Effect of dry heat and its combination with vacuum heat on physicochemical, rheological and release characteristics of Alocasia macrorrhizos retrograded starches.

Retrograded starches have received increasing attention due to their potential excipient properties in pharmaceutical formulations. However, to evade its application-oriented challenges, modification of retrograded starch is required. The study emphasizes influence of dry heating and the dual heat treatment by dry heating amalgamation with the vacuum heat treatment on quality parameters of retrograded starch. The starch was isolated by using two different extraction media (0.05 % w/v NaOH and 0.03 % citric acid) from Alocasia macrorrhizos and then retrograded separately. Further, retrograded starches were first modified by dry heating and afterwards modified with combination of dry and vacuum heating. Modification decreased moisture, ash content and increased solubility. Modified Samples from NaOH media had higher water holding capacity and amylose content. X-ray diffraction revealed type A and B crystals with increasing crystallinity of retrograded heat-modified samples from NaOH media. Thermogravimetric analysis, differential scanning calorimetry confirmed thermal stability. Shear tests showed shear-thinning behavior whereas dominant storage modulus (G/) over loss modulus (G//), depicting gel-like behavior. Storage, loss, and complex viscosity initially increased, then decreased with temperature. In-vitro release reflects, modified retrograded starches offers versatile drug release profiles, from controlled to rapid. Tailoring starch properties enables precise drug delivery, enhancing pharmaceutical formulation flexibility and efficacy.

Impact of nanocarrier aggregation on EPR-mediated tumor targeting.

The aim of this study was to investigate the influence of excipients on retaining the particle size of methotrexate (MTX) loaded chitosan nanocarriers (CsNP) during lyophilization, which relates to the ability to enlarge the particle size and target specific areas. The nanocarriers were prepared using the ionic gelation technique with tripolyphosphate as a crosslinker. Three lyophilized formulations were used: nanosuspension without Lyoprotectant (NF), with mannitol (NFM), and with sucrose (NFS). The lyophilized powder intended for injection (PI) was examined to assess changes in particle size, product integrity, and comparative biodistribution studies to evaluate targeting ability. After lyophilization, NFS was excluded from in-vivo studies due to the product melt-back phenomenon. The particle size of the NF lyophile significantly increased from 176 nm to 261 nm. In contrast, NFM restricted the nanocarrier size to 194 nm and exhibited excellent cake properties. FTIR, XRD, and SEM analysis revealed the transformation of mannitol into a stable ß, δ polymorphic form. Biodistribution studies showed that the nanocarriers significantly increased MTX accumulation in tumor tissue (NF = 2.04 ± 0.27; NFM = 2.73 ± 0.19) compared to the marketed PI (1.45 ± 0.25 µg), but this effect was highly dependent on the particle size. Incorporating mannitol yielded positive results in restricting particle size and favoring successful tumor targeting. This study demonstrates the potential of chitosan nanocarriers as promising candidates for targeted tumor drug delivery and cancer treatment.

23 Full Factorial Model for Particle Size Optimization of Methotrexate Loaded Chitosan Nanocarriers: A Design of Experiments (DoE) Approach.

PURPOSE: To build and inquire a statistically significant mathematical model for manufacturing methotrexate loaded chitosan nanoparticles (CsNP) of desired particle size. The study was also performed to evaluate the effect of formulation variables in the explored design space. METHOD: Ionotropic gelation technique was followed for chitosan nanocarriers by changing formulation variables suggested as per Design Expert software. Altering the levels of Chitosan, tripolyphosphate, methotrexate by 23 factorial design served the purpose. The CsNP were characterized for nanocarrier formation, particle size, and statistical analysis. Then mathematical model was statistically analyzed for fabricating desired formulation having particle size less than 200nm. RESULTS: FT-IR, XRD reports confirmed the structural change in chitosan which lead to the formation of CsNP. For particle size, linear model was found to be best fit to explain effect of variables. Besides, high R2 (0.9958) defends the constancy of constructed model. Chitosan exhibited higher t-value in Pareto chart and a p-value <0.0001. Based on maximum desirability, optimization was performed and amount of variables for preparing CsNP of 180nm was predicted. The experiment was carried out with software suggested combination and particle size was found to be 176±4nm. CONCLUSION: Low p-value endorsed the greater dominance of chitosan on particle size. Good model adequacy and small percentage error between predicted and experimented value established the reliability of constructed model for robust preparation of CsNP.

Development and evaluation of nefopam transdermal matrix patch system in human volunteers.

Nefopam hydrochloride, a nonsteroidal anti-inflammatory drug, is administered in tablet form three times daily or as intramuscular injection at 6-h intervals to treat disorders such as acute or constant pain. It is also used for a prolonged treatment of severe pain, when morphine therapy has to be withdrawn for morphine-related dependence. To achieve a constant drug-plasma level of nefopam for a prolonged period, a transdermal drug delivery system was fabricated in our present study by employing suitable experimental hydrophilic and lipophilic polymeric combinations of polyvinyl pyrrolidone (PVP) and ethyl cellulose (EC). Physical studies including weight variation, moisture content, moisture uptake, flatness, external morphology of the formulations, and in vitro drug release were performed. Drug-excipient interaction studies were carried out using Fourier transform infrared spectroscopy. In vitro skin permeation study with cadaver skin was conducted using modified Keshary-Chein diffusion cells. Interactions between nefopam and PVP seem to contribute to the slow and controlled release pattern of nefopam. The scanning electron microscopy evaluation of prepared matrix patches revealed that drug was dispersed uniformly in polymeric matrix. In vitro drug release study showed that an increase in concentration of hydrophilic polymer, PVP, enhanced drug release substantially. In vitro skin permeation study showed variable permeation profiles of nefopam from the experimental patches. Among the formulations, PVP:EC (1:3) was found to provide slowest release and maximum sustained skin permeation of drug in vitro. Application of those patches, PVP:EC (1:3), on human volunteers was found to provide systemic availability of the drug till 48 h.