and 4-80 µg/mL for Tadalafil with correlation coefficients >0.990. The proposed method proved to be selective and stability-indicating by the resolution of the two analytes from the forced degradation (hydrolysis, oxidation, and photolysis) products. The validated HPLC method was successfully applied to the analysis of AMB and TADA in pharmaceutical dosage form.

15.
Sci Pharm ; 82(3): 541-54, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25853066

RESUMO

A simple, rapid, and highly selective RP-HPLC method was developed for the simultaneous determination of Azelnidipine (AZL) and Olmesartan (OLM) drug substances in the fixed dosage strength of 16 mg and 20 mg, respectively. Effective chromatographic separation was achieved using a Hypersil GOLD C18 column (150 mm × 4.6 mm internal diameter, 5 µm particle size) with a mobile phase composed of methanol, acetonitrile, and water in the ratio of 40:40:20 (by volume). The mobile phase was pumped using a gradient HPLC system at a flow rate of 0.5 mL/min, and quantification of the analytes was based on measuring their peak areas at 260 nm. The retention times for Azelnidipine and Olmesartan were about 8.56 and 3.04 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection, and quantification limits. Calibration curves were linear in the ranges of 2-48 µg/mL for Azelnidipine and 2.5-60 µg/mL for Olmesartan with correlation coefficients >0.990. The proposed method proved to be selective and stability-indicating by the resolution of the two analytes from the forced degradation (hydrolysis, oxidation, and photolysis) products. The validated HPLC method was successfully applied to the analysis of AZL and OLM in their combined dosage form.

16.
Curr Drug Deliv ; 10(4): 384-93, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23909665

RESUMO

Poor bioavailability and therapeutic response of conventional therapy due to many pre-corneal constraints necessitate the development of novel controlled and sustained ocular drug delivery to become a standard one in modern pharmaceutical era. This investigation aimed to study the drug release kinetics of betaxolol hydrochloride from a hydrophobic matrix system of PMMA cast with incorporating different proportions of polyethylene oxide (PEO) and evaluate its ability to improve ocular bioavailability and duration of action for the drug. Matrix type ocular inserts were prepared by the film casting technique and characterized in vitro by drug release studies using a flow through apparatus that simulated the eye conditions. All the formulations were subjected to physicochemical evaluation. Rabbit model with steroid induced glaucoma was used to establish in vivo efficacy of inserts. Polymer composition and concentration significantly affected the drug release based on change in diffusional path length and formation of gelaneous pores by polymer erosion. Formulations released the drug by non-fickian diffusion including anomalous transport (0.51). It was also observed that increasing the proportion of PEO in to PMMA does not affect the blend miscibility. IVIVC suggested no significant difference (P< 0.001) between in vitro and in vivo release of drug from inserts. In vivo IOP lowering activity was better for optimized insert F8 (for 24 h) as compared to eye drops (10 h). This ocular insert could be a promising once-a-day sustained release formulation for treating glaucoma.


Assuntos
Anti-Hipertensivos/administração & dosagem , Betaxolol/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Sistemas de Liberação de Medicamentos , Administração Oftálmica , Animais , Anti-Hipertensivos/química , Betaxolol/química , Preparações de Ação Retardada/química , Excipientes/química , Feminino , Interações Hidrofóbicas e Hidrofílicas , Masculino , Polietilenoglicóis/química , Polimetil Metacrilato/química , Coelhos , Resistência à Tração
17.
Braz. arch. biol. technol ; 56(2): 223-236, Mar.-Apr. 2013. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-675640

RESUMO

The present study was performed to design and evaluate the famotidine loaded mucoadhesive nanosuspension for aspirin induced ulcer. A 3-factor, 3-level Box-Behnken design was applied to study the effects of amount of the beads (X1), PVPK-30(X2) and Tween-80 (X3) on the particle size (Y1), and cumulative percentage drug released after 1h (Y2). The optimization was performed using the desirability function and contour plots. The scanning electron microscopy (SEM) showed the nanoparticles as spherical in shape. The differential scanning calorimetry (DSC) analysis indicated that there was substantial crystallinity change in the nanoparticle compared with the pure drug. Ex-vivo mucoadhesion study showed that famotidine mucoadhesive nanoparticles possessed higher mucoadhesion than the famotidine nanoparticles. The in vivo studies on aspirin-induced rats indicated the lowering in ulcer index for famotidine mucoadhesive nanoparticles was 0.46+0.011, which was significantly better than the effect of traditional famotidine suspension (0.66+0.035). Famotidine mucoadhesive nanosuspension could be prepared using the media milling technique and allowing significant reduction in ulcer index compared to famotidine suspension.

18.
Curr Drug Deliv ; 10(3): 317-25, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23286919

RESUMO

The mucoadhesive microparticles (CHCNZ) composed of chitosan (CH) and cinnarizine (CNZ) hydrochloride were successfully prepared, in a process of solution-enhanced dispersion, by supercritical CO2 (SEDS) technique. Scanning electron microscopy was used to reveal the morphological characteristics of mucoadhesive microparticles. The average particle size of microparticles was in the range from 1.9 to 12.8 µm. In vitro and in vivo mucoadhesive tests showed that CHCNZ mucoadhesive microparticles adhered more strongly to gastric mucous layer. Thereby retaining in gastrointestinal tract for an extended period of time and exhibiting good mucoadhesive properties. The X-ray powder diffractometry and differential scanning calorimetry analysis demonstrated that the SEDS process was an efficient physical coating process to produce CHCNZ composite microparticles. It also suggests that CNZ did not undergo chemical changes during the production of microparticles. The optimized batch exhibited a high drug entrapment efficiency of 67% with particle size of 3.9 µm. A sustained pattern of drug release was obtained for more than 20 h. In vivo studies were carried out by administering orally cinnarizine HCl (CNZ) suspension and mucoadhesive microparticles to rabbits under fasted (for 12 h) conditions. The results showed that CNZ mucoadhesive microparticles had a better bioavailability than CNZ suspension due to longer retention in the gastric environment of the test animals.


Assuntos
Cinarizina/química , Adesividade , Animais , Química Farmacêutica/métodos , Quitosana/química , Cromatografia com Fluido Supercrítico , Cinarizina/administração & dosagem , Cinarizina/farmacocinética , Feminino , Mucosa Gástrica/química , Técnicas In Vitro , Masculino , Coelhos , Ratos
19.
J Pharm Bioallied Sci ; 4(Suppl 1): S84-5, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23066219

RESUMO

THE PRESENT INVESTIGATION DESCRIBED THE INFLUENCE OF VISCOSITY AND DRUG: Polymer ratio on Hydrochlorothiazide release. Floating microspheres loaded with hydrochlorothiazide were prepared by Emulsion solvent evaporation method. The prepared microspheres were evaluated by micromeritics properties, in vitro drug release, floating ability and drug entrapment efficiency.

20.
J Pharm Bioallied Sci ; 4(Suppl 1): S86-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23066220

RESUMO

The objective of this work was to apply central composite experimental design to investigate main and interaction effect of formulation parameters in optimizing novel fast disintegration tablets formulation using pullulan as diluents. Face centered central composite experimental design was employed to optimize fast disintegration tablet formulation. The variables studied were concentration of diluents (pullulan, X(1)), superdisintigrant (sodium starch glycolate, X(2)), and direct compression aid (spray dried lactose, X(3)). Tablets were characterized for weight variation, thickness, disintegration time (Y(1)) and hardness (Y(2)). Good correlation between the predicted values and experimental data of the optimized formulation methodology in optimizing fast disintegrating tablets using pullulan as a diluent.

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