Due to its extreme lipophilicity, the oral delivery of cinnarizine (CN) encounters several problems such as poor aqueous solubility and pH-dependent dissolution, which result in low and erratic bioavailability The current study aims to design self-nanoemulsifying drug delivery systems (SNEDDS) of CN that circumvent such obstacles Equilibrium solubility of CN was determined in a range of anhydrous and diluted lipid-based formulations Dynamic dispersion tests were carried out to investigate the efficiency of drug release and magnitude of precipitation that could occur upon aqueous dilution Droplet sizes of selected formulations, upon (1:1,000) aqueous dilution, were presented The optimal formulations were enrolled in subsequent dissolution studies The results showed that increasing lipid chain length and surfactant lipophilicity raised the formulation solvent capacity, while adding co-solvents provoked a negative influence The inclusion of mixed glycerides and/or hydrophilic surfactants improved the drug release efficiency Generally, no significant precipitation was observed upon aqueous dilution of the formulations Five formulations were optimal in terms of their superior self-emulsifying efficiency, drug solubility, dispersion characteristics, and lower droplet size Furthermore, the optimal formulations showed superior dissolution profile compared to the marketed (Stugeron®) tablet Most importantly, they could resist the intensive precipitation observed with the marketed tablet upon shifting from acidic to alkaline media However, SNEDDS containing medium-chain mixed glycerides showed the highest drug release rate and provide great potential to enhance the oral CN delivery Accordingly, the lipid portion seems to be the most vital component in designing CN self-nanoemulsifying systems

/pdf/novel-self-nanoemulsifying-drug-delivery-systems-snedds-for-54569ke1r8.pdf

Novel Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Oral Delivery of Cinnarizine: Design, Optimization, and In-Vitro Assessment

Oral bioavailability of cinnarizine in dogs: relation to SNEDDS droplet size, drug solubility and in vitro precipitation.

To circumvent the low and erratic absorption of orally administrated cinnarizine (CN), intranasal lyophilized gels containing unsaturated fatty acid liposomes (ufasomes) and encapsulating CN were prepared from oleic acid using a simple assembling strategy. The effects of varying drug concentration and cholesterol percentage on ufasomes size, polydispersity index and entrapment efficiency were investigated using 3141 full factorial design. The optimized ufasomes that contained 14% cholesterol relative to oleic acid displayed spherical morphology with average size of 788 nm and entrapment efficiency of 80.49%. To overcome the colloidal instability of CN-loaded ufasomes dispersions and their short residence time in the nasal cavity, the ufasomes were incorporated into mucoadhesive hydrogels that were lyophilized into unit dosage forms for accurate dosing. Scanning electron micrographs of the lyophilized gel revealed that the included ufasomes were intact, non-aggregating and maintained their spherica...

Ufasomes nano-vesicles-based lyophilized platforms for intranasal delivery of cinnarizine: preparation, optimization, ex-vivo histopathological safety assessment and mucosal confocal imaging

Low solubility causing low dissolution in gastrointestinal tract is the major problem for drugs meant for systemic action after oral administration, like cinnarizine. Pharmaceutical products of cinnarizine are commercialized globally as immediate release preparations presenting low absorption with low and erratic bioavailability. Approaches to enhance bioavailability are widely cited in the literature. An attempt has been made to review the bioavailability complications and clinical therapeutics of poorly water soluble drug: cinnarizine. The interest of writing this paper is to summarize the pharmacokinetic limitations of drug with special focus on strategies to improvise bioavailability along with effectiveness of novel dosage forms to circumvent the obstacle. The paper provides insight to the approaches to overcome low and erratic bioavailability of cinnarizine by cyclodextrin complexes and novel dosage forms: self-nanoemulsifying systems and buoyant microparticulates. Nanoformulations need to systematically explored in future, for their new clinical role in prophylaxis of migraine attacks in children. Clinical reports have affirmed the role of cinnarizine in migraine prophylaxis. Research needs to be dedicated to develop dosage forms for efficacious bioavailability and drug directly to brain.

/pdf/recent-advances-in-delivery-systems-and-therapeutics-of-1lchcrgddn.pdf

Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach

Depth data with a predominance of discriminative power in location is advantageous for accurate salient object detection (SOD). Existing RGBD SOD methods have focused on how to properly use depth information for complementary fusion with RGB data, having achieved great success. In this work, we attempt a far more ambitious use of the depth information by injecting the depth maps into the encoder in a single-stream model. Specifically, we propose a depth injection framework (DIF) equipped with an Injection Scheme (IS) and a Depth Injection Module (DIM). The proposed IS enhances the semantic representation of the RGB features in the encoder by directly injecting depth maps into the high-level encoder blocks, while helping our model maintain computational convenience. Our proposed DIM acts as a bridge between the depth maps and the hierarchical RGB features of the encoder and helps the information of two modalities complement and guide each other, contributing to a great fusion effect. Experimental results demonstrate that our proposed method can achieve state-of-the-art performance on six RGBD datasets. Moreover, our method can achieve excellent performance on RGBT SOD and our DIM can be easily applied to single-stream SOD models and the transformer architecture, proving a powerful generalization ability.

Depth Injection Framework for RGBD Salient Object Detection.

Effect of route of administration on the pharmacokinetics and toxicokinetics of cinnarizine in dogs

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Effect of route of administration on the pharmacokinetics and toxicokinetics of cinnarizine in dogs