Preparation of smart PVP/HPMC based IPN hydrogel, its characterization and toxicity evaluation.

In this study, the interpenetrating polymeric network (IPN) were fabricated via free radical polymerization using polymers hydroxypropyl methylcellulose (HPMC), Polyvinylpyrrolidone (PVP) and monomer Methacrylic acid (MAA) and also investigated their influence by changing their concentrations. The developed polymeric network is crosslinked via N' N' -methylene bis-acrylamide (MBA). Different characterizations have been performed to analyze fabricated interpenetrating polymeric network structure i.e., Scanning Electron Microscopy (SEM), X-ray Powder Diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FT-IR), Thermo-gravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). Letrozole (LTZ) was loaded as a model drug in the developed system. Swelling dynamics as well as drug release behavior were thoroughly examined. FTIR studies corroborated the formation of interpenetrating polymeric network. SEM uncovered porous structure while TGA depicted enhanced thermal stability of polymeric network. PXRD depicted amorphous dispersion of LTZ. Swelling dynamics as well as LTZ release behavior from developed interpenetrating polymeric network hydrogels were dependent upon pH of the medium and concentration of pure reactants employed. Higuchi model was best fit to regression coefficient which indicated diffusion controlled mechanism of drug release. Acute oral toxicity study depicted no mortality or any signs relating to acute toxicity throughout the whole observed period. Hence, the designed interpenetrating polymeric network might turn out to be a safe and a potential carrier system for the delivery of LTZ in the treatment of breast cancer (BC).

Antibacterial and clusteroluminogenic hypromellose-graft-chitosan-based polyelectrolyte complex films with high functional flexibility for food packaging.

Food packaging can extend the shelf life of food products and enhance the safety and quality of the food. This study reports food-grade polyelectrolyte complex films generated via electrostatic interactions between two cellulose-based agents [viz., hypromellose-graft-chitosan, and carmellose sodium]. At optimal conditions, our films show good barrier properties, high transparency, and high efficiency in post-production agent loading. They also demonstrate intrinsic antibacterial effects against both Gram-negative and Gram-positive bacteria. By using frozen chicken breasts as a model, the films enable real-time monitoring of the status of the frozen food due to the property of clusterisation-triggered emission. Along with their negligible toxicity, our films warrant further development as multi-functional films for effective and self-indicating food packaging.

Development of Sustained Release Oseltamivir Phosphate Dry Powder Inhaler: In-Vitro Characterization and In-Vivo Toxicological Studies.

BACKGROUND: Oseltamivir Phosphate (OP) is an ethyl ester prodrug prescribed for the treatment of influenza virus infection. Current marketed formulations of OP have been observed to be supplemented with an adverse effect during post-marketing surveillance. These prerequisites are sufficed by developing a sustained release Dry Powder for Inhalation (DPI). OBJECTIVE: The objective of the present study was to develop OP-DPI by an innovative formulation approach comprising of Immediate (IR) and Sustained (SR) Release portions. METHODS: DPI formulation comprising IR and SR portions were prepared by spray drying technique using Hydroxy Propyl Methyl Cellulose (HPMC) as the rate-controlling polymer for SR portion. The spray-dried product was further characterized for various pharmaco-technical, in-vitro and in-vivo parameters. RESULTS: OP-DPI showed a burst release of 49% within 15 min further sustaining the drug release up to 9 hrs. The in-vitro aerodynamic performance of OP-DPI showed maximum deposition at stage 3 and Fine Particle Dose (FPD) of 1.08 mg indicating deposition in the upper respiratory tract. Solid-state characterization by DSC and XRD indicated the partial amorphization of OP due to spray drying. In-vivo toxicological examination revealed no sign of inflammation, indicating the safety of the developed formulation. Accelerated stability study as per ICH guidelines displayed no significant change in the solid-state characterization and drug-related performance of OP-DPI. CONCLUSION: Prepared novel and scalable OP-DPI may have the potential to overcome the problems associated with existing marketed dosage forms of OP. Further, localized drug delivery of the antiviral drug through the pulmonary route might be clinically beneficial in controlling the viral proliferation.

Exploring the potential of tianeptine matrix tablets: Synthesis, physico-chemical characterization and acute toxicity studies.

The main objective of the present study was to explore the potential of matrix tablets as extended release dosage form of tianeptine, using HMPC K100 as a polymer. HPMC K100 extended the release of the drug from formulation due to the gel-like structure. Direct compression method was adopted to compress the tablets using different concentrations of polymer. Tablets were evaluated for pre-compression and post-compression parameters. Drug release study showed that tablet extends the release of drug with the increasing concentration of polymer. Drug, polymers and tablets were analyzed and/or characterized for compatibility, degradation, thermal stability, amorphous or crystalline nature via FTIR, DSC, TGA, XRD studies. SEM study predicted that tablets had a uniform structure. HPMC K100 based tablets were similar to that of the reference product. Acute toxicity study conducted on Swiss albino mice showed that matrix tablets were safe and non-toxic, as no changes in physical activity and functions of organs were observed. Biochemical and histopathological study revealed lack of any kind of abnormality in liver and renal function. Moreover, necrotic changes were absent at organ level.

Self-assembled micelles prepared from bio-based hydroxypropyl methyl cellulose and polylactide amphiphilic block copolymers for anti-tumor drug release.

Fully bio-based amphiphilic diblock copolymers were synthesized from hydroxypropyl methyl cellulose (HPMC) and amino-terminated poly(l-lactide) (PLLA) or poly(l-lactide-co-dl-lactide) (PLA) by reductive amination. The resulting HPMC-PLLA and HPMC-PLA copolymers with various hydrophobic block lengths were characterized by NMR, DOSY-NMR and FT-IR. Micelles were obtained by self-assembly of copolymers in aqueous medium. The micelles are spherical in shape, and the micelle size ranges from 150 to 180 nm with narrow distribution. The critical micelle concentration decreases with increasing PLA block length. Paclitaxel was loaded in micelles. Enhanced drug loading is obtained with increase of PLA block length. A biphasic release profile is observed with a burst of 40% followed by slower release up to 80%. MTT assay indicates the good cytocompatibility of HPMC-PLA micelles. SRB assay shows a significant cytotoxicity of paclitaxel-loaded micelles against SK-BR-3cells. It is thus concluded that bio-based HPMC-PLA block copolymers could be promising nano-carrier of anti-tumor drugs.

Formulation design and in vitro ex vivo evaluation of transdermal patches of Cinnarizine.

The aim of this study was to develop a Transdermal patch containing Cinnarizine using different ratios of hydrophilic and hydrophobic polymeric systems by solvent evaporation technique employing Polyethylene glycol (PEG 400) as plasticizer. The physicochemical compatibility of the drug and the polymers were studied by performing FT-IR spectroscopic analysis. Formulated patches were evaluated for physicochemical properties, skin irritation, in vitro drug release, ex-vivo permeation studies across rat abdominal skin and stability studies. The results of FT-IR studies revealed that there were no interactions between drug and polymers used. All the formulations exhibited uniformity in physicochemical properties. In vitro permeation studies of the formulations were performed by using Franz diffusion cells. Formulation F3 showed better permeation through rat skin (i.e., 8527.5±1.25µ/cm2 /hr) compared to rest of formulations and followed Fick's diffusion mechanism. On the basis of in-vitro drug release and ex-vivo skin permeation performance, Formulation F3 containing the polymeric blend 19:1 Hydroxypropylmethyl Cellulose (HPMC E 50cps: Eudragit RL 100) has shown optimum release in comparison to other formulations and indicated good physical stability. So it has been demonstrated that Cinnarizine can be designed as matrix type transdermal drug delivery system (TDDS) and further in-vivo evaluations were required.

Nanoemulsion-based electrolyte triggered in situ gel for ocular delivery of acetazolamide.

In the present work the antiglaucoma drug, acetazolamide, was formulated as an ion induced nanoemulsion-based in situ gel for ocular delivery aiming a sustained drug release and an improved therapeutic efficacy. Different acetazolamide loaded nanoemulsion formulations were prepared using peanut oil, tween 80 and/or cremophor EL as surfactant in addition to transcutol P or propylene glycol as cosurfactant. Based on physicochemical characterization, the nanoemulsion formulation containing mixed surfactants and transcutol P was selected to be incorporated into ion induced in situ gelling systems composed of gellan gum alone and in combination with xanthan gum, HPMC or carbopol. The nanoemulsion based in situ gels showed a significantly sustained drug release in comparison to the nanoemulsion. Gellan/xanthan and gellan/HPMC possessed good stability at all studied temperatures, but gellan/carbopol showed partial drug precipitation upon storage and was therefore excluded from the study. Gellan/xanthan and gellan/HPMC showed higher therapeutic efficacy and more prolonged intraocular pressure lowering effect relative to that of commercial eye drops and oral tablet. Gellan/xanthan showed superiority over gellan/HPMC in all studied parameters and is thus considered as a promising mucoadhesive nanoemulsion-based ion induced in situ gelling formula for topical administration of acetazolamide.

Injectable and thermally contractible hydroxypropyl methyl cellulose/Fe3O4 for magnetic hyperthermia ablation of tumors.

The development of efficient strategies for the magnetic hyperthermia ablation of tumors remains challenging. To overcome the significant safety limitations, we developed a thermally contractible, injectable and biodegradable material for the minimally invasive and highly efficient magnetic hyperthermia ablation of tumors. This material was composed of hydroxypropyl methyl cellulose (HPMC), polyvinyl alcohol (PVA) and Fe3O4. The thermal contractibility of HPMC/Fe3O4 was designed to avoid damaging the surrounding normal tissue upon heating, which was confirmed by visual inspection, ultrasound imaging and computed tomography (CT). The efficient injectability of HPMC/Fe3O4 was proven using a very small needle. The biosafety of HPMC/Fe3O4 was evaluated by MTT and biochemical assays as well as flow cytometry (FCM). All the aforementioned data demonstrated the safety of HPMC/Fe3O4. The results of in vitro and ex vivo experiments showed that the temperature and necrotic volume of excised bovine liver were positively correlated with the HPMC/Fe3O4 weight, iron content and heating duration. The in vivo experimental results showed that the tumors could be completely ablated using 0.06 ml of HPMC/60%Fe3O4 after 180 s of induction heating. We believe that this novel, safe and biodegradable material will promote the rapid bench-to-bed translation of magnetic hyperthermia technology, and it is also expected to bring a new concept for the biomaterial research field.

Caffeic acid loading wound dressing: physicochemical and biological characterization.

AIM: Caffeic acid has been described as active against bacteria commonly isolated from wound infections. However, its low stability and poor solubility reduce caffeic acid applicability as a pharmaceutical product. These parameters can be enhanced by complexation with cyclodextrin. The main goal of the present work was to incorporate caffeic acid on cyclodextrin-based hydrogels capable of controlled delivery, in order to be used as antibacterial wound dressing. MATERIALS & METHODS: Cyclodextrin-based hydrogels were prepared by direct crosslinking of ß-cyclodextrin or hydroxypropyl-ß-cyclodextrin with 1,4-butanediol diglycidyl ether in the presence of hydroxypropyl methylcellulose. RESULTS: The hydrogels obtained combine good physicochemical properties (viscoelasticity, superabsorbency and high ability to retain and deliver caffeic acid) with the preservation of caffeic acid' antibacterial activity and effect on fibroblasts, with gel-ß-cyclodextrin the most suited. CONCLUSION: The hydrogels obtained could be useful as caffeic acid delivery-system devices for the treatment of wound infections.

Prevention of peritoneal adhesions using polymeric rheological blends.

The effectiveness of rheological blends of high molecular weight hyaluronic acid (HA) and low molecular weight hydroxypropyl methylcellulose (HPMC) in the prevention of peritoneal adhesions post-surgery is demonstrated. The physical mixture of the two carbohydrates increased the dwell time in the peritoneum while significantly improving the injectability of the polymer compared with HA alone. HA-HPMC treatment decreased the total adhesion area by ∼ 70% relative to a saline control or no treatment in a repeated cecal injury model in the rabbit. No significant cytotoxicity and minimal inflammation were associated with the blend. Furthermore, no chemical or physical processing was required prior to their use beyond simple mixing.