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Background Simvastatin (SMV), a hypocholesterolemic agent, suffers from very low bioavailability due to its poor aqueous solubility and extensive first-pass metabolism. Methods Two SMV carrier systems, namely, polymeric drug inclusion complex (IC) and mixed micelles (MM) nanoparticles, were developed and loaded into mucoadhesive buccal films to enhance SMV bioavailability. The two carrier systems were characterized and their permeation across human oral epithelial cells (OEC) was studied. The effect of IC to MM ratio (X1) and the mucoadhesive polymer concentration (X2) on the cumulative percent of drug released, elongation percent and the mucoadhesive strength, from the prepared mucoadhesive films, were optimized. Ex vivo permeation across bovine mucosal tissue was investigated. The permeation parameters for the in vitro and ex vivo release data were calculated. Results Complexation of SMV with hydroxypropyl beta-cyclodextrin (HP β-CD) was superior to all other polymers as revealed by the equilibrium saturation solubility, stability constant, complexation efficiency and thermodynamic potential. SMV-HP β-CD IC was utilized to develop a saturated polymeric drug solution. Both carrier systems showed enhanced permeation across OEC when compared to pure drug. X1 and X2 were significantly affecting the characteristics of the prepared films. The optimized mucoadhesive buccal film formulation loaded with SMV IC and drug MM nanoparticles demonstrated superior ex vivo permeation when compared to the corresponding pure drug buccal film, and the calculated permeation parameters confirmed this finding. Conclusion Mucoadhesive buccal films containing SMV IC and drug MM can be used to improve drug bioavailability; however, additional pharmacokinetic and pharmacodynamic studies are required.

Febuxostat (FBX) is used to treat gout and chronic hyperuricemia. However, its bioavailability is moderate (49%) as a result of low solubility and first-pass metabolism. Therefore, the aim of our s...

Maintaining oral health helps to prevent periodontal inflammation and pain, which can progress into more detrimental issues if left untreated. Meloxicam (MX) is a commonly used analgesic for periodontal pain, but it can have adverse gastrointestinal effects and poor solubility. Therefore, this study aimed to enhance the solubility of MX by developing a self-nanoemulsifying drug delivery system (SNEDDS). Considering the anti-ulcer activity of peppermint oil (PO), it was added in a mixture with medium-chain triglyceride (MCT) to the MX-loaded SNEDDS formulation (MX-PO-SNEDDS). After optimization, MX-PO-SNEDDS exhibited a PO:MCT ratio of 1.78:1, surfactant mixture HLB value of 14, and MX:oil mix ratio of 1:15, a particle size of 47 ± 3 nm, stability index of 85 ± 4%, ex vivo Jss of 4 ± 0.6 μg/cm2min, and ulcer index of 1 ± 0.25 %. Then, orally flash disintegrating lyophilized composites (MX-SNELCs) were prepared using the optimized MX-PO-SNEDDs. Results reveal that MX-SNELCs had a wetting time of 4 ± 1 s and disintegration time of 3 ± 1 s with a high in vitro MX release of 91% by the end of 60 min. The results of pharmacokinetic studies in human volunteers further demonstrated that, compared to a marketed MX tablets, MX-SNELCs provided a higher Cmax, Tmax, and AUC and a relatively greater bioavailability of 152.97 %. The successfully developed MX-SNELCs were found to be a better alternative than the conventional tablet dosage form, thus indicating their potential for further development in a clinically acceptable strategy for managing periodontal pain.

Gout is the most familiar inflammatory arthritis condition caused by the elevation of uric acid in the bloodstream. Febuxostat (FBX) is the latest drug approved by the United States Food and Drug Administration (US FDA) for the treatment of gout and hyperuricemia. FBX is characterized by low solubility resulting in poor gastrointestinal bioavailability. This study aimed at improving the oral bioavailability of FBX by its incorporation into self-nanoemulsifying delivery systems (SNEDS) with minimum globule size and maximum stability index. The SNEDS-incorporated FBX was loaded into a carrier substrate with a large surface area and lyophilized with other excipients to produce a fluffy, porous-like structure tablet for the transmucosal delivery of FBX. The solubility of FBX was studied in various oils, surfactants, and cosurfactants. Extreme vertices design was utilized to optimize FBX-SNEDS, and subsequently loaded into lyophilized tablets along with suitable excipients. The percentages of the main tablet excipients were optimized using a Box&ndash, Behnken design to develop self-nanoemulsifying lyophilized tablets (SNELTs) with minimum disintegration time and maximum drug release. The pharmacokinetics parameters of the optimized FBX-SNELTs were tested in healthy human volunteers in comparison with the marketed FBX tablets. The results revealed that the optimized FBX-SNELTs increased the maximum plasma concentration (Cmax) and decreased the time to reach Cmax (Tmax) with a large area under the curve (AUC) as a result of the enhanced relative oral bioavailability of 146.4%. The significant enhancement of FBX bioavailability is expected to lead to reduced side effects and frequency of administration during the treatment of gout.

Nanosuspensions are widely reported to enhance the solubility of poorly soluble drugs. In addition to enhancement in solubility, improvement of stability and therapeutic efficacy would be an added advantage. In the present study, premilling and subsequent high-pressure homogenization were carried out to produce naringenin nanosuspension. Hydroxypropyl methylcellulose and sodium dodecyl sulfate were evaluated for their performance as stabilizers under various homogenization cycles. The prepared nanosuspensions were studied for average particle size and size distribution, zeta potential, solubility, drug release, antioxidant activity, and in vitro antitumor activity. It was observed that both hydroxypropyl methylcellulose-stabilized nanosuspension and sodium dodecyl sulfate-stabilized nanosuspension produced an enhancement in physical stability, antioxidant potential, and in vitro cytotoxicity compared with naringenin. Furthermore, hydroxypropyl methylcellulose-stabilized nanosuspension was found to be better than sodium dodecyl sulfate-stabilized nanosuspension in terms of particle size and size distribution, storage stability, and drug release. This study showed that nanosuspension formulations could be a potential strategy for improving dissolution and antitumor activity of naringenin.

Pancreatic cancers are mostly inoperable and have a low survival rate. Nanomedicine has provided some promise in overcoming some major hurdles in pancreatic cancer. Meanwhile, resveratrol (RESV) has been reported to be useful in pancreatic cancer therapeutics. Therefore, the purpose of the study was to develop SNEDDS formulation of RESV for therapeutic application in pancreatic cancer therapy. Capryol 90, Cremophor RH, and Transcutol P were selected as the oil, surfactant, and co-surfactant respectively after preliminary studies. From the pseudo-ternary phase diagram, the surfactant:co-surfactant mixture (Smix) ratio of 3:1 was found to be most suitable for the formulation of SNEDDS. A central composite rotatable design (CCRD) was employed for studying the effect of volumes of oil and Smix on PS and PDI of globules formed from the SNEDDS. For this purpose, the Oil:Smix ratio of 1:4 was chosen for the central point in the design. The results of CCRD showed that a higher volume of oils results in a higher PS and PDI. Similarly, a higher volume of Smix resulted in a lower PS and PDI. The SNEDDS formulation for characterization was chosen based on the particle size (PS), polydispersity index (PDI), and thermodynamic stability. The TEM images revealed uniformity in size and morphology of the formed droplets. Meanwhile, the in vitro RESV release was rapid from RESV-SNEDDS. The cell viability studies, change in mitochondrial membrane potential (MMP), COX-2 and NF-kB levels, and the wound scratch method showed enhanced cytotoxicity of RESV-SNEDDS compared to RESV alone. Overall, the formulation of RESV into SNEDSS was proved to be a promising approach for overcoming the therapeutic hindrances related to pancreatic cancer.

Children spend most of their daily time indoors. Many of the items used indoors, such as furniture, electronics, textile, and children toys, are treated with chemicals to provide longevity and fulfil the safety standards. However, many chemicals added to these products are released into the environment during leaching out from the treated products. Many studies have reported brominated flame retardants (BFRs) in indoor environments, however, few have focused on environments specified for young children. In this study, paired air (PM10) and dust samples were collected from the rooms (n = 30) of Saudi children. These samples were analyzed for different congeners of polybrominated diphenyl ethers (PBDEs) and three important alternative flame retardants using gas chromatography-mass spectrometry. Decabromodiphenyl ether (BDE 209) was the most important analyzed BFR in dust and PM10 samples with a median value of 3150 ng/g of dust and 75 pg/m3. This indicates the wider application of BDE 209 has implications for its occurrence, although its use has been regulated for specified uses since 2014. Among alternative BFRs, 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), Bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (TBPH), and 1,2-Bis(2,4,6-tribromophenoxy)ethane (BTBPE) were found with a median levels of 10, 15 and 8 ng/g of dust, respectively. However, alternative BFRs were present in &lt, 50% of the PM10 samples. The calculated long term and daily exposures via indoor dust and PM10 of Saudi children from their rooms were well below the respective reference dose (RfD) values. Nonetheless, the study highlights BDE 209 at higher levels than previously reported from household dust in Saudi Arabia. The study warrants further extensive research to estimate the different classes of chemical exposure to children from their rooms.

Conventional treatments for common disorders of the oral mucous membranes have great challenges, and this has motivated the development of local therapeutics with an advanced delivery platform. The present study aimed to develop a hydrogel containing clotrimazole‒rosehip oil nanoethosomes (CZ-RO-NE) and to evaluate its antibacterial and antifungal efficacy and ulcer index. Optimization of CZ-RO-NE was performed by the Box‒Behnken statistical design using l -α-phosphatidylcholine, CZ, and RO as independent variables. The optimized formulations were characterized for their rheological properties, in vitro release characteristics, and ex vivo permeability. An optimized formulation was fabricated using the thin-layer evaporation technique where the rheological property indicated non-Newtonian flow. The in vitro release profile of the formulations showed a significantly higher release (80 ± 6.723%) from the CZ-RO-NE‒embedded hydrogel compared with the marketed formulation and drug suspension (p

Ciprofloxacin (Cf) is antibiotic used oculary for treatment of conjunctivitis and corneal ulcers. The barriers for its use are: high dosage frequency and poor solubility lead to ocular irritation. This study sought to develop ciprofloxacin-cubosomal (Cf-Cub) in situ gel in order to improve eye permeation, prolong the ocular retention time, and enhance its antimicrobial activity. Box-Behnken design was used to prepare cubosomes. Three independent variables were; Phytantriol amount, Lutrol amount, and hydration media pH, while particle size, encapsulation, and steady state flux were evaluated as dependent variables. The optimised cubosomes were evaluated for antimicrobial activity, and in vivo estimation of Cf in the aqueous humour of rabbits’ eyes. The results indicated that, the optimised formula consisted of 60 mg of Cf, 100 mg phytantriol, 25 mg Lutrol, and hydration media pH equal 5.8 produced cubosomes with 121 nm size, 75% entrapment, and 2.54 times antimicrobial activity compared with commercially eye drops. The estimation of Cf in aqueous humour indicated that once daily administration of the optimised formula maintain the drug concentration above MIC compared with commercial drops which require four times daily administration. This confirmed that optimised formula improved eye permeation, prolonged the ocular retention time, and enhanced the antimicrobial activity.

The present investigation was undertaken to develop a statistically and optimized omega-3-phospholipid based nanotransfersomes [NTFs] loaded with Pravastatin sodium [PVS] and Naringin [NG] in order to reverse the PVS induced hepatic marker enzymes elevation, decrease lipid peroxidation, and enhance the anti-oxidant cascade. NTFs were developed by a modified thin-film hydration technique using omega-3- phospholipids and sodium deoxycholate. The composition of the NTFs was statistically optimized by the design of Experiments using Box–Behnken design with three factors at three levels. They were characterized for size, EE%, ex-vivo permeation, and in-vivo hepatic markers enzymes level estimation. Omega-3-phospholipid has the most prominent effect on the particle size, followed by sodium deoxycholate. However, EE [%] is mostly affected by sodium deoxycholate, followed by omega-3-phospholipid. The optimized NTFs showed particle size, EE%, and cumulative % permeation of 191 nm, 76% and 55% respectively. The in-vivo study of optimized formulation revealed that NG act synergistically with omega-3-phospholipids, and potentially reverse the hepatic marker enzymes [ALT], and lipid peroxidative markers [MDA] induced by PVS to 54 IU/L and 45 mmol/mg protein respectively.