In Vitro Evaluation of a Solid Supersaturated Self Nanoemulsifying Drug Delivery System (Super-SNEDDS) of Aprepitant for Enhanced Solubility

Aprepitant (APR) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its low aqueous solubility. The objective of the current work is to develop self-nanoemulsifying drug delivery systems (SNEDDS) of APR to enhance its aqueous solubility. Preformulation studies involving screening of excipients for solubility and emulsification efficiency were carried out. Pseudo ternary phase diagrams were constructed with blends of oil (Imwitor® 988), cosolvent (Transcutol® P), and various surfactants (Kolliphor® RH40, Kolliphor® ELP, Kolliphor® HS15). The prepared SNEDDS were characterized for droplet size and nanoemulsion stability after dilution. Supersaturated SNEDDS (super-SNEDDS) were prepared to increase the quantity of loaded APR into the formulations. HPMC, PVP, PVP/VA, and Soluplus® were used as polymeric precipitation inhibitors (PPI). PPIs were added to the formulations at 5% and 10% by weight. The influence of the PPIs on drug precipitation was investigated. In vitro lipolysis test was carried out to simulate digestion of formulations in the gastrointestinal tract. Optimized super-SNEDDS were formulated into free-flowing granules by adsorption on the porous carriers such as Neusilin® US2. In vitro dissolution studies of solid super-SNEDDS formulation revealed an increased dissolution rate of the drug due to enhanced solubility. Consequently, a formulation to improve the solubility and potentially bioavailability of the drug was developed.

Carrier Effect in Development of Rifampin Loaded Proliposome for Pulmonary Delivery: A Quality by Design Study

Purpose: Pulmonary Tuberculosis (TB) is a worldwide life-threatening infection. The recommended anti-TB regimen contains oral administration of classical first-line drugs such as rifampin for 6-24 months which often leads to low patient compliance due to high adverse effects; therefore, lung localized pulmonary delivery of anti-TB agents may be a suitable alternative. Proliposomes free-flowing powders are well-known carriers for lung delivery since they can form liposomes by hydration. Liposomes are safe and useful carriers for lung delivery due to their phospholipid structure. Methods: Porous lactose and mannitol as proliposome carriers were prepared by spray drying technique using sucrose and citric acid as templating agents. Design expert® software was used to develop forty formulations due to the porous and non-porous carriers, which were characterized with respect to their weight yield, density, and flowability. Rifampin-loaded hydrated liposomes were produced and evaluated for size, morphology, loading capacity and encapsulation efficiency. The optimized proliposomes in vitro release and aerosolization properties were evaluated. Solid-state analysis was confirmed by Differential Scanning Calorimetry (DSC). Results: Porous lactose surface area was 80 folds higher than non-porous one, respectively. Optimized porous-based proliposome indicated the acceptable aerosolization properties, including mass median aerodynamic diameter (MMAD) of 6.21±0.36 µm and fine particle fraction (FPF) of 9.17±0.18% with a fast rifampin release (80%) within one hour. DSC results proved that there was no change in the solid-state of rifampin during the production process. Conclusion: Hence, it seems; rifampin loaded inhalable proliposomes may be a suitable system for delivering liposomal rifampin into the lungs.

Amine-Grafted Mesoporous Carbons as Benzocaine-Delivery Platforms

Smart porous carriers with defined structure and physicochemical properties are required for releasing the therapeutic drug with precise control of delivery time and location in the body. Due to their non-toxicity, ordered structure, and chemical and thermal stability, mesoporous carbons can be considered modern carriers for active pharmaceutical ingredients whose effectiveness needs frequent dosing algorithms. Here, the novel benzocaine delivery systems based on ordered mesoporous carbons of the cubic structure were obtained with the use of a hard template method and functionalization with amine groups at 40 °C for 8 h. It has been shown that amine grafting strongly modifies the surface chemistry and textural parameters of carbons. All samples indicated good sorption ability towards benzocaine, with evident improvement following the functionalization with the amine groups. The sorption capacity and drug release kinetics were strongly affected by the porosity of carbon carriers and the surface functional groups. The smallest amount of benzocaine (~12%) was released from pristine mesoporous carbon, which could be correlated with strong API–carrier interactions. Faster and more efficient release of the drug was observed in the case of triethylenetetramine modified carbon (~62%). All benzocaine delivery platforms based on amine-grafted mesoporous carbons revealed high permeability through the artificial membrane.

Encapsulation of lipid-based formulations in porous carriers for controlled drug delivery

: Lipid-based formulations have recently been investigated as a promising approach to enhance the bioavailability of drugs, especially poorly water-soluble drugs. The encapsulation of lipid-based formulations in porous materials can result in a transformation of liquids or semisolid forms to solid dosage forms. Moreover, the specific structure of porous carriers could offer an enhanced ability to load and control active pharmaceutical ingredients. Although there have been prominent reports on lipid-based formulations and porous materials as promising technologies for controlled drug release, the overall methods of encapsulating lipid-based formulations need to be discussed for further formulation investigations. This review aims to present the key strategies used for producing porous carriers containing lipid-based formulations. We also discuss methods that enhance the encapsulation efficiency of loaded drugs within porous structures (instead of lipid-based formulations). Moreover, the critical factors that affect tablet formation are outlined. This overview of lipid-based formulations encapsulated within porous materials provides a summary of the technical methods used in the development of these formulations and their clinical translation.

Stress-Dependent Particle Interactions of Magnesium Aluminometasilicates as Their Performance Factor in Powder Flow and Compaction Applications

In the pharmaceutical industry, silicates are commonly used excipients with different application possibilities. They are especially utilized as glidants in low concentrations, but they can be used in high concentrations as porous carriers and coating materials in oral solid drug delivery systems. The desirable formulations of such systems must exhibit good powder flow but also good compactibility, which brings opposing requirements on inter-particle interactions. Since magnesium aluminometasilicates (MAS) are known for their interesting flow behavior reported as “negative cohesivity” yet they can be used as binders for tablet compression, the objective of this experimental study was to investigate their particle interactions within a broad range of mechanical stress from several kPa to hundreds of MPa. Magnesium aluminometasilicate (Neusilin® US2 and Neusilin® S2)-microcrystalline cellulose (Avicel® PH102) physical powder mixtures with varying silicate concentrations were prepared and examined during their exposure to different pressures using powder rheology and compaction analysis. The results revealed that MAS particles retain their repulsive character and small contact surface area under normal conditions. If threshold pressure is applied, the destruction of MAS particles and formation of new surfaces leading to particle interactions are observed. The ability of MAS particles to form interactions intensifies with increasing pressure and their amount in a mixture. This “function switching” makes MAS suitable for use as multifunctional excipients since they can act as a glidant or a binder depending on the applied pressure.

Development of non-soil media capable of degrading organic nitrogen to nitrate, as in natural soil

Artificial soil materials are unable to catalyse nitrification because added organic substances suppress nitrifying bacteria. We used a multiple parallel mineralization method, which enables the use of organic fertilizers in hydroponics, to support nitrification in non-soil materials. In this method, microorganisms immobilized on porous carriers produce inorganic nitrate from organic substances, as in natural soil. The carriers also released phosphate and potassium ions. Microorganisms produced nitrate from organic substances when immobilized on polyurethane resin, rockwool, vermiculite, oyster shell lime, and rice husk charcoal. The optimal amount of organic material added daily to 100 mL of carrier held 6 mg of organic N. Vegetable plants grew on inoculated materials but not on uninoculated materials. These results show that non-soil materials can be used to create artificial soils in which plants can be grown with the addition of organic fertilizer, as in natural soil.

Lawsone Derived Zn (II) and Fe (III) Metal Organic Frameworks with pH Dependent Emission for Controlled Drug Delivery

Fluorescent biocompatible porous carriers have been investigated as suitable probes for drug delivery and sensing applications owing to their intrinsic fluorescence and high surface area originating from their porous structure...

Influence of Carrier Structure and Physicochemical Factors on Immobilisation of Fungal Laccase in Terms of Bisphenol A Removal

Laccase from Pleurotus ostreatus was immobilised on porous Purolite® carriers and amino-functionalised ultrafiltration membranes. The results indicated a correlation between the carrier structure and the activity of laccase immobilised thereon. The highest activity was obtained for carriers characterised by a small particle size and a larger pore diameter (the porous carriers with an additional spacer (C2 and C6) and octadecyl methacrylate beads with immobilised laccase activity of 5.34 U/g, 2.12 U/g and 7.43 U/g, respectively. The conditions of immobilisation and storage of immobilised laccase were modified to improve laccase activity in terms of bisphenol A transformation. The highest laccase immobilisation activity was obtained on small bead carriers with a large diameter of pores incubated in 0.1 M phosphate buffer pH 7 and for immobilisation time of 3 h at 22 °C. The immobilised LAC was stable for four weeks maintaining 80–90% of its initial activity in the case of the best C2, C6, and C18 carriers. The immobilised laccase transformed 10 mg/L of BPA in 45% efficiency and decreased its toxicity 3-fold in the Microtox tests. The effectiveness of BPA transformation, and the legitimacy of conducting this process due to the reduction of the toxicity of the resulting reaction products have been demonstrated. Reusability of immobilised LAC has been proven during BPA removal in 10 subsequent batches.