Search

Based on the administration convenience, transmucosal buccal drug delivery allows special strength points over peroral routes for systemic delivery. It could achieve local or systemic effect and boost drugs' bioavailability for agents with first pass metabolism. The current study aimed to manufacture and optimize a lavender oil-based nanoemulsion loaded with zaleplon and incorporate it into fast-disintegrating tablets to promote its dissolution and oral bioavailability via oral mucosa. Zaleplon-loaded nanoemulsions were devised with various levels of lavender oil (10% to 25%), the surfactant Sorbeth-20 (35% to 65%), and the co-surfactant HCO-60 (20% to 40%); the extreme vertices mixture statistical design was adopted. The droplet size and drug-loading efficiency were the evaluated. The optimal formulation was transformed into self-nanoemulsified lyophilized tablets (ZP-LV-SNELTs), which were tested for their uniformity of content, friability, and disintegration time with in-vitro release. Finally, the pharmacokinetic parameters of the ZP-LV-SNELTs were determined and compared with those of marketed formulations. The optimal nanoemulsion had a droplet size of 87 nm and drug-loading capacity of 185 mg/mL. ZP-LV-SNELTs exhibited acceptable friability and weight uniformity and a short disintegration time. The in-vitro release of ZP-LV-SNELTs was 17 times faster than that of the marketed tablet. Moreover, the optimal ZP-LV-SNELTs increased the bioavailability of zaleplon in rabbits by 1.6-fold compared with the commercial tablets. Hence, this investigation revealed that ZP-LV-SNELTs delivered zaleplon with enhanced solubility, a fast release, and boosted bioavailability thru oral mucosa which provided a favorable route for drug administration which is suggested to be clinically investigated in future studies.

Candida albicans is the fungus responsible for oral candidiasis, a prevalent disease. The development of antifungal-based delivery systems has always been a major challenge for researchers. This study was designed to develop a nanostructured lipid carrier (NLC) of sesame oil (SO) loaded with miconazole (MZ) that could overcome the solubility problems of MZ and enhance its antifungal activity against oral candidiasis. In the formulation of this study, SO was used as a component of a liquid lipid that showed an improved antifungal effect of MZ. An optimized MZ-loaded NLC of SO (MZ-SO NLC) was used, based on a central composite design-based experimental design; the particle size, dissolution efficiency, and inhibition zone against oral candidiasis were chosen as dependent variables. A software analysis provided an optimized MZ-SO NLC with a particle size of 92 nm, dissolution efficiency of 88%, and inhibition zone of 29 mm. Concurrently, the ex vivo permeation rate of the sheep buccal mucosa was shown to be significantly (p

Skin infection compromises the body’s natural defenses. Several antibiotics are no longer effective owing to the evolution of antimicrobial-resistant (AMR) bacteria, hence, the constant development of novel antibacterial agents. Naturally occurring antibacterial agents may be potential candidates for AMR bacterial infection treatments; however, caution should be taken when administering such agents due to the high incidence of toxicity. A fibrous material system from a biocompatible polymer that could be used as a skin patch for skin infections treatment caused by AMR bacteria is proposed in this study. Bee venom’s active ingredient, melittin, was fabricated using electrospinning technology. Scanning electron microscopy showed that melittin-loaded fibers had smooth surfaces with no signs of beads or pores. The average diameter of this fibrous system was measured to be 1030 ± 160 nm, indicating its successful preparation. The melittin fibers’ drug loading and entrapment efficiency (EE%) were 49 ± 3 µg/mg and 84 ± 5%, respectively. This high EE% can be another successful preparatory criterion. An in vitro release study demonstrated that 40% of melittin was released after 5 min and achieved complete release after 120 min owing to the hydrophilic nature of the PVP polymer. A concentration of ≤10 µg/mL was shown to be safe for use on human dermal fibroblasts HFF-1 after 24-h exposure, while an antibacterial MIC study found that 5 μg/mL was the effective antimicrobial concentration for S. aureus, A. baumannii, E. coli and Candida albicans yeast. A melittin-loaded fibrous system demonstrated an antibacterial zone of inhibition equivalent to the control (melittin discs), suggesting its potential use as a wound dressing patch for skin infections.

Geriatric patients are more likely to suffer from multiple chronic diseases that require using several drugs, which are commonly ingested. However, to enhance geriatric patients’ convenience, the electrospun nanofiber system was previously proven to be a successful alternative for the existing oral dosage forms, i.e., tablets and capsules. These nanofibers prepared either as single- or multi-layered fibers could hold at least one active compound in each layer. They might also be fabricated as ultra-disintegrated fibrous films for oral cavity administration, i.e., buccal or sublingual, to improve the bioavailability and intake of the administered drugs. Therefore, in this work, a combination of nifedipine and atorvastatin calcium, which are frequently prescribed for hypertension and hyperlipidemia patients, respectively, was prepared in a coaxial electrospinning system for buccal administration. Scanning electron microscopy image showed the successful preparation of smooth, non-beaded, and non-porous surfaces of the drug-loaded nanofibers with an average fiber diameter of 968 ± 198 nm. In contrast, transmission electron microscopy distinguished the inner and outer layers of those nanofibers. The disintegration of the drug-loaded nanofibers was ≤12 s, allowing the rapid release of nifedipine and atorvastatin calcium to 61% and 47%, respectively, after 10 min, while a complete drug release was achieved after 120 min. In vitro, a drug permeation study using Franz diffusion showed that the permeation of both drugs from the core–shell nanofibers was enhanced significantly (p < 0.05) compared to the drugs in a solution form. In conclusion, the development of drug-loaded nanofibers containing nifedipine and atorvastatin calcium can be a potential buccal delivery system.

Local production of pharmaceuticals plays a vital role in maintaining resilience of national healthcare systems, especially when it comes to facilitating access to needed medicines and decreasing exposure to imports and international supply chains. Pharma is a research-intensive industry and the systemic lack of governance and support to R&D activities in this sector, among other host of related issues such as unsupportive regulatory regimes and human resources capacity limitations, is one of the major impediments to the diversifying of locally produced pharmaceuticals portfolio. In this review, an overview of the current pharmaceutical production system in Saudi Arabia, its major challenges, and proposed remedies to address them will be highlighted.

Treatment of posterior eye diseases with intravitreal injections of drugs, while effective, is invasive and associated with side effects such as retinal detachment and endophthalmitis. In this work, we have formulated a model compound, rapamycin (RAP), in nanoparticle-based eye drops and evaluated the delivery of RAP to the posterior eye tissues in a healthy rabbit. We have also studied the formulation in experimental autoimmune uveitis (EAU) mouse model with retinal inflammation. Aqueous RAP eye drops were prepared using N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (Molecular Envelope Technology - MET) containing 0.23 ± 0.001% w/v RAP with viscosity, osmolarity, and pH within the ocular comfort range, and the formulation (MET-RAP) was stable in terms of drug content at both refrigeration and room temperature for one month. The MET-RAP eye drops delivered RAP to the choroid-retina with a Cmax of 145 ± 49 ng/g (tmax = 1 h). The topical application of the MET-RAP eye drops to the EAU mouse model resulted in significant disease suppression compared to controls, with activity similar to dexamethasone eye drops. The MET-RAP eye drops also resulted in a reduction of RORγt and an increase in both Foxp3 expression and IL-10 secretion, indicating a mechanism involving the inhibition of Th17 cells and the up-regulation of T-reg cells. The MET-RAP formulation delivers RAP to the posterior eye segments, and the formulation is active in EAU.

Tacrolimus (TAC) suspension is used to treat moderate to severe atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC). The objectives of this study were to formulate the hydrophobic compound TAC (TAC) in an aqueous eye drop formulation and study its ocular biodistribution on topical ocular application to a healthy rabbit model, with the overall aim of using the formulation to treat AKC and VKC. A thin-film hydration method was used to encapsulate TAC within the chitosan-based amphiphile: N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (Molecular Envelope Technology – MET) in an aqueous formulation. The formulation was characterized, and its stability studied under three storage conditions for one month. The ocular distribution of the formulation was studied in healthy rabbits and the ocular tissues and the whole blood analyzed by LC-MS/MS. A 200 nm nanoparticle formulation (MET-TAC) containing 0.1 ± 0.002% w/v TAC was produced with viscosity, osmolarity and pH within the ocular comfort range, and the formulation was stable on refrigeration for one month. On topical application, the TAC concentrations in rabbit cornea and conjunctiva one hour after dosing were 4452 ± 2289 and 516 ± 180 ng/g of tissue, respectively. A topical ocular aqueous TAC eye drop formulation has been prepared with the ability to deliver sufficient drug to the relevant ocular surface tissues.