Exploration of Cassia fistula L. seed mucilage into floating drug delivery system.

The aim of the present study was to explore Cassia fistula L. seed mucilage as a natural polymer in controlled release floating drug delivery system. First, seed mucilage was extracted and evaluated for phytochemical screening, solubility studies, swelling index, viscosity and surface tension. Then, Atenolol floating systems were prepared with and without the C. fistula L. seed mucilage by direct compression method. Phytochemical screening resulted from the presence of secondary metabolite carbohydrates, glycosides, flavonoids and phenolic compounds in good amounts. Results of hardness, friability, drug content and swelling index were satisfactory. The floating behaviour can increase the gastric residence time and eventually improve the bioavailability of the drug as evidence from in vitro buoyancy and dissolution studies. Interestingly, developed floating system showed remarkable increase in dissolution. Conclusively, the results suggest that developed Atenolol floating system with C. fistula L. seed mucilage demonstrate interesting attributes to be explored for potential pharmaceutical application.

Pazopanib-laden lipid based nanovesicular delivery with augmented oral bioavailability and therapeutic efficacy against non-small cell lung cancer.

The present investigation deals with the pazopanib-loaded solid lipid nanoparticles (Pazo-SLNs) and their in-vitro and in-vivo assessments. Quality by design approach employing the Plackett-Burman and central composite design was used to identify the formulation variables, including drug/lipid ratio, organic/aqueous phase ratio, and surfactant concentration with a significant impact on the process and to fabricate a safe and efficacious novel oral dosage form of pazopanib. Particle size, drug loading, entrapment efficiency, and zeta potential of optimal Pazo-SLNs formulation were 210.03 ± 7.68 nm, 13.35 ± 0.95 %, 79.05 ± 2.55 % and -18.29 ± 1.89 mV (n = 3) respectively. FTIR study affirmed the absence of incompatibilities between the drug and the excipients. DSC and XRD measurements substantiated the amorphous form of pazopanib entrapped within the SLNs. Pazo-SLNs demonstrated high cellular uptake, showed substantial cytotoxicity to A-549 lung cancer cells due to apoptotic mode and inhibited tyrosine kinase in-vitro. Pazo-SLNs were found to be stable for three months. SLNs greatly ameliorated the pharmacokinetic behavior and bioavailability (9.5 folds) of pazopanib with a sustained-release pattern (92.67 ± 4.68 % within 24 h). A biodistribution study corroborated the lung targeting potential of Pazo-SLNs. Thus, SLNs could potentially boost the oral route efficacy of pazopanib against cancer cells.

Capsaicin Loaded Solid SNEDDS for Enhanced Bioavailability and Anticancer Activity: In-Vitro, In-Silico, and In-Vivo Characterization.

In this investigation, the fabrication of capsaicin loaded self nano emulsifying drug delivery system (SNEDDS) was attempted to improve the effectiveness of capsaicin through the oral route. A pseudo-ternary phase diagram was constructed at different km values (1:1, 2:1, & 3:1). Nine liquid formulations (L-CAP-1 to L-CAP-9) were prepared at km = 3, evaluated & converted to solid free-flowing granules using neusilin® US2. L-CAP-3 comprising of 15% isopropyl myristate, 33.75% Labrafil, & 11.25% ethanol exhibited higher % transmittance (98.90 ± 1.24%) & lower self-emulsification time (18.19 ± 0.46 s). FT-IR spectra showed no incompatibility whereas virtual analysis confirmed hydrogen bond interaction between amino hydrogen in the capsaicin & oxygen of the neusilin. DSC & XRD study revealed the amorphization & molecular dispersion of capsaicin in S-SNEDDS. TEM analysis confirmed the nano-sized spherical globules. Within 15 min, L-SNEDDS, S-SNEDDS, & pure capsaicin showed 87.36 ± 3.25%, 85.19 ± 4.87%, & 16.61 ± 3.64% drug release respectively. S-CAP-3 significantly (P < 0.001) inhibited the proliferation of HT-29 colorectal cancer cells than capsaicin. Apoptosis assay involving Annexin V/PI staining for S-CAP-3 treated cells demonstrated a significant (P < 0.001) apoptotic rate. Remarkably, 3.6 fold increase in bioavailability was observed after oral administration of capsaicin-SNEDDS than plain capsaicin.

Nanoliposome Precursors for Shape Modulation: Use of Heuristic Algorithm and QBD Principles for Encapsulating Phytochemicals.

BACKGROUND: Screening of multiple methods is worthless for formulators due to material losses, wastage of time, and expenditures. It is imperative to make a quick decision. OBJECTIVE: The present investigation describes the systematic approach to select the best suitable method for the development of nanoliposomes (NL), the precursor of nanocochleates encapsulating curcumin using Analytic Hierarchy Process (AHP). METHODS: Pair-wise comparison matrices were used to achieve the overall priority weight and ranking for the selection of appropriate technique. Furthermore, Plackett-Burman screening Design (PBD) was exploited to investigate specific effects of associated formulation and process variables on particle size (Y1), drug content (Y2), and entrapment efficiency (Y3), while fabricating NL. RESULTS: Results revealed the reliability of the pair-wise comparison matrices and selected the ethanol injection method with the highest priority weight (0.337). Bland-Altman plot and control chart validated the results of AHP. The preparation of vesicles with the preferred diameter and size distribution was essentially fulfilled. Stirring speed (X5), amount of phospholipid (X4), and cholesterol (X8) showed significant influence (p<0.05;) on Y1 and Y3, PBD revealed. These factors can be further optimized using the design of experiments. CONCLUSION: AHP being an effective tool, has assisted in selecting the best alternative for fabricating NL, whilst PBD enabled a clear understanding of the effects of diverse formulation variables on responses studied. Results ensure that NL is a riveting candidate for modulating effectively into tailormade diverse shaped nanoformulations for further in vitro; and in vivo; studies.

Acrylamide grafted neem (Azadirachta indica) gum polymer: Screening and exploration as a drug release retardant for tablet formulation.

The study was initiated with the intent to synthesize acrylamide grafted neem gum polymer (AAm-g-NG), and screen its drug release retardation ability both in vitro and in vivo. Different batches (NGP-1 to NGP-9) of tablet formulation were prepared by varying polymer concentration using propranolol HCl and compared with HPMC K100 M and marketed SR tablets. FTIR study proved the grafting phenomenon and showed no incompatibility between AAm-g-NG and propranolol HCl. AAm-g-NG showed significant swelling and water retention capacity than NG. AAm-g-NG was found to be biodegradable and exhibited no toxicity to Artemia salina. After 12 h, NGP-6 showed non-significant (p > 0.05; f2= ∼ 90) percent drug release (80.52 ±â€¯3.41%) compare to marketed formulation (79.65 ±â€¯4.08%). Significant swelling of the matrix caused slower diffusion of the drug. NGP-6 and marketed formulation in rabbits showed the non-significant difference between Cmax and Tmax, hence NGP-6 meets the requirement of sustained-release tablets.

Isolation, characterization, and evaluation of Cassia fistula Linn. seed and pulp polymer for pharmaceutical application.

INTRODUCTION: Present work, is an effort toward exploring the potential of Cassia fistula Linn. seed gum as an extended release polymer and laxative. While, C. fistula pulp polymer has evaluated as suspending agent. MATERIALS AND METHODS: For extended release application, total five batches (F1-F5) were prepared by varying the ratio of drug:polymer as 1:1, 1:2, 1:3, 1:4, and 1:5, respectively. The granules were prepared by wet granulation method and further evaluated for micromeritic properties such as angle of repose (θ), Carr's compressibility index (CCI), and Hausner's ratio. Further compacts were evaluated by hardness, thickness, swelling index, in-vitro dissolution, and so on. Laxative activity was evaluated by administration of seed polymer (100 mg/kg) alone or in combination with bisacodyl (2.5 mg/kg) in 1% Tween 80. Zinc oxide suspension was prepared by varying the concentration of C. fistula pulp polymer and compared with suspension made by use of tragacanth, sodium carboxymethyl cellulose and bentonite. RESULTS: Result showed that granules were free flowing, while the compact extended the drug release up to 10 h (72.84 ± 0.98; batch F5) and followed Higuchi matrix release kinetics. This extended release might be due to the formation of polyelectrolyte complex because of gluco-mannose in seed gum. Result of in-vivo laxative activity showed that seed polymer reduced faeces weight after 24 h compared to control (P < 0.01). CONCLUSIONS: Pulp polymer showed good sedimentation volume, but alone fails to stabilize the suspension for a longer period, so it could be useful in combination with other suspending agents and can be useful as novel excipient.

Solid-state characterization and dissolution properties of meloxicam-moringa coagulant-PVP ternary solid dispersions.

The effect of ternary solid dispersions of poor water-soluble NSAID meloxicam with moringa coagulant (obtained by salt extraction of moringa seeds) and polyvinylpyrrolidone on the in vitro dissolution properties has been investigated. Binary (meloxicam-moringa and meloxicam-polyvinylpyrrolidone (PVP)) and ternary (meloxicam-moringa-PVP) systems were prepared by physical kneading and ball milling and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffractometry. The in vitro dissolution behavior of meloxicam from the different products was evaluated by means of United States Pharmacopeia type II dissolution apparatus. The results of solid-state studies indicated the presence of strong interactions between meloxicam, moringa, and PVP which were of totally amorphous nature. All ternary combinations were significantly more effective than the corresponding binary systems in improving the dissolution rate of meloxicam. The best performance in this respect was given by the ternary combination employing meloxicam-moringa-PVP ratio of [1:(3:1)] prepared by ball milling, with about six times increase in percent dissolution rate, whereas meloxicam-moringa (1:3) and meloxicam-PVP (1:4) prepared by ball milling improved dissolution of meloxicam by almost 3- and 2.5-folds, respectively. The achieved excellent dissolution enhancement of meloxicam in the ternary systems was attributed to the combined effects of impartation of hydrophilic characteristic by PVP, as well as to the synergistic interaction between moringa and PVP.