Biswanath Sa

Interpenetrating network hydrogel membranes of sodium alginate and poly(vinyl alcohol) for controlled release of prazosin hydrochloride through skin

Interpenetrating network (IPN) hydrogel membranes of sodium alginate (SA) and poly(vinyl alcohol) (PVA) were prepared by solvent casting method for transdermal delivery of an anti-hypertensive drug, prazosin hydrochloride. The prepared membranes were thin, flexible and smooth. The X-ray diffraction studies indicated the amorphous dispersion of drug in the membranes. Differential scanning calorimetric analysis confirmed the IPN formation and suggests that the membrane stiffness increases with increased concentration of glutaraldehyde (GA) in the membranes. All the membranes were permeable to water vapors depending upon the extent of cross-linking. The in vitro drug release study was performed through excised rat abdominal skin; drug release depends on the concentrations of GA in membranes. The IPN membranes extended drug release up to 24 h, while SA and PVA membranes discharged the drug quickly. The primary skin irritation and skin histopathology study indicated that the prepared IPN membranes were less irritant and safe for skin application.

Development of Fast Dispersible Aceclofenac Tablets: Effect of Functionality of Superdisintegrants

Aceclofenac, a non-steroidal antiinflammatory drug, is used for posttraumatic pain and rheumatoid arthritis. Aceclofenac fast-dispersible tablets have been prepared by direct compression method. Effect of superdisintegrants (such as, croscarmellose sodium, sodium starch glycolate and crospovidone) on wetting time, disintegration time, drug content, in vitro release and stability parameters has been studied. Disintegration time and dissolution parameters (t50% and t80%) decreased with increase in the level of croscarmellose sodium. Where as, disintegration time and dissolution parameters increased with increase in the level of sodium starch glycolate in tablets. However, the disintegration time values did not reflect in the dissolution parameter values of crospovidone tablets and release was dependent on the aggregate size in the dissolution medium. Stability studies indicated that tablets containing superdisintegrants were sensitive to high humidity conditions. It is concluded that fast-dispersible aceclofenac tablets could be prepared by direct compression using superdisintegrants.

Evaluation of pH-Sensitivity and Drug Release Characteristics of (Polyacrylamide-Grafted-Xanthan)–Carboxymethyl Cellulose-Based pH-Sensitive Interpenetrating Network Hydrogel Beads

Novel pH-sensitive interpenetrating network hydrogel beads of polyacrylamide-grafted-xanthan (PAAm-g-XG) and sodium carboxymethyl cellulose (NaCMC) loaded with ketoprofen were prepared and evaluated for pH sensitivity and drug release characteristics. The pH-sensitive PAAm-g-XG copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The grafting and alkaline hydrolysis reactions were confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and X-ray diffraction studies were carried out to know the crystalline nature of encapsulated drug. Scanning electron microscopic study revealed that the interpenetrating polymer network (IPN) beads possess porous matrix structure in alkaline pH whereas nonporous matrix structure was observed in acidic pH. The swelling of the beads and drug release was significantly increased when pH of the medium was changed from acidic to alkaline. The results of pulsatile swelling study indicated that the IPN beads changed their swelling behavior when pH of the external medium was altered. As pH of the medium was changed from 1.2 to 7.4, a considerable increase in swelling was observed for all the beads. However, swelling process was slower than the deswelling. At higher pH values, the carboxyl functional groups of hydrogels undergo ionization and the osmotic pressure inside the beads increases resulting in higher swelling. Drug release followed case II transport mechanism in acidic medium whereas anomalous/non-Fickian transport mechanism was observed in alkaline medium.

Novel pH-sensitive interpenetrating network hydrogel beads of carboxymethylcellulose-(polyacrylamide-grafted-alginate) for controlled release of ketoprofen: preparation and characterization.

Novel pH-sensitive carboxymethylcellulose-(polyacrylamide-grafted-sodium alginate) interpenetrating network (IPN) hydrogel beads loaded with ketoprofen were prepared using ionotropic gelation and covalent crosslinking method. Polyacrylamide-grafted-sodium alginate (PAAm-g-SA) copolymer was synthesized by free radical polymerization using ammonium persulfate (APS) as free radical initiator under the nitrogen atmosphere followed by hydrolysis using sodium hydroxide. The grafting, alkaline hydrolysis and crosslinking reactions were confirmed by Fourier transform infrared spectroscopy (FTIR). Beads were characterized by differential scanning calorimetric (DSC) analysis, thermogravimetric analysis (TGA), X-ray diffractometry (XRD) and scanning electron microscopy (SEM). The mechanical properties of the prepared IPNs were investigated. The erosion was observed with the beads containing only ionic crosslinks whereas it was negligible with the beads containing both ionic and covalent crosslinks. The swelling of the beads and drug release was significantly increased when pH of the medium was changed from acidic to alkaline (P<0.05). The swelling and release data were fitted to an empirical equation to determine the transport mechanism. Drug release followed case II transport mechanism in acidic medium whereas anomalous/non-Fickian transport mechanism was observed in alkaline medium.

Novel interpenetrating network microspheres of xanthan gum-poly(vinyl alcohol) for the delivery of diclofenac sodium to the intestine--in vitro and in vivo evaluation.

Xanthan gum (XG), a trisaccharide branched polymer and poly vinyl alcohol (PVA), was used to develop pH-sensitive interpenetrating network (IPN) microspheres by emulsion cross-linking method in the presence of glutaraldehyde as a cross-linker to deliver model anti-inflammatory drug, diclofenac sodium (DS) to the intestine. Various formulations were prepared by changing the ratio of XG:PVA, extent of cross-linking in order to optimize the formulation variables on drug encapsulation efficiency, and release rate. Formation of interpenetrating network and the chemical stability of DS after penetration of microspheres was confirmed by Fourier Transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis were done on the drug loaded microspheres which confirmed molecular dispersion of DS in the IPN. Microspheres formed were spherical with smooth surfaces, as evidenced by scanning electron microscopy (SEM), and mean particle size, as measured by laser light scattering technique ranged between 310.25–477.10 µm. Drug encapsulation of up to 82.94% was achieved as measured by UV method. Both equilibrium and dynamic swelling studies and in vitro release studies were performed in pH 1.2 and 6.8. Release data indicated a Fickian trend of drug release which depends on the extent of cross-linking and the ratio of XG:PVA present in the microsphere. When subjected to in vivo pharmacokinetic evaluation in rabbits, microparticles show slow and prolonged drug release when compared with DS solution. Based on the results of in vitro and in vivo studies it was concluded that these IPN microspheres provided oral controlled release of water-soluble DS.

Organic–Inorganic Composites for Bone Drug Delivery

This review paper attempts to provide an overview in the fabrication and application of organic–inorganic based composites in the field of local drug delivery for bone. The concept of local drug delivery exists for a few decades. However, local drug delivery in bone and specially application of composites for delivery of drugs to bone is an area for potential research interest in the recent time. The advantages attained by an organic–inorganic composite when compared to its individual components include their ability to release drug, adopting to the natural environment and supporting local area until complete bone regeneration, which make them carriers of interest for local drug delivery for bone.

Development and evaluation of polyethyleneimine-treated calcium alginate beads for sustained release of diltiazem

The objective of this investigation is to develop a multi-unit sustained release dosage form of a water soluble drug from a completely aqueous environment avoiding the use of any organic solvent. The drug was complexed with resin and calcium alginate or polyethyleneimine-treated calcium alginate beads loaded with the resinate were prepared by a ionic/polyelectrolyte complexation method. The effect of different formulation variables on the characteristics of the beads was investigated. Although the drug release from spherical and smooth-surfaced calcium alginate beads in both acidic and alkaline dissolution media were slower than those obtained from plain resinate, none of the variables were found to prolong the drug release considerably due to rapid swelling and disintegration of calcium alginate beads in alkaline medium. On the other hand, drug release from polyethyleneimine-treated calcium alginate beads in acidic medium did not increase appreciably following a burst release. However, in alkaline medium, the drug release was found to increase gradually and extend over a different period of time depending on the intensity of polyethyleneimine treatment. Scanning electron micrographs revealed the formation of a dense membrane around the resinate-loaded calcium alginate matrix. The membrane appeared to be responsible for reduced swelling and protracted disintegration of the beads resulting in slow release of the drug. The results indicate that sustained release of a water soluble drug from polyethyleneimine-treated calcium alginate beads could be achieved by adjusting the formulation variables.

Enteric delivery of ketoprofen through functionally modified poly(acrylamide-grafted-xanthan)-based pH-sensitive hydrogel beads: Preparation, in vitro and in vivo evaluation

Novel pH-sensitive hydrogel beads were prepared using a hydrolyzed poly(acrylamide-g-xanthan) (PAAm-g-XG) copolymer from a complete aqueous environment and evaluated for targeting ketoprofen to the intestine. The PAAm-g-XG copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The copolymer was characterized by FTIR spectroscopy, 1H NMR spectroscopy, elemental analysis and thermogravimetric analysis. Pulsatile swelling study indicated that the copolymer exhibits considerable pH-sensitive behavior unlike pristine xanthan gum. Ketoprofen-loaded pH-sensitive beads were prepared by ionotropic gelation with Al3 + ions. Release of drug from all the copolymeric beads was much lesser than that from pristine xanthan beads. Moreover, a maximum of 20% ketoprofen was released from the copolymeric beads in pH 1.2–5.5 during a period of 3 h, while a major portion of the drug was released in pH 6.8–7.4 gradually over a longer period. Pharmacodynamic activity and stomach histopathology of albino rats indicated that the beads were able to retard the drug release in stomach, and gastric side effects such as ulceration, hemorrhage and erosion of gastric mucosa were diminished when the drug was entrapped into PAAm-g-XG-based pH-sensitive beads.

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.

Tailoring of locust bean gum and development of hydrogel beads for controlled oral delivery of glipizide

In this study, carboxymethyl derivative of locust bean gum was prepared, characterized, and its gelling ability with different concentrations (1–5% w/v) of aluminum chloride (AlCl3) was utilized for the development of glipizide-loaded beads in a completely aqueous environment. The beads were spherical when observed under a scanning electron microscope. Increase in gelling ion concentration decreased the drug entrapment efficiency from 97.68% to 95.14%. The beads swelled more slowly in pH 1.2 KCl-HCl buffer and exhibited a slower drug release pattern than that observed in pH 7.4 phosphate buffer. Irrespective of the dissolution media, the drug release became slower at higher AlCl3 concentration. The drug release in alkaline medium was found to be controlled by a combination of diffusion as well as polymer relaxation phenomena. Comparing the release profiles, it was observed that the beads treated with 5% AlCl3 provided slower drug release up to 10 h in alkaline medium without any sign of disintegration and, thus, this formulation was selected for further studies. Fourier transform infrared (FTIR) spectroscopy indicated the stable nature of the drug in the beads. Differential scanning calorimetry and X-ray diffraction analysis showed that most of the drug remained in amorphous state in the beads. Stability study indicated no statistical significant difference in drug entrapment efficiency of the beads. In vivo activity of the beads was tested and a prolonged hypoglycemic effect was achieved. Hence, carboxymethyl locust bean beads could be a potential carrier for controlled oral delivery of glipizide.