Specific inter-molecular interaction with sodium glycocholate generates the co-amorphous system showing higher physical stability and aqueous solubility of Y5 receptor antagonist of neuropeptide Y, a brick dust molecule.

Drugs with poor water and lipid solubility are termed "brick dust." We previously successfully developed a co-amorphous system of a novel neuropeptide Y5 receptor antagonist (AntiY5R), a brick dust molecule, using sodium taurocholate (NaTC) as a co-former. However, the maximum improvement in AntiY5R dissolution by the co-amorphous system was only approximately 10 times greater than that of the crystals. Therefore, in the current study, other bile salts, including sodium cholate (NaC), sodium chenodeoxycholate (NaCC), and sodium glycocholate (NaGC), were examined as co-formers to further improve AntiY5R dissolution. NaC, NaCC, and NaGC have glass transition temperatures above 150 °C. All three co-amorphous systems prepared successfully retained the amorphous form of AntiY5R for 3 months at 40 °C, but the co-amorphous system with NaGC (AntiY5R-NaGC; 1:9 M ratio) provided the highest improvement in AntiY5R dissolution, which was approximately 50 times greater than that of the crystals. Possible intermolecular interactions via the glycine moiety of NaGC more than the other bile salts would contribute to the highest dissolution enhancement with AntiY5R-NaGC. Thus, NaGC would be a promising co-former for formulating stable co-amorphous systems to enhance the dissolution behavior of brick dust molecules.

Preparation, optimization, and characterization of genistein-ginseng long-acting polymeric gel as a breast cancer treatment alternative.

To address the prevalent genistein (GST) metabolism and inadequate intestinal absorption, an oral long-acting and gastric in-situ gelling gel was designed to encapsulate and localize the intestinal release of the loaded genistein-ginseng (GST-GNS) solid dispersion. Because of the high breast perfusion of GST upon oral absorption, the GST-GNS solid dispersion was developed to enhance GST's dissolution and penetration while offering a synergistic impact against breast cancer (BC). Physiochemical analysis of the GST-GNS solid dispersion, release analysis, gel characterizations, storage stability, penetration, and in vitro cytotoxicity studies were carried out. GST-GNS solid dispersion showed improved dissolution and penetration as compared to raw GST. GST-GNS solid dispersion homogenous shape particles and hydrophilic contacts were revealed by scanning electron microscopy and Fourier Transform-Infrared analysis, respectively. GST-GNS solid dispersion's diffractogram shows the amorphous character. A second modification involved creating a gastric in-situ gelling system loaded with GST-GNS solid dispersion. This system demonstrated improved GST penetration employing the solid dispersion, as well as the localizing of the GST release at the intestinal media and antitumor synergism against BC. For a better therapeutic approach for BC, the innovative oral GST long-acting gel encasing the GST-GNS solid dispersion would be recommended.

Generality of Enhancing the Dissolution Rates of Free Acid Amorphous Solid Dispersions by the Incorporation of Sodium Hydroxide.

The incorporation of a counterion into an amorphous solid dispersion (ASD) has been proven to be an attractive strategy to improve the drug dissolution rate. In this work, the generality of enhancing the dissolution rates of free acid ASDs by incorporating sodium hydroxide (NaOH) was studied by surface-area-normalized dissolution. A set of diverse drug molecules, two common polymer carriers (copovidone or PVPVA and hydroxypropyl methylcellulose acetate succinate or HPMCAS), and two sample preparation methods (rotary evaporation and spray drying) were investigated. When PVPVA was used as the polymer carrier for the drugs in this study, enhancements of dissolution rates from 7 to 78 times were observed by the incorporation of NaOH into the ASDs at a 1:1 molar ratio with respect to the drug. The drugs having lower amorphous solubilities showed greater enhancement ratios, providing a promising path to improve the drug release performance from their ASDs. Samples generated by rotary evaporation and spray drying demonstrated comparable dissolution rates and enhancements when NaOH was added, establishing a theoretical foundation to bridge the ASD dissolution performance for samples prepared by different solvent-removal processes. In the comparison of polymer carriers, when HPMCAS was applied in the selected system (indomethacin ASD), a dissolution rate enhancement of 2.7 times by the incorporated NaOH was observed, significantly lower than the enhancement of 53 times from the PVPVA-based ASD. This was attributed to the combination of a lower dissolution rate of HPMCAS and the competition for NaOH between IMC and HPMCAS. By studying the generality of enhancing ASD dissolution rates by the incorporation of counterions, this study provides valuable insights into further improving drug release from ASD formulations of poorly water-soluble drugs.

Liquisolid Technique: A Novel Technique with Remarkable Applications in Pharmaceutics.

Recently, it has been observed that newly developed drugs are lipophilic and have low aqueous solubility issues, which results in a lower dissolution rate and bioavailability of the drugs. To overcome these issues, the liquisolid technique, an innovative and advanced approach, comes into play. This technique involves the conversion of the drug into liquid form by dissolving it in non-volatile solvent and then converting the liquid medication into dry, free-flowing, and compressible form by the addition of carrier and coating material. It offers advantages like low cost of production, easy method of preparation, and compactable with thermo labile and hygroscopic drugs. It has been widely applied for BCS II drugs to enhance dissolution profile. Improving bioavailability, providing sustained release, minimizing pH influence on drug dissolution, and improving drug photostability are some of the other promising applications of this technology. This review article presents an overview of the liquisolid technique and its applications in formulation development.

Insights into the Mechanism of Enhanced Dissolution in Solid Crystalline Formulations.

Solid dispersions are a promising approach to enhance the dissolution of poorly water-soluble drugs. Solid crystalline formulations show a fast drug dissolution and a high thermodynamic stability. To understand the mechanisms leading to the faster dissolution of solid crystalline formulations, physical mixtures of the poorly soluble drugs celecoxib, naproxen and phenytoin were investigated in the flow through cell (apparatus 4). The effect of drug load, hydrodynamics in the flow through cell and particle size reduction in co-milled physical mixtures were studied. A carrier- and drug-enabled dissolution could be distinguished. Below a certain drug load, the limit of drug load, carrier-enabled dissolution occurred, and above this value, the drug defined the dissolution rate. For a carrier-enabled behavior, the dissolution kinetics can be divided into a first fast phase, a second slow phase and a transition phase in between. This study contributes to the understanding of the dissolution mechanism in solid crystalline formulations and is thereby valuable for the process and formulation development.

Inhalable porous particles as dual micro-nano carriers demonstrating efficient lung drug delivery for treatment of tuberculosis.

Inhalation therapy treating severe infectious disease is among the more complex and emerging topics in controlled drug release. Micron-sized carriers are needed to deposit drugs into the lower airways, while nano-sized carriers are of preference for cell targeting. Here, we present a novel and versatile strategy using micron-sized spherical particles with an excellent aerodynamic profile that dissolve in the lung fluid to ultimately generate nanoparticles enabling to enhance both extra- and intra-cellular drug delivery (i.e., dual micro-nano inhalation strategy). The spherical particles are synthesised through the condensation of nano-sized amorphous silicon dioxide resulting in high surface area, disordered mesoporous silica particles (MSPs) with monodispersed size of 2.43 µm. Clofazimine (CLZ), a drug shown to be effective against multidrug-resistant tuberculosis, was encapsulated in the MSPs obtaining a dry powder formulation with high respirable fraction (F.P.F. <5 µm of 50%) without the need of additional excipients. DSC, XRPD, and Nitrogen adsorption-desorption indicate that the drug was fully amorphous when confined in the nano-sized pores (9-10 nm) of the MSPs (shelf-life of 20 months at 4 °C). Once deposited in the lung, the CLZ-MSPs exhibited a dual action. Firstly, the nanoconfinement within the MSPs enabled a drastic dissolution enhancement of CLZ in simulated lung fluid (i.e., 16-fold higher than the free drug), increasing mycobacterial killing than CLZ alone (p = 0.0262) and reaching concentrations above the minimum bactericidal concentration (MBC) against biofilms of M. tuberculosis (i.e., targeting extracellular bacteria). The released CLZ permeated but was highly retained in a Calu-3 respiratory epithelium model, suggesting a high local drug concentration within the lung tissue minimizing risk for systemic side effects. Secondly, the micron-sized drug carriers spontaneously dissolve in simulated lung fluid into nano-sized drug carriers (shown by Nano-FTIR), delivering high CLZ cargo inside macrophages and drastically decreasing the mycobacterial burden inside macrophages (i.e., targeting intracellular bacteria). Safety studies showed neither measurable toxicity on macrophages nor Calu-3 cells, nor impaired epithelial integrity. The dissolved MSPs also did not show haemolytic effect on human erythrocytes. In a nutshell, this study presents a low-cost, stable and non-invasive dried powder formulation based on a dual micro-nano carrier to efficiently deliver drug to the lungs overcoming technological and practical challenges for global healthcare.

Formulation of Glibenclamide proniosomes for oral administration: Pharmaceutical and pharmacodynamics evaluation.

Glibenclamide (GB), oral antidiabetic sulfonylurea, is used in the management of diabetes mellitus type II. It suffers from low bioavailability due to low water solubility. This work aimed to enhance the dissolution of GB by formulating the drug as a proniosomes which then improves the pharmacological effect. GB proniosomal formulations were prepared using a slurry method with sucrose as a carrier. The formulations were characterized by particle size, zeta potential, entrapment efficiency %, flow properties of the powder, and in vitro dissolution study. The pharmacological effect was also assessed by determining and measuring the fasting blood glucose level (BGL) before and after the treatment. Formulating GB proniosomes with the slurry method produces a free-flowing powder with a particle size range from 190.050 ± 43.204 to 1369.333 ± 150.407 nm and the zeta potential was above 20 mV (-24 to -58 mV), indicating good stability. The dissolution rate for all formulations was higher than that of the pure drug, indicating the efficiency of the proniosome in enhancing the drug solubility. A significant reduction in the fasting blood glucose level (73 %) was observed in animals treated with proniosomal formulation with no sign of liver damage. In contrast, the pharmacodynamics results show a significant reduction in fasting blood glucose level for animals treated with proniosomes compared to a 17.6 % reduction in BGL after treatment with pure drug. Moreover, the histopathological results showed no sign of liver damage that occurred with proniosomal treatment. GB proniosomal formulations is a promising drug delivery system with good therapeutic efficacy and stability.

Saquinavir-Piperine Eutectic Mixture: Preparation, Characterization, and Dissolution Profile.

The dissolution rate of the anti-HIV drug saquinavir base (SQV), a poorly water-soluble and extremely low absolute bioavailability drug, was improved through a eutectic mixture formation approach. A screening based on a liquid-assisted grinding technique was performed using a 1:1 molar ratio of the drug and the coformers sodium saccharinate, theobromine, nicotinic acid, nicotinamide, vanillin, vanillic acid, and piperine (PIP), followed by differential scanning calorimetry (DSC). Given that SQV-PIP was the only resulting eutectic system from the screening, both the binary phase and the Tammann diagrams were adapted to this system using DSC data of mixtures prepared from 0.1 to 1.0 molar ratios in order to determine the exact eutectic composition. The SQV-PIP system formed a eutectic at a composition of 0.6 and 0.40, respectively. Then, a solid-state characterization through DSC, powder X-ray diffraction (PXRD), including small-angle X-ray scattering (SAXS) measurements to explore the small-angle region in detail, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and a powder dissolution test were performed. The conventional PXRD analyses suggested that the eutectic mixture did not exhibit structural changes; however, the small-angle region explored through the SAXS instrument revealed a change in the crystal structure of one of their components. FT-IR spectra showed no molecular interaction in the solid state. Finally, the dissolution profile of SQV in the eutectic mixture was different from the dissolution of pure SQV. After 45 min, approximately 55% of the drug in the eutectic mixture was dissolved, while, for pure SQV, 42% dissolved within this time. Hence, this study concludes that the dissolution rate of SQV can be effectively improved through the approach of using PIP as a coformer.

Development of Robust Tablet Formulations with Enhanced Drug Dissolution Profiles from Centrifugally-Spun Micro-Fibrous Solid Dispersions of Itraconazole, a BCS Class II Drug.

Fibre-based oral drug delivery systems are an attractive approach to addressing low drug solubility, although clear strategies for incorporating such systems into viable dosage forms have not yet been demonstrated. The present study extends our previous work on drug-loaded sucrose microfibres produced by centrifugal melt spinning to examine systems with high drug loading and investigates their incorporation into realistic tablet formulations. Itraconazole, a model BCS Class II hydrophobic drug, was incorporated into sucrose microfibres at 10, 20, 30, and 50% w/w. Microfibres were exposed to high relative humidity conditions (25 °C/75% RH) for 30 days to deliberately induce sucrose recrystallisation and collapse of the fibrous structure into powdery particles. The collapsed particles were successfully processed into pharmaceutically acceptable tablets using a dry mixing and direct compression approach. The dissolution advantage of the fresh microfibres was maintained and even enhanced after humidity treatment for drug loadings up to 30% w/w and, importantly, retained after compression into tablets. Variations in excipient content and compression force allowed manipulation of the disintegration rate and drug content of the tablets. This then permitted control of the rate of supersaturation generation, allowing the optimisation of the formulation in terms of its dissolution profile. In conclusion, the microfibre-tablet approach has been shown to be a viable method for formulating poorly soluble BCS Class II drugs with improved dissolution performance.

Microwave Synthesis of Nanostructured Functionalized Polylactic Acid (nfPLA) for Incorporation Into a Drug Crystals to Enhance Their Dissolution.

Active pharmaceutical ingredients that have low aqueous solubility pose a challenge in the field of drug delivery. In this paper we report for the first time the synthesis of nano-structured, hydrophilized polylactic acid (nfPLA) and its application in the delivery of low solubility drugs. Microwave induced acid oxidation was used to generate nfPLA where the oxygen concentration increased from 27.0 percent to 41.0 percent. Also, the original non dispersible PLA was converted to a relatively dispersible form with an average particle size of 131.4 nm and a zeta potential of -23.3 mV. Small quantities of the nfPLA were incorporated into the crystals (0.5 to 2.0 % by weight) of a highly hydrophobic, low solubility antifungal drug Griseofulvin (GF) to form a composite (GF-nfPLA). An antisolvent approach was used for the synthesis of the drug composite. SEM and Raman imaging showed non-uniform distribution of the nfPLA on the crystal surface. The solubility of GF increased from 8.89 µg/mL to as high as 49.67 µg/mL for the GF-nfPLA. At the same time zeta potential changed from -15.4 mV to -39.0 mV, therefore the latter was a relatively stable colloid. Octanol-water partitioning also showed a similar effect as logP reduced from 2.16 for pure GF to 0.55 for GF-nfPLA. In vitro dissolution testing showed six times higher aqueous solubility of GF-nfPLA compared to pure GF. The time for 50 (T50) and 80 % (T80) dissolution reduced significantly for the nfPLA composites; T50 reduced from 40.0 to 14.0 min and T80 reduced form unachievable to 47.0 min. Overall, the PLA which is an FDA approved, bioabsorbable polymer can be used to enhance the dissolution of hydrophobic pharmaceuticals and this can lead to higher efficacy and lower the required dosage for drugs.

Development and in-vitro evaluation of chitosan and glyceryl monostearate based matrix lipid polymer hybrid nanoparticles (LPHNPs) for oral delivery of itraconazole.

Itraconazole (ICZ) is a broad spectrum antifungal drug, but used as second or third line therapy due to its low and erratic oral bioavailability. This work was carried out to prepare and characterize matrix type lipid-polymer hybrid nanoparticles (LPHNPs) for dissolution enhancement of ICZ. LPHNPs were prepared using solvent diffusion/emulsification technique. Matrix LPHNPs were composed of chitosan (polymer), glyceryl monostearate (lipid) and poloxamer 188 (stabilizer). LPHNPs loaded with ICZ (LPHNPs-1, LPHNPs-2, LPHNPs-3 and LPHNPs-4) were developed using varying concentration of chitosan whereas LPHNPs (LPHNPs-5, LPHNPs-6, LPHNPs-7 and LPHNPs-8) were prepared using varying concentrations of poloxamer 188. LPHNPs loaded with ICZ were further evaluated for entrapment efficiency, particle size, polydispersity index (PDI), zeta potential and dissolution profiles at biorelevant pH conditions. The particle size (LPHNPs-1 to LPHNPs-4) was found to be in range of 421-588 nm with PDI values 0.34-0.41. The particles size of LPHNPs-5 to LPHNPs-8 was found to be in range of 489-725 nm with PDI 0.34-0.74. The entrapment efficiency of LPHNPs-1 to LPHNPs-4 was found to be in range of 85.21%-91.34%. The entrapment efficiency of LPHNPs-5 to LPHNPs-8 was found to be in range 78.32%-90.44%. . The scanning electron microscopy of optimized formulations LPHNPs-1 and LPHNPs-5 indicated formation of oval shaped nanoparticles. DSC thermogram of ICZ loaded LPHNPs also depicted the conversion of crystalline form of ICZ into amorphous form demonstrating the internalization and dissolution enhancement of drug in the hybrid matrix. The cumulative drug dissolved at acidic pH 1.2 was found to be 23.3% and 19.8% for LPHNPs-1 and LPHNPs-5 respectively. Similarly at basic pH values 7.4, cumulative amount of drug dissolved was 90.2% and 83.4% for LPHNPs-1 and LPHNPs-5 respectively. Drug dissolution kinetics exhibited fickian diffusion best described by Korse-meyer Peppas model. The results suggested that chitosan and glyceryl monostearate based matrix LPHNPs could be used as promising approach for dissolution enhancement of ICZ which could further increase its bioavailability.

Preparation and Evaluation of Directly Compressible Orally Disintegrating Tablets of Cannabidiol Formulated Using Liquisolid Technique.

This study demonstrated the implementation of a liquisolid technique to formulate directly compressible orally disintegrating tablets (ODTs). Cannabidiol (CBD), a hydrophobic cannabinoid, was prepared as a liquisolid powder using microcrystalline cellulose-colloidal silicon dioxide as a carrier-coating material. Different liquid vehicles differing in their volatility, hydrophilicity, and viscosity were investigated. Each of the CBD-ODTs comprised CBD liquisolid powder (10 mg CBD), superdisintegrant, flavors, lubricant, and filler. The physical mixture (PM) ODT was prepared as a control. Ethanol-based ODTs (CBD-EtOH-ODTs) had comparable tablet properties and stability to CBD-PM-ODTs. ODTs with nonvolatile-vehicle-based liquisolid powder had lower friability but longer disintegration times as compared with CBD-PM-ODTs and CBD-EtOH-ODTs. Compression pressure influenced the thickness, hardness, friability, and disintegration of the ODTs. With a suitable compression pressure to yield 31-N-hardness-ODTs and superdisintegrant (4-8%), CBD-ODTs passed the friability test and promptly disintegrated (≤25 s). Times to dissolve 50% of CBD-PM-ODTs, CBD-EtOH-ODTs, and nonvolatile-vehicle-based CBD-ODTs were 10.1 ± 0.7, 3.8 ± 0.2, and 4.2 ± 0.4-5.0 ± 0.1 min, respectively. CBD-EtOH-ODTs exhibited the highest dissolution efficiency of 93.5 ± 2.6%. Long-term and accelerated storage indicated excellent stability in terms of tablet properties and dissolution. Nonvolatile-vehicle-based CBD-ODTs exhibited a higher percentage of remaining CBD. This study provides useful basic information for the development of ODT formulations using a liquisolid technique application.

Rivaroxaban lyospheres prepared by a dimethyl sulfoxide-based spray-freeze-drying process.

Spray-freeze-drying (SFD) processes are usually using aqueous solvent systems, which however, exclude the use of SFD for poorly water-soluble drugs/excipients. Here, we evaluated dimethyl sulfoxide for its suitability in formulating SFD particles (lyospheres®). Rivaroxaban was spray-freeze-dried from DMSO solutions containing polyvinyl pyrrolidone (PVP; Kollidon® 25), vinylpyrrolidone-vinyl acetate copolymer (PVP-VA; Kollidon® VA64) or polyvinyl alcohol 4-88 (PVA) forming porous lyospheres® (median particle size 250 to 350 µm). Rivaroxaban was amorphous with all three polymers, which in combination with the high porosity resulted in rapid dissolution in vitro within 10 min. Consequently, this translated in lower Tmax (0.5-1.0 h) after oral administration of lyospheres® to rats (compared with Tmax of 4 h with coarse rivaroxaban). Lyosphere formulations achieved a distinct bioavailability increase (AUC(0-inf) = 1487 ± 657 ng*h/ml with PVP; 4426 ± 1553 ng*h/ml with PVP-VA; 9569 ± 3868 ng*h/ml with PVA lyospheres®; whereas 385 ± 145 ng*h/ml with coarse rivaroxaban). These in vitro and in vivo results underlined the benefit of using DMSO in SFD that can broaden the applicability of the SFD process to a much larger repertoire of poorly water-soluble drugs/excipients.

Smart Oral pH-Responsive Dual Layer Nano-Hydrogel for Dissolution Enhancement and Targeted Delivery of Naringenin Using Protein-Polysaccharides Complexation Against Colorectal Cancer.

Naringenin (NAR) is a natural anticancer, but it has not been developed for clinical use despite its therapeutic potential due to its low water solubility, low membrane permeability, first-pass metabolism, and low bioavailability. To overcome these problems, the optimization and preparation of NAR-Soy protein complex (NAR-Sp) led to the optimum ratio of their interaction using Fourier Transform-Infrared spectroscopy (FT-IR) as the first level and layer of the formulation. The second layer of the formulation was to incorporate the NAR-Sp complex in aqueous-based gel-forming. The most optimum nanosuspension was determined using the gel sedimentation, sustained-release, pH-selective and targeted system. The most optimum components combinations and complex were characterized using different characterization tools, such as, the particle size analysis, SEM, TEM, PXRD and FT-IR. In addition, the optimum nanosuspension was characterized for its nanoparticle sensitivity against colorectal cancer cells using MTT assay in comparison to the untreated, naringenin, and blank groups. The complex enhanced the NAR's dissolution. The complex incorporation in the optimum nano-encapsulating system was characterized by the sustained-release and pH-selective behaviors to target the NAR release at the site of action or absorption. Interestingly, the optimum nano-encapsulating system was showing better colorectal cytotoxicity results in comparison to the other groups.

Formulation Development of Mirtazapine Liquisolid Compacts: Optimization Using Central Composite Design.

Mirtazapine is a tetracyclic anti-depressant with poor water solubility. The aim of this study was to improve the dissolution rate of mirtazapine by delivering the drug as a liquisolid compact. Central composite design (CCD) was employed for the preparation of mirtazapine liquisolid compacts. In this, the impacts of two independent factors, i.e., excipient ratio (carrier:coating) and different drug concentration on the response of liquisolid system were optimized. Liquisolid compacts were prepared using propylene glycol as a solvent, microcrystalline cellulose as a carrier, and silicon dioxide (Aerosil) as the coating material. The crystallinity of the formulated drug and the interactions between the excipients were examined using X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR), respectively. The dissolution study for the liquisolid compact was carried out as per FDA guidelines. The results showed loss of crystallinity of the mirtazapine in the formulation and was completely solubilized in non-volatile solvent and equally dispersed throughout the powder system. Moreover, drug dissolution was found to be higher in liquisolid compacts than the direct compressed conventional tablets (of mirtazapine). The liquisolid technique appears to be a promising approach for improving the dissolution of poorly soluble drugs like mirtazapine.

Determination of Alteration in Micromeritic Properties of a Solid Dispersion: Brunauer-Emmett-Teller Based Adsorption and Other Structured Approaches.

The present study is focused on the use of solid dispersion technology to triumph over the solubility-related problems of bexarotene which is currently used for treating various types of cancer and has shown potential inhibitory action on COVID-19 main protease and human ACE2 receptors. It is based on comparison of green locust bean gum and synthetic poloxamer as polymers using extensive mechanistic methods to explore the mechanism behind solubility enhancement and to find suitable concentration of drug to polymer ratio to prepare porous 3rd generation solid dispersion. The prepared solid dispersions were characterized using different studies like X-ray diffraction (XRD), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), differential scanning calorimetry (DSC), and particle size analysis in order to determine the exact changes occurred in the product which are responsible for enhancing solubility profiles of an insoluble drug. The results showed different profiles for particle size, solubility, dissolution rate, porosity, BET, and Langmuir specific surface area of prepared solid dispersions by using different polymers. In addition to the comparison of polymers, the BET analysis deeply explored the changes occurred in all dispersions when the concentration of polymer was increased. The optimized solid dispersion prepared with MLBG using lyophilization technique showed reduced particle size of 745.7±4.4 nm, utmost solubility of 63.97%, pore size of 211.597 Å, BET and Langmuir specific surface area of 5.6413 m2/g and 8.2757 m2/g, respectively.

Drug-loaded mesoporous silica on carboxymethyl cellulose hydrogel: Development of innovative 3D printed hydrophilic films.

3D printing has been explored as an emerging technology for the development of versatile and printable materials for drug delivery. However, the alliance of 3D printing and nanomaterials has, to date, been little explored in pharmaceutics. Herein, a mesoporous silica with nanostructured pores, SBA-15, was used as a drug carrier for triamcinolone acetonide, a hydrophobic drug, with the aim of incorporating the drug formulation in a hydrophilic printable ink. The adsorption of the drug in the SBA-15 pores was confirmed by the decrease in its surface area and pore volume, along with an increase in the apparent aqueous solubility of triamcinolone acetonide, as shown by in vitro release studies. Thereafter, a hydrophilic ink composed of carboxymethyl cellulose containing drug-loaded SBA-15 was formulated and 3D printed as hydrophilic polymeric film using the semisolid extrusion technique (SSE). The 3D printed films showed complete drug release after 12 h, and the presence of the triamcinolone acetonide-loaded SBA-15 improved their in vitro mucoadhesion, suggesting their promising application in oral mucosa treatments. Besides representing an innovative platform to develop water-based mucoadhesive formulations containing a hydrophobic drug, this is the first report proposing the development of SSE 3D printed nanomedicines containing drug-loaded mesoporous silica.

Application of a liquisolid technique to cannabis sativa extract compacts: Effect of liquid vehicles on the dissolution enhancement and stability of cannabinoids.

This work describes the application of liquisolid technique to enhance cannabinoid dissolution from Cannabis sativa L. (CS) compacts. Effects of five vehicles, namely, volatile (ethanol) and nonvolatile (caprylocaproyl macrogolglycerides, polyethylene glycol 400, oleoyl macrogolglycerides and polysorbate 20) liquids, on tablet properties, dissolution and stability were investigated. The viscid oleoresin CS extract was mixed with vehicles before being transformed into free-flowing powder by the use of microcrystalline cellulose and colloidal silica as carrier and coating materials. Liquid vehicles had a nonsignificant effect on liquid load factor of CS extract. CS liquisolid compacts had acceptable tableting properties in terms of weight variation, friability, hardness, content uniformity and disintegration time. Different vehicles affected the hardness, disintegration, and wettability of CS compacts and thus the dissolution behaviors of cannabinoids to different extents. Dissolutions of cannabinoids from CS compacts were rate-limited by the disintegration process. Liquisolid formulations using nonvolatile liquids with low polarity or high hydrophilic-lipophilic balance yielded more than 90% cannabinoid dissolution. Stability studies revealed nonsignificant changes in tablet characteristics, cannabinoid content and dissolutions of CS compacts when stored at 5 ± 3 °C for 3 months. This work presents a general concept of how to successfully formulate CS extract with cannabinoid dissolution enhancement characteristics.

Effects of Formulation and Manufacturing Process on Drug Release from Solid Self-emulsifying Drug Delivery Systems Prepared by High Shear Mixing.

This study sought to investigate the influence of formulation and process factors of the high shear mixing (HSM) on the properties of solid self-emulsifying drug delivery systems (S-SEDDS) containing the model drug carvedilol (CAR). Firstly, liquid SEDDS (L-SEDDS) were prepared by mixing castor oil with different proportions of surfactant (Solutol or Kolliphor RH40) and cosolvent (Transcutol or PEG400). A miscible L-SEDDS with high drug solubility (124.3 mg/g) was selected and gave rise to 10% (m/m) CAR loaded-emulsion with reduced particle size. Then, a factorial experimental design involving five component's concentration and two process factors was used to study the solidification of the selected L-SEDDS by HSM. CAR content, diffractometric profile, and in vitro dissolution were determined. Morphological and flow analyses were also performed. Porous and spherical particles with mean sizes ranging from 160 to 210 µm were obtained. Particle size was not affected by any formulation factor studied. Powder flowability, in turn, was influenced by L-SEDDS and crospovidone concentration. CAR in vitro dissolution from S-SEDDS was significantly increased compared to the drug as supplied and was equal (pH 1.2) or lower (pH 6.8) than that determined for L-SEDDS. Colloidal silicon dioxide decreased drug dissolution, whereas an increase in water-soluble diluent lactose and L-SEDDS concentration increased CAR dissolution. The proper selection of liquid and solid constituents proved to be crucial to developing an S-SEDDS by HSM. Indeed, the results obtained here using experimental design contribute to the production of S-SEDDS using an industrially viable process.

Solid self emulsifying drug delivery system: Superior mode for oral delivery of hydrophobic cargos.

A significant proportion of recently approved drug molecules possess poor aqueous solubility which further restrains their desired bioavailability. Poor aqueous solubility of these drugs poses significant hurdles in development of novel drug delivery systems and achieving target response. Self-emulsifying drug delivery systems (SEDDS) emerged as an insightful approach for delivering highly hydrophobic entities to enhance their bioavailability. Conventional SEDDS were developed in a liquid form which owned numerous shortcomings like low stability and drug loading efficiency, fewer choices of dosage forms and irreversible precipitation of drug or excipients. To address these curbs solid-SEDDS (S-SEDDS) was introduced as an efficient strategy that combined advantages of solid dosage forms such as increased stability, portability and patient compliance along with substantial improvement in the bioavailability. S-SEDDS are isotropic mixtures of oil, surfactant, solvent and co-solvents generated by solidification of liquid or semisolid self-emulsifying ingredients onto powders. The present review highlights components of S-SEDDS, their peculiarities to be considered while designing solid dosage forms and various methods of fabrication. Lastly, key challenges faced during development, applications and future directions for the research in this area are thoroughly summarized.