Dasatinib Nanoemulsion and Nanocrystal for Enhanced Oral Drug Delivery

In this work, dasatinib (DAS) nanoemulsion and nanocrystal are produced by high-gravity technology that approaches to practical mass production. The drug nanoformulations were systematically characterized and evaluated. At a low high-gravity level (β) = 47, nanoemulsion droplets were 16.15 ± 0.42 nm with a PDI of 0.122 ± 0.021. The nanoemulsion’s size and active pharmaceutical ingredient (API) content remained stable at long-term (4 months) freeze–thaw and dilution experiments. At a high β = 188, the as-prepared nanocrystal was lamellar with a short diameter of about 200 nm and a long diameter of about 750 nm. In vitro performances demonstrated the nanoemulsion displayed higher cytotoxicity on MDA-MB-231 tumor cells, Caco-2 cell permeability and drug release than that of the nanocrystal, indicating that nanoemulsion should be an ideal alternative for dasatinib oral administration.

A Novel Approach to Configuration Redesign: Using Multiobjective Monotonicity Analysis to Alter the Pareto-set

Configuration (or topology or embodiment) design remains a ubiquitous challenge in product design optimization and in design automation, meaning configuration design is largely driven by experience in industrial practice. In this article, we introduce a novel configuration redesign process founded on the interaction of the designer with results from rigorous multiobjective monotonicity analysis. Guided by Pareto-set dependencies, the designer seeks to reduce trade-offs among objectives or improve optimality overall, deriving redesigns that eliminate dependencies or relax active constraints. The method is demonstrated on an ingestible medical device for oral drug delivery, currently in early concept development.

Scrutinizing the Feasibility of Nonionic Surfactants to Form Isotropic Bicelles of Curcumin: a Potential Antiviral Candidate Against COVID-19

Investigating bicelles as an oral drug delivery system and exploiting their structural benefits can pave the way to formulate hydrophobic drugs and potentiate their activity. Herein, the ability of non-ionic surfactants (labrasol®, tween 80, cremophore EL and pluronic F127) to form curcumin loaded bicelles with phosphatidylcholine, utilizing a simple method, was investigated. Molecular docking was used to understand the mechanism of bicelles formation. The % transmittance and TEM exhibited bicelles formation with labrasol® and tween 80, while cremophor EL and pluronic F127 tended to form mixed micelles. The surfactant-based nanostructures significantly improved curcumin dissolution (99.2 ± 2.6% within 10 min in case of tween 80-based bicelles) compared to liposomes and curcumin suspension in non-sink conditions. The prepared formulations improved curcumin ex vivo permeation over liposomes and drug suspension. Further, the therapeutic antiviral activity of the formulated curcumin against SARS-CoV-2 was potentiated over drug suspension. Although both Labrasol® and tween 80 bicelles could form bicelles and enhance the oral delivery of curcumin when compared to liposomes and drug suspension, the mixed micelles formulations depicted superiority than bicelles formulations. Our findings provide promising formulations that can be utilized for further preclinical and clinical studies of curcumin as an antiviral therapy for COVID-19 patients.

A Review on Recent Controlled Release Strategies for Oral Drug Delivery of Repaglinide (a BCS Class II Drug)

: Repaglinide is an antidiabetic drug that works by stimulating insulin secretion from pancreatic beta cells. Repaglinide is practically insoluble in water with a water solubility of 34 µg/mL at 37 ˚C, and it has a high absorption rate from the gastrointestinal tract following oral administration since the log P value of repaglinide is 3.97. The low aqueous solubility and the high permeability of repaglinide represent a typical behavior for drugs that belong to class II Biopharmaceutical Classification System (BCS II). Managing type-2 diabetes mellitus with repaglinide is considered a burdensome therapy, as it requires frequent dosing of repaglinide before each meal to maintain its therapeutic plasma concentration due to its short plasma half-life of approximately one hour. Hence the present review aims to discuss thoroughly the various approaches investigated in recent years to develop drug delivery systems that improve oral delivery of repaglinide, including nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, sustained-release hydrophilic matrix, floating microspheres, and nanocomposites.

A Comprehensive Review on Mouth Dissolving Tablet

Oral drug delivery system of Mouth Dissolving Tablets (MDTs) is using a new concept that have been mostly accepted in the pharmaceutical industry in recent days. This system is the most comfortable, safest and inexpensive of drug delivery system, enhancing the patient compliance and extending the patient life. Mouth dissolving formulations using an important ingredient or active agent due to allow release of drug is rapidly after that produce faster dissolution process. The mouth dissolving tablets contain a unique property of tablets like quickly disintegrating or easily dissolving and releasing the active drug within a few minutes and its contact with saliva. In pediatric, geriatric, bed ridden, psychic, dysphagic patients are using the MDTs because of these tablets are easily engulfing or swallowing is most convenient and patient compliance is better to compared than other Delivery systems. The tablets are formulated with an aid of super disintegrant. It's more reliable because of better compliance in patients. There are several technologies used in the MDTs manufacturing process such as patented technology & conventional technology. The important patented technologies are Durasolve Technology, Orasolve Technology, Zydis Technology, Wow Tab Technology, Flash Dose Technology, Flash Tab Technology and Quick Solv Technology. The MDTs are improving the demand for rapidly growing areas in the pharmaceutical industry and other fields are also in demand on these formulations. The recent progress of pharmaceutical fields is allowing the improvement of a better route of health care management with avoidance of numerous difficulties are connected to the other Drug Delivery System (DDS).

FORMULATION AND EVALUATION OF MEDICATED TENOFOVIR ALAFENAMIDE FUMARATE CANDY FOR TREATMENT OF HUMAN IMMUNODEFICIENCY SYNDROME

Medicated candies are solid oral dosage form containing medicaments in a flavored and sweetened base. The main advantages associated with buccal drug delivery are systemic absorption of drug, also increased bioavailability and avoidance of hepatic first pass metabolism. Tenofovir alafenamide fumarate is a drug of choice for the treatment of human immunodeficiency virus due to its potency and fewer side effects over tenofovir disoproxil fumarate. The aim of the present research work was to formulate and evaluate candy of tenofovir alafenamide fumarate for pediatric and geriatric patients for better patient acceptability. Medicated candies of tenofovir alafenamide fumarate were prepared by using heating and congealing method, and the prepared formulations were evaluated for various parameters such as organoleptic properties, weight variation, friability, hardness, drug content and in vitro drug dissolution time profile. On the basis of the above studies, it can be concluded that medicated candy can be utilized as alternative option for oral drug delivery for pediatric and geriatric patients.

Formulation of Lipid-Based Tableted Spray-Congealed Microparticles for Sustained Release of Vildagliptin: In Vitro and In Vivo Studies

Spray-congealing (SPC) technology was utilized to prepare lipid-based microparticles (MP) capable of sustaining the release of Vildagliptin (VG) for use as a once-daily treatment for type 2 diabetes mellitus. VG microparticles were prepared using Compritol® and Gelucire®50/13 as lipid carriers in the presence of various amounts of Carbomer 934 NF. The lipid carriers were heated to 10 °C above their melting points, and VG was dispersed in the lipid melt and sprayed through the heated two-fluid nozzle of the spray congealer to prepare the VG-loaded MP (VGMP). The microparticles produced were then compressed into tablets and characterized for their morphological and physicochemical characteristics, content analysis, in vitro dissolution, and in vivo bioavailability studies in mixed-breed dogs. The VGMP were spherical with a yield of 76% of the total amount. VG was found to be in its semicrystalline form, with a drug content of 11.11% per tablet and a percentage drug recovery reaching 98.8%. The in vitro dissolution studies showed that VG was released from the tableted particles in a sustained-release fashion for up to 24 h compared with the immediate-release marketed tablets from which VG was completely released within 30 min. The in vivo pharmacokinetics studies reported a Cmax, Tmax, T1/2, and MRT of 118 ng/mL, 3.4 h, 5.27 h, and 9.8 h, respectively, for the SPC formulations, showing a significant difference (p < 0.05)) from the pk parameters of the immediate-release marketed drug (147 ng/mL, 1 h, 2.16 h, and 2.8 h, respectively). The area under the peak (AUC) of both the reference and tested formulations was comparable to indicate similar bioavailabilities. The in vitro–in vivo correlation (IVIVC) studies using multiple level C correlations showed a linear correlation between in vivo pharmacokinetics and dissolution parameters. In conclusion, SPC was successfully utilized to prepare a once-daily sustained-release VG oral drug delivery system.