Sanat Kumar Basu

Carbopol gel containing chitosan-egg albumin nanoparticles for transdermal aceclofenac delivery.

In the present work, various aceclofenac-loaded chitosan-egg albumin nanoparticles were prepared through heat coagulation method. These aceclofenac-loaded nanoparticles were characterized by FE-SEM, FTIR, DSC and P-XRD analyses. The in vitro drug release from nanoparticles showed sustained drug release over 8h. Aceclofenac-loaded nanoparticles (prepared using 200mg chitosan, 500 mg egg albumin and 2% (w/v) NaTPP) showed highest drug entrapment (96.32±1.52%), 352.90 nm average particle diameter and -22.10 mV zeta potential, which was used for further preparation of Carbopol 940 gel for transdermal application. The prepared gel exhibited sustained ex vivo permeation of aceclofenac over 8h through excised mouse skin. The in vivo anti-inflammatory activity in carrageenean-induced rats demonstrated comparative higher inhibition of swelling of rat paw edema by the prepared gel compared with that of the marketed aceclofenac gel over 4 h.

Aceclofenac-loaded chitosan-tamarind seed polysaccharide interpenetrating polymeric network microparticles.

The present work deals with the preparation, characterization and evaluation of glutaraldehyde cross-linked chitosan-tamarind seed polysaccharide (TSP) interpenetrating polymeric network (IPN) microparticles for prolonged aceclofenac release. The drug entrapment efficiency of these microparticles was found 85.84±1.75 to 91.97±1.30% and their average particle sizes were ranged from 490.55±23.24 to 621.60±53.57 μm. These chitosan-TSP IPN microparticles were characterized by FTIR, DSC, and SEM analyses. The in vitro drug release from these aceclofenac-loaded chitosan-TSP IPN microparticles showed sustained release of aceclofenac over 8h and followed the Korsmeyer-Peppas model (R(2)=0.9809-0.9828) with anomalous (non-Fickian) diffusion drug release mechanism. The in vivo studies exhibited sustained anti-inflammatory activity in carrageenan-induced rats over prolonged period after oral administration of these newly developed aceclofenac-loaded IPN microparticles.

Development of chitosan-based nanoparticles through inter-polymeric complexation for oral drug delivery

The possibility of inter-polymeric complexation of cationic chitosan and anionic egg albumin stabilized with PEG 400 to develop novel nanoparticles for oral delivery of alprazolam by heat coagulation method at pH 5.4 and 80 °C. Nine formulations were prepared by changing the concentration of chitosan, PEG 400 and heating time. The alprazolam entrapment efficiency of these nanoparticles was in the range of 68.12±1.27 to 99.37±4.86%. These nanoparticles were characterized by FTIR, DSC, P-XRD and FE-SEM analysis. Average particle diameter, poly-dispersity index and zeta potential of these nanoparticles were found 259.60 nm, 0.501, and -9.00 mV, respectively. The in vitro drug release from these alprazolam-loaded nanoparticles showed sustained drug release over a period of 24h. In conclusion, these newly developed chitosan-egg albumin-PEG nanoparticles were found to be a promising vehicle for sustained release delivery of lipophilic drugs.

Clinical concerns of immunogenicity produced at cellular levels by biopharmaceuticals following their parenteral administration into human body

Similar to the low molecular weight traditional drugs, biopharmaceuticals are capable of producing not only therapeutic effects but also side effects provided if the dose of these compounds exceeds certain concentration and/or if the exposure duration of these compounds at subtoxic doses is being lengthened. In addition, a major drawback of biopharmaceuticals is the risk of antibody formation. Following the administration of biopharmaceuticals into human body, the formation of antidrug–antibody (ADA) or neutralizing antibody and other general immune system effects (including allergy, anaphylaxis, or serum sickness) are of clinical concern regarding therapeutic efficacy and patient safety. For example, drug-induced neutralizing antibodies to erythropoietin (EPO) result in pure red cell aplasia, whereas drug-induced acquired anti-factor VIII antibodies worsen the pathology associated with hemophilia. Since most of the already developed or under development biopharmaceuticals are to some extent immunogenic, the regulatory agencies insist to conduct potential ADA formation during the drug development process itself. This review encompasses a short overview on the clinical concerns of immunogenicity produced at cellular levels by growth hormone, interferon-α, EPO, factor VIII, and factor IX following their parenteral administration into human body. Clinical concerns related to immunogenicity produced by the biosimilar versions of these drugs are also presented wherever possible.

Aceclofenac-loaded unsaturated esterified alginate/gellan gum microspheres: In vitro and in vivo assessment

Aceclofenac-loaded alginate/gellan gum microspheres for prolonged aceclofenac release were prepared through maleic anhydride-induced unsaturated esterification. The drug entrapment efficiency of these microspheres was found 39.30 ± 1.28% to 98.46 ± 0.40% and their average particle sizes were 270-490 μm. These microspheres were characterized by FTIR, DSC, P-XRD and SEM analysis. The in vitro dissolution indicated prolonged sustained release of aceclofenac over 6h, which also followed the Korsmeyer-Peppas model (R(2)=0.9571-0.9952). The microspheres prepared through 3% (w/v) maleic anhydride-induced esterification exhibited comparatively slower drug-release. Most of the microspheres were followed Fickian diffusion mechanism except the microspheres containing higher gellan gum content, which followed anomalous (non-Fickian) diffusion. The in vivo results showed sustained systemic absorption of aceclofenac in rabbits and excellent anti-inflammatory activity in carrageenan-induced rats after oral administration over prolonged period.

Development and evaluation of calcium alginate beads prepared by sequential and simultaneous methods

The objective of this study was to develop a sustained release dosage form of Trimetazidine dihydrochloride (TMZ) using a natural polymeric carrier prepared in a completely aqueous environment. TMZ was entrapped in calcium alginate beads prepared with sodium alginate by the ionotropic gelation method using calcium chloride as a crosslinking agent. The drug was incorporated either into preformed calcium alginate gel beads (sequential method) or incorporated simultaneously during the gelation stage (simultaneous method). The beads were evaluated for particle size and surface morphology using optical microscopy and SEM, respectively. Beads produced by the sequential method had higher drug entrapment. Drug entrapment in the sequential method was higher with increased CaCl2 and polymer concentration but lower with increased drug concentration. In the simultaneous method, drug entrapment was higher when polymer and drug concentration were increased and also rose to a certain extent with increase in CaCl2 concentration, where further increase resulted in lower drug loading. FTIR studies revealed that there is no interaction between drug and CaCl2. XRD studies showed that the crystalline drug changed to an amorphous state after formulation. Release characteristics of the TMZ loaded calcium alginate beads were studied in enzyme-free simulated gastric and intestinal fluid.

Evaluation of Ketorolac Tromethamine Microspheres by Chitosan/Gelatin B Complex Coacervation

Microspheres (MS) of Ketorolac Tromethamine (KT) for oral delivery were prepared by complex coacervation (method-1) and simple coacervation (method-2) methods without the use of chemical cross–linking agent (glutaraldehyde) to avoid the toxic reactions and other undesirable effects of the chemical cross-linking agents. Alternatively, ionotropic gelation was employed by using sodium-tripolyphosphate (Na-TPP) as cross linking agent. Chitosan and gelatin B were used as polymer and copolymer respectively. All the prepared microspheres were subjected to various physico-chemical studies, such as drug-polymer compatibility by Thin Layer Chromatography (TLC) and Fourier Transform Infra Red Spectroscopy (FTIR), surface morphology by Scanning Electron Microscopy (SEM), frequency distribution, encapsulation efficiency, in-vitro drug release characteristics and release kinetics. The physical state of drug in the microspheres was determined by Differential Scanning Calorimetry (DSC) and X-ray powder Diffractometry (XRD). TLC and FTIR studies indicated no drug-polymer incompatibility. All the MS showed release of drug by a fickian diffusion mechanism. DSC and XRD analysis indicated that the KT trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. It is possible to design a controlled drug delivery system for the prolonged release of KT, improving therapy by possible reduction of time intervals between administrations.

Evaluation of Ionotropic Cross-Linked Chitosan/Gelatin B Microspheres of Tramadol Hydrochloride

Microspheres of tramadol hydrochloride (TM) for oral delivery were prepared by complex coacervation method without the use of chemical cross-linking agents such as glutaraldehyde to avoid the toxic reactions and other undesirable effects of the chemical cross-linking agents. Alternatively, ionotropic gelation was employed by using sodium-tripolyphosphate as cross-linking agent. Chitosan and gelatin B were used as polymer and copolymer, respectively. All the prepared microspheres were subjected to various physicochemical studies, such as drug–polymer compatibility by thin layer chromatography (TLC) and Fourier transform infrared (FTIR) spectroscopy, surface morphology by scanning electron microscopy, frequency distribution, drug entrapment efficiency, in vitro drug release characteristics and release kinetics. The physical state of drug in the microspheres was determined by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). TLC and FTIR studies indicated no drug–polymer incompatibility. All the microspheres showed initial burst release followed by a fickian diffusion mechanism. DSC and XRD analysis indicated that the TM trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. From the preliminary trials, it was observed that it may be possible to formulate TM microspheres by using biodegradable natural polymers such as chitosan and gelatin B to overcome the drawbacks of TM and to increase the patient compliance.

In vitro aceclofenac release from IPN matrix tablets composed of chitosan-tamarind seed polysaccharide

This communication describes the formulation and in vitro evaluation of IPN matrix tablets of aceclofenac. IPN microparticles using chitosan and tamarind seed polysaccharide blend was prepared using glutaraldehyde as cross-linker. The drug entrapment efficiency and average particle size of these microparticles was found to be 91.97±1.30% and 498.12±38.67 μm, respectively. These IPN microparticles were characterized by scanning electron microscopy (SEM) and powder X-ray diffraction (P-XRD) study. These microparticles were compressed with tablet excipients through direct compression technique. These matrix tablets showed sustained aceclofenac release over 8 h. These matrix tablets might be helpful to minimize dosing frequency and reduction of various side effects during prolong period of treatment.

Evaluation of a glass ceramic coating for machine-tool slides

With a view to protect steel against mechanical wear and tear under dry sliding conditions, a glass-ceramic coating of composition RO-R′2O-Al2O3-SiO2 (R = Ca, Mg; R′ = Na, K, Li), with TiO2 and P2O5 as nucleation agents, has been applied on steel samples and their performances studied. The method of application of the glass-ceramic coating on steel is also discussed. Wear data have been fed for analysis of variance at 1% and 5% levels of significance and a normal factorial regression has been carried out to obtain a wear equation. The wear and coefficient of friction behaviour for both glass-ceramic-coated and uncoated steel, sliding against cast iron, has been plotted against time to obtain a quantitative measure of the improvement in wear resistance. The studies show that this new class of coating material can be highly useful for specialized engineering and industrial applications, particularly for increasing the life of sliding parts. Although various work has been done to prevent wear and tear of machine tool slides and guides through the use of suitable coatings, most of these technologies available are very costly, bringing down the economic viability of applying such coatings on machine tool slides. Here, a comparatively cheaper coating technology of glass-ceramic on steel has been evaluated statistically for solid-to-solid sliding operation. A wear equation derived from factorial regression for this coating, sliding against cast iron, as well as direct plotting of wear and friction values show an appreciable improvement in wear life for the coated samples.