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1.
Arch Pharm (Weinheim) ; 354(8): e2100034, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33913195

ABSTRACT

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.


Subject(s)
Aquatic Organisms/metabolism , Biological Products/pharmacology , Peptides, Cyclic/pharmacology , Animals , Biological Products/chemical synthesis , Biological Products/chemistry , Drug Development , Humans , Peptides, Cyclic/chemical synthesis , Peptides, Cyclic/chemistry , Structure-Activity Relationship
2.
J Microencapsul ; 32(2): 193-200, 2015.
Article in English | MEDLINE | ID: mdl-25535989

ABSTRACT

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.


Subject(s)
Acetone/chemistry , Carbon Dioxide/chemistry , Dimethyl Sulfoxide/chemistry , Drug Liberation , Ethanol/chemistry , Simvastatin , Animals , Female , Male , Rats , Rats, Wistar , Simvastatin/chemistry , Simvastatin/pharmacokinetics , Simvastatin/pharmacology
3.
Saudi Pharm J ; 23(4): 352-65, 2015 Sep.
Article in English | MEDLINE | ID: mdl-27134535

ABSTRACT

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.

4.
Int J Pharm Compd ; 27(1): 60-71, 2023.
Article in English | MEDLINE | ID: mdl-36720063

ABSTRACT

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.


Subject(s)
Ibuprofen , Nanoparticles , Ibuprofen/chemistry , Excipients/chemistry , Solvents , Water , Solubility , Nanoparticles/chemistry , Tablets/chemistry
5.
Int J Pharm Compd ; 27(1): 78-87, 2023.
Article in English | MEDLINE | ID: mdl-36720065

ABSTRACT

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.


Subject(s)
Disaccharides , Excipients , Powders , Disaccharides/chemistry , Excipients/chemistry , Sugar Alcohols/chemistry , Solubility
6.
Ren Fail ; 34(4): 521-32, 2012.
Article in English | MEDLINE | ID: mdl-22264075

ABSTRACT

Tissue hypoxia is a pathologic feature of many human diseases like cancer, myocardial infarction, stroke, and kidney disease. Convincing data from clinical studies in patients with chronic renal failure point to chronic hypoxia of kidneys as the end result of multiple processes and mechanisms. In acute as well as chronic diseases, tissue hypoxia not only implies a risk of energy deprivation but also induces regulatory mechanisms with profound influence on gene expression. Moreover, once established, accumulating evidence points to this chronic hypoxia as the central player along with final common pathway to end-stage renal disease (ESRD). An evolutionarily preserved oxygen-sensing mechanism enables cells to adapt and maintain homeostasis under hypoxic conditions by transcriptional activation of a host of genes mediating metabolic adaptation, angiogenesis, energy conservation, erythropoiesis, in addition to cell survival. The endogenous oxygen-sensing mechanism incorporates hypoxia-inducible factors (HIFs) that hub cellular response to hypoxia and comprises a family of oxygen-sensitive basic helix-loop-helix proteins that control the cellular transcriptional response to hypoxia. Hypoxia-inducible factor 1 (HIF-1) is thus a significant mediator of physiological responses to acute and chronic hypoxia. Since HIF is activated to suboptimal levels in pathogenic renal states, therapeutic activation holds a promising novel and effective approach to the treatment of ESRD. Current insights into the regulation of HIF may augment the understanding of the role of hypoxia in renal failure progression and may unbolt new options to improve hypoxia tolerance and induce nephroprotection.


Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis , Kidney Failure, Chronic/metabolism , Animals , Disease Progression , Gene Expression Regulation , Humans , Hypoxia/complications , Hypoxia/genetics , Hypoxia/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/therapy , Oxidative Stress
7.
Curr Org Synth ; 19(2): 267-278, 2022 03 03.
Article in English | MEDLINE | ID: mdl-34636301

ABSTRACT

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.


Subject(s)
Oligochaeta , Porifera , Animals , Antifungal Agents , Esters , Microbial Sensitivity Tests , Peptides/pharmacology , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Porifera/chemistry , Proline , Valine
8.
Mini Rev Med Chem ; 22(13): 1772-1788, 2022.
Article in English | MEDLINE | ID: mdl-35049431

ABSTRACT

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.


Subject(s)
Celosia , Amanita/metabolism , Celosia/metabolism , Peptides/chemistry , Peptides, Cyclic/chemistry
9.
Pharmazie ; 66(2): 124-9, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21434575

ABSTRACT

Budesonide is a potent glucocorticoid with high affinity for the glucocorticoid receptor, which is used for the treatment of inflammatory bowel diseases. Current oral formulations of budesonide present low efficacy against ulcerative colitis because of the premature drug release in the upper part of the gastrointestinal tract. The objective of this study was to develop a colon specific delivery system for budesonide to increase the efficacy in the treatment of ulcerative colitis using a statistical procedure. Pellets were prepared by powder layering of budesonide on nonpareils (0.5-0.6 mm) in a coating pan. Drug-layered pellets were coated with an inner layer of a combination of Eudragit RL PO and RS PO and an outer layer of Eudragit FS in a fluidized-bed apparatus. Central composite design was used to study the effect of three independent variables. The independent variables selected were amount of Eudragit FS outer coating (X1), proportion of Eudragit RL PO in the inner coating (X2), amount of Eudragit RL PO-RS PO inner coating (X3). Fifteen batches were prepared and evaluated for amount of drug released in 6 h (Y1), amount of drug released in 12h (Y2). The proportion of the more hydrophilic polymer Eudragit RL PO had the most significant effect on drug release - higher proportion gave faster release; the amount of inner and outer coat did not have a significant effect on the rate of drug release at either 6 or 12 h in the range studied. The computer optimization process and contour plots predicted the levels of independent variables X1, X2, and X3 (0.79, 0.69 and 0.35 respectively), for colon targeting.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Budesonide/administration & dosage , Colitis, Ischemic/drug therapy , Colon/metabolism , Algorithms , Anti-Inflammatory Agents/pharmacokinetics , Budesonide/pharmacokinetics , Chemistry, Pharmaceutical , Drug Delivery Systems , Drug Design , Humans , Microscopy, Electron, Scanning , Models, Theoretical , Polymethacrylic Acids , Software , Solubility , Surface Properties
10.
J Pharm Pharm Sci ; 13(4): 536-57, 2010.
Article in English | MEDLINE | ID: mdl-21486530

ABSTRACT

Chitosan has prompted the continuous movement for the development of safe and effective drug delivery systems because of its unique physicochemical and biological characteristics. The primary hydroxyl and amine groups located on the backbone of chitosan allow for chemical modification to control its physical properties. When the hydrophobic moiety is conjugated to a chitosan molecule, the resulting amphiphile may form self-assembled nanoparticles that can encapsulate a quantity of drugs and deliver them to a specific site of action. Chemical attachment of the drug to the chitosan throughout the functional linker may produce useful prodrugs, exhibiting the appropriate biological activity at the target site. Mucoadhesive and absorption enhancement properties of chitosan increase the in vivo residence time of the dosage form in the gastrointestinal tract and improve the bioavailability of various drugs. The main objective of this review is to provide an insight into various target-specific carriers, based on chitosan and its derivatives. The first part of the review is concerned with the organ-specific delivery system using chitosan and its derivatives. The subsequent section considers the recent developments of drug delivery carriers for cancer therapy with special focus on various targeting strategies.


Subject(s)
Chitosan/chemistry , Drug Carriers/chemistry , Drug Delivery Systems , Adhesiveness , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Biological Availability , Humans , Neoplasms/drug therapy , Neoplasms/pathology , Pharmaceutical Preparations/administration & dosage
11.
J Microencapsul ; 26(4): 365-76, 2009 Jun.
Article in English | MEDLINE | ID: mdl-18720199

ABSTRACT

The purpose of this research was to formulate and systemically evaluate in vitro and in vivo performances of mucoadhesive amoxicillin microspheres for the potential use in the treatment of gastric and duodenal ulcers, which were associated with Helicobacter pylori. Amoxicillin mucoadhesive microspheres containing carbopol-934P as mucoadhesive polymer and ethyl cellulose as carrier polymer were prepared by an emulsion-solvent evaporation technique. Results of preliminary trials indicate that quantity of emulsifying agent, time for stirring, drug-to-polymers ratio and speed of rotation affected the characteristics of microspheres. Microspheres were discrete, spherical, free flowing and showed a good percentage of drug entrapment efficiency. An in vitro mucoadhesive test showed that amoxicillin mucoadhesive microspheres adhered more strongly to the gastric mucous layer and could retain in the gastrointestinal tract for an extended period of time. A 3(2) full factorial design was employed to study the effect of independent variables, drug-to-polymer-to-polymer ratio (amoxicillin-ethyl cellulose-carbopol-934P) (X(1)) and stirring speed (X(2)) on dependent variables, i.e. percentage mucoadhesion, drug entrapment efficiency, particle size and t(80). The best batch exhibited a high drug entrapment efficiency of 56%; mucoadhesion percentage after 1 h was 80% and the particle size was 109 µm. A sustained drug release was obtained for more than 12 h. The drug-to-polymer-to-polymer ratio had a more significant effect on the dependent variables. The morphological characteristics of the mucoadhesive microspheres were studied under a scanning electron microscope. In vitro release test showed that amoxicillin released slightly faster in pH 1.2 hydrochloric acid than in pH 7.8 phosphate buffer. In vivo H. pylori clearance tests were also carried out by administering amoxicillin powder and mucoadhesive microspheres to H. pylori infectious Wistar rats under fed conditions at single dose or multiple dose(s) in oral administration. The results showed that amoxicillin mucoadhesive microspheres had a better clearance effect than amoxicillin powder. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin might make a contribution to H. pylori complete eradication.


Subject(s)
Acrylates/chemistry , Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Helicobacter Infections/drug therapy , Microspheres , Stomach Ulcer/drug therapy , Amoxicillin/therapeutic use , Animals , Anti-Bacterial Agents/therapeutic use , Duodenal Ulcer/complications , Duodenal Ulcer/drug therapy , Helicobacter Infections/complications , Helicobacter pylori/drug effects , Humans , Male , Particle Size , Rats , Rats, Wistar , Stomach/microbiology , Stomach/pathology , Stomach Ulcer/complications
12.
Curr Drug Deliv ; 4(1): 41-50, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17269916

ABSTRACT

The purpose of this research was to formulate and systematically evaluate in vitro and in vivo performances of mucoadhesive amoxicillin microspheres for the potential use of treating gastric and duodenal ulcers, which were associated with Helicobacter pylori. Amoxicillin mucoadhesive microspheres containing chitosan as mucoadhesive polymer were prepared by simple emulsification phase separation technique using glutaraldehyde as a cross-linking agent. Results of preliminary trials indicate that volume of cross-linking agent, time for cross-linking, polymer-to-drug ratio, and speed of rotation affected characteristics of microspheres. Microspheres were discrete, spherical, free flowing and also showed high percentage drug entrapment efficiency. In vitro mucoadhesive test showed that amoxicillin mucoadhesive microspheres adhered more strongly to gastric mucous layer and could retain in gastrointestinal tract for an extended period of time. A 3(2) full factorial design was employed to study the effect of independent variables, polymer-to-drug ratio (X(1)), and stirring speed (X(2)) on dependent variables i.e. percentage mucoadhesion, t(80), drug entrapment efficiency, particle size and swelling index. The best batch exhibited a high drug entrapment efficiency of 70 % and a swelling index of 1.39; percentage mucoadhesion after 1 h was 79 %. The drug release was also sustained for more than 12 h. The polymer-to-drug ratio had a more significant effect on the dependent variables. The morphological characteristics of the mucoadhesive microspheres were studied using scanning electron microscopy. In vitro release test showed that amoxicillin released slightly faster in pH 1.0 hydrochloric acid than in pH 7.8 phosphate buffer. In vivo H. pylori clearance tests were also carried out by administering amoxicillin mucoadhesive microspheres and powder, to H. pylori infectious Wistar rats under fed conditions at single dose or multiple dose(s) in oral administration. The results showed that amoxicillin mucoadhesive microspheres had a better clearance effect than amoxicillin powder. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin might make contribution complete eradication of H. pylori.


Subject(s)
Amoxicillin/therapeutic use , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Microspheres , Stomach/drug effects , Acetic Acid/chemistry , Adhesiveness , Amoxicillin/chemistry , Amoxicillin/pharmacokinetics , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/therapeutic use , Biological Availability , Chitosan/chemistry , Dioctyl Sulfosuccinic Acid/chemistry , Drug Delivery Systems/methods , Drug Delivery Systems/standards , Glutaral/chemistry , Helicobacter Infections/microbiology , Helicobacter pylori/growth & development , Microscopy, Electron, Scanning , Mineral Oil/chemistry , Particle Size , Powders , Rats , Reproducibility of Results , Stomach/microbiology
13.
J Drug Target ; 14(2): 63-7, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16608733

ABSTRACT

Miniaturizing in chip technology, optics, micro mechanics, medicine, gene and biotechnology requires highly precise positioning techniques. The motivation for the new manipulation technology is the desire to enter the micro- and nanoworld not only by viewing but also acting, altering micro- and nanosized objects. A new era on medicine are expected to happen in the coming years. Due to the advances in the field of nanotechnology, nanodevice manufacturing has been growing gradually. From such achievements in nanotechnology and recent results in biotechnology and genetics, the first operating biological nanorobots are expected to appear in the coming 5 years and more complex diamondoid based nanorobots will become available in about 10 years. In terms of time, it means a very near better future with significant improvements in medicine.


Subject(s)
Nanotechnology/instrumentation , Robotics/instrumentation , Biocompatible Materials , Communication , Humans , Immune System , Nanostructures/adverse effects
14.
AAPS PharmSciTech ; 6(1): E49-55, 2005 Sep 20.
Article in English | MEDLINE | ID: mdl-16353963

ABSTRACT

The purpose of this research was to formulate and systematically evaluate in vitro and in vivo performances of mucoadhesive microspheres of glipizide. Glipizide microspheres containing chitosan were prepared by simple emulsification phase separation technique using glutaraldehyde as a cross-linking agent. Results of preliminary trials indicate that volume of cross-linking agent, time for cross-linking, polymer-to-drug ratio, and speed of rotation affected characteristics of microspheres. Microspheres were discrete, spherical, and free flowing. The microspheres exhibited good mucoadhesive property in the in vitro wash-off test and also showed a high percentage drug entrapment efficiency. A 3(2) full factorial design was employed to study the effect of independent variables, polymer-to-drug ratio (X(1) ), and stirring speed (X(2) ) on dependent variables percentage mucoadhesion, t(80), drug entrapment efficiency, and swelling index. The best batch exhibited a high drug entrapment efficiency of 75% and a swelling index of 1.42; percentage mucoadhesion after 1 hour was 78%. The drug release was also sustained for more than 12 hours. The polymer-to-drug ratio had a more significant effect on the dependent variables. In vivo testing of the mucoadhesive microspheres to albino Wistar rats demonstrated significant hypoglycemic effect of glipizide.


Subject(s)
Glipizide/chemistry , Glipizide/pharmacology , Microspheres , Tissue Adhesives/chemistry , Tissue Adhesives/pharmacology , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , Chemistry, Pharmaceutical , Drug Evaluation, Preclinical/methods , Rats , Rats, Wistar
16.
Sci Pharm ; 82(4): 749-63, 2014.
Article in English | MEDLINE | ID: mdl-26279975

ABSTRACT

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.

17.
Sci Pharm ; 82(3): 541-54, 2014.
Article in English | MEDLINE | ID: mdl-25853066

ABSTRACT

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.

18.
Recent Pat Drug Deliv Formul ; 8(1): 63-78, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24720661

ABSTRACT

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.


Subject(s)
Drug Delivery Systems/methods , Flavoring Agents/administration & dosage , Food Industry/methods , Metered Dose Inhalers , Patents as Topic , Technology, Pharmaceutical/methods , Administration, Inhalation , Administration, Intranasal , Biotechnology/methods , Dry Powder Inhalers , Humans , Nebulizers and Vaporizers , Particle Size , Solubility
19.
Curr Drug Deliv ; 10(4): 384-93, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23909665

ABSTRACT

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.


Subject(s)
Antihypertensive Agents/administration & dosage , Betaxolol/administration & dosage , Delayed-Action Preparations/administration & dosage , Drug Delivery Systems , Administration, Ophthalmic , Animals , Antihypertensive Agents/chemistry , Betaxolol/chemistry , Delayed-Action Preparations/chemistry , Excipients/chemistry , Female , Hydrophobic and Hydrophilic Interactions , Male , Polyethylene Glycols/chemistry , Polymethyl Methacrylate/chemistry , Rabbits , Tensile Strength
20.
Curr Drug Deliv ; 10(3): 317-25, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23286919

ABSTRACT

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.


Subject(s)
Cinnarizine/chemistry , Adhesiveness , Animals , Chemistry, Pharmaceutical/methods , Chitosan/chemistry , Chromatography, Supercritical Fluid , Cinnarizine/administration & dosage , Cinnarizine/pharmacokinetics , Female , Gastric Mucosa/chemistry , In Vitro Techniques , Male , Rabbits , Rats
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