Hydrophilic Ready-to-use Vehicles and Compounded Topical Medications.

Pharmaceutical compounding has a crucial role for the health of patients, allowing the preparation of formulation out of market or for a personalized therapy. This study is aimed to conduct a screening of possible ready-to-use hydrophilic vehicles for the preparation of topical dosage forms. Incorporation tests of several active pharmaceutical ingredients were performed, and the physical stability of the extemporaneous formulations was assessed by performing an accelerated centrifuge test. The results showed that it was possible to realize several physically stable topical medications without using special equipment or instruments, guaranteeing a fast and repeatable preparation process. The goal of this work is to provide compounding pharmacists a table that summarizes some of the possible vehicles that can be used for the formulation of topical treatments.

Lipophilic Ready-to-use Vehicles and Compounded Topical Medications.

The preparation of formulations that are not currently on the market or prepared for customized therapy is possible by pharmaceutical compounding. In this study, incorporation tests of some active pharmaceutical ingredients in five ready-touse lipophilic semisolid vehicles were performed, and the physical stability of the prepared extemporaneous formulations was assessed by performing an accelerated centrifuge test. The results demonstrated that it was possible to formulate physically stable topical medications without using special equipment or instruments, ensuring a fast, efficient, and repeatable preparation process. The objective of this work was to provide to compounding pharmacists a table that summarizes some of the semisolid lipophilic vehicles, such as creams water/oil, and ointments, that can be used for the formulation of topical treatments.

Extemporaneous Topical Minoxidil Solutions for the Treatment of Androgenetic Alopecia- Stability Studies and Incorporation Tests of Active Pharmaceutical Ingredients in Aloplus Total Base.

Minoxidil is one of the most employed active pharmaceutical ingredients for the  treatment of androgenetic alopecia. The authors propose a new method for production of minoxidil lotions using Aloplus Total. The latter is a propylene glycol-free liquid base in which the presence of hydroxypropyl-ß-cyclodextrin and ethanol allows the solubilization of high drug amounts. Minoxidil intrinsic solubility in the base was determined, and a comprehensive chemical and physical stability study was conducted on 8% w/w minoxidil lotions. Incorporation tests of different active pharmaceutical ingredients that can be combined to 5% w/w minoxidil were also carried out. The analyses showed that minoxidil intrinsic solubility in the new base was 85.93 mg/mL ± 4.17 mg/mL (8.64% w/w ± 0.42% w/w) at 25°C, and the topical lotions were found to be physically and chemically stable for more than 180 days when stored at 25°C or 40°C. Incorporation tests of several active pharmaceutical ingredients also were successful, indicating that Aloplus Total is a liquid vehicle also useful for the preparation of minoxidil-based topical lotions for a synergistic treatment of androgenetic alopecia.

Celecoxib-hydroxypropyl-ß-cyclodextrin inclusion complex in a chitosan/PEO-PPO-PEO block copolymer matrix: Structural effect and drug release.

HYPOTHESIS: Triblock copolymers of poly(ethylene oxide) and poly(propylene oxide)-based matrices, such as Poloxamer 407 (P407) or Pluronic® F127, are extensively utilized in drug delivery and permeation systems due to their FDA approval and listing in the US and European Pharmacopoeias. The study hypothesizes that incorporating 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and the celecoxib-HP-ß-CD inclusion complex into a 16 wt% P407 and chitosan blend in an aqueous acetic acid solution will affect the system's rheological and structural properties. EXPERIMENTS: Rheological, small-angle X-ray scattering (SAXS), and dynamic light scattering (DLS) experiments were conducted to assess the impact of acetic acid and chitosan on the 16 wt% P407 and chitosan blend. Additionally, in vitro drug release studies were performed to monitor the drug release profile over time. FINDINGS: The addition of HP-ß-CD was found to inhibit gel formation in the 16 wt% P407 and chitosan blend. However, the presence of the celecoxib-HP-ß-CD inclusion complex showed no significant structural effects compared to P407 blended with chitosan alone. Rheological and SAXS analyses demonstrated that acetic acid led to the formation of a lamellar phase due to the lower pH, facilitating injectability. The presence of chitosan in acetic acid resulted in the detection of a hexagonal phase, affecting the release of celecoxib.

Investigating the prilling/vibration technique to produce gastric-directed drug delivery systems for misoprostol.

Prilling/vibration technique to produce oral microcapsules was explored to achieve local delivery of misoprostol (MIS), a prostaglandin E1 analogue indicated for the treatment of gastric-duodenal ulcers, at the gastric mucosa. To improve MIS chemical stability and reduce its associated systemic side effects, drug delivery systems were designed and developed as microcapsules consisting of a core of sunflower oil and MIS (Fs6 and Fs14) or a MIS complex with hydroxypropyl-beta-cyclodextrin (HP-ß-CD) (Fs18), confirmed by specific studies, and a polymeric shell. The produced microcapsules showed high encapsulation efficiencies for those with MIS solubilized in sunflower oil (>59.86 %) and for the microcapsules with MIS/HP-ß-CD (97.61 %). To demonstrate the ability of these systems to deliver MIS into the stomach, swelling and drug release experiments were also conducted in simulated gastric fluid. Among the three formulations, FS18 showed gastric release within 30 min and was the most advantageous formulation because the presence of the MIS/HP-ß-CD inclusion complex ensured a greater ability to stabilise MIS in the simulated gastric environment. In addition, these new systems have a small size (<540 µm), and good flow properties and the dose of the drug could be easily adapted using different amounts of microcapsules (flexibility), making them a passepartout for different age population groups.

Extemporaneous Topical Minoxidil Solutions for the Treatment of Alopecia: Stability Studies and Incorporation Tests of Active Ingredients in ALOPLUS FAST Base.

Minoxidil is a vasodilator drug generally employed for the treatment of various forms of alopecia. In this article, the authors propose an alternative to the formulation reported in the British Pharmacopoeia for the realization of topical minoxidil -based solutions using ALOPLUS FAST. This liquid vehicle is an ethanol- and propylene glycol-free base which allows the complete solubilization of minoxidil, thanks to the presence of hydroxypropyl-ß-cyclodextrin. Solubility and chemical stability studies of the active ingredient in the formulation at a concentration of 5% w/w and physical stability studies of this extemporaneous preparation are reported. Incorporation tests of various active pharmaceutical ingredients that can be combined with minoxidil for alopecia synergic treatment have been carried out. Analyses were performed by using a high-pressure liquid chromatography analytical method. The results showed that the intrinsic solubility of the drug in the liquid base was 62.37 mg/mL ± 0.85 mg/mL (5.24 w/w ± 0.07% w/w) at 25°C; minoxidil was chemically stable in ALOPLUS FAST; and the formulation was physically stable for more than six months, under different storage conditions. Incorporation tests of several active pharmaceutical ingredients in 2% to 4% w/w minoxidil formulations were successful as well.

Physicochemical Stability of the Extemporaneous Ibuprofen Oral Suspension in "Wagner" Base.

This article discusses a new method for the preparation of extemporaneous ibuprofen-based suspensions for use in paediatric patients. This method allows the preparation of extemporaneous suspensions up to concentrations of 200 mg/5 mL by using a liquid base named "Wagner." A comprehensive physicochemical stability study was conducted on the formulation at a drug concentration of 200 mg/5 mL by performing high-pressure liquid chromatography and Turbiscan analyses. Chromatographic analyses of the samples demonstrated the chemical stability of the active pharmaceutical ingredient in the base for more than 90 days when the formulations were stored at 4°C and 25°C. Visual and optical analyses evidenced a reversible, slightly creaming phenomenon when the formulations were stored at 4°C or 25°C restoring the initial suspension by simply shaking.

Telemedicine in Cancer Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Telemedicine is defined as the delivery of medical services through a variety of telecommunication tools. This novel approach can fit the needs of cancer patients who cannot often reach clinics due to their disabling symptoms. In this population of patients, pain is undoubtedly the most important symptom which dramatically affects the quality of life. Our work aimed to investigate the effectiveness of telemedicine in the management of cancer pain in order to assess the feasibility of a combination between telemedicine and traditional in-person visits; we also propose a model of integration of these two approaches. METHODS: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework to conduct our study. Quality assessment and risk of bias were performed according Cochrane criteria. Results were reported as mean differences and summarized using forest plots. We performed a trial sequential analysis (TSA) to assess the conclusiveness of our results. RESULTS: Pain severity score and pain interference were lower for patients treated with telemedicine compared to those undergoing classical management (mean difference: -0.408; P =< .001 and -0.492; P = .004, respectively). TSA confirmed that our results were statistically significant and pointed out the need of other studies to reach the required sample size. PROSPERO registration: CRD42022333260. CONCLUSIONS: Telemedicine can be effectively used to manage cancer pain. This novel approach will certainly have a revolutionary economic and organizational impact on health care systems in the next future. Furthermore, the model herein proposed could help set up an algorithm to safely and efficiently implement telemedicine.

Phytophthora × cambivora as a Major Factor Inciting the Decline of European Beech in a Stand within the Southernmost Limit of Its Natural Range in Europe.

The objective of this study was to investigate the role of the oomycete Phytophthora× cambivora in the decline affecting European beech (Fagus sylvatica) in the Nebrodi Regional Park (Sicily, southern Italy). In a survey of a beech forest stand in the heart of the park, Phytophthora× cambivora was the sole Phytophthora species recovered from the rhizosphere soil and fine roots of trees. Both A1 and A2 mating type isolates were found. Direct isolation from the stem bark of trees showing severe decline symptoms and bleeding stem cankers yielded exclusively P. gonapodyides, usually considered as an opportunistic pathogen. The mean inoculum density of P.× cambivora in the rhizosphere soil, as determined using the soil dilution plating method and expressed in terms of colony forming units (cfus) per gm of soil, the isolation frequency using leaf baiting, and the percentage of infected fibrous roots from 20 randomly selected beech trees with severe decline symptoms (50 to 100 foliage transparency classes) were 31.7 cfus, 80%, and 48.6%, respectively. These were significantly higher than the corresponding mean values of 20 asymptomatic or slightly declining trees, suggesting P.× cambivora is a major factor responsible for the decline in the surveyed stand.

The other side of the crisis: organizational flexibility in balancing Covid-19 and non-Covid-19 health-care services.

BACKGROUND: Many healthcare systems have been unable to deal with Covid-19 without influencing non-Covid-19 patients with pre-existing conditions, risking a paralysis in the medium term. This study explores the effects of organizational flexibility on hospital efficiency in terms of the capacity to deliver healthcare services for both Covid-19 and non-Covid-19 patients. METHOD: Focusing on Italian health system, a two-step strategy is adopted. First, Data Envelope Analysis is used to assess the capacity of hospitals to address the needs of Covid-19 and non-Covid-19 patients relying on internal resource flexibility. Second, two panel regressions are performed to assess external organizational flexibility, with the involvement in demand management of external operators in the health-care service, examining the impact on efficiency in hospital capacity management. RESULTS: The overall response of the hospitals in the study was not fully effective in balancing the needs of the two categories of patients (the efficiency score is 0.87 and 0.58, respectively, for Covid-19 and non-Covid-19 patients), though responses improved over time. Furthermore, among the measures providing complementary services in the community, home hospitalization and territorial medicine were found to be positively associated with hospital efficiency (0.1290, p < 0.05 and 0.2985, p < 0.01, respectively, for non-Covid-19 and Covid-19 patients; 0.0026, p < 0.05 and 0.0069, p < 0.01, respectively, for non-Covid-19 and Covid-19). In contrast, hospital networks are negatively related to efficiency in Covid-19 patients (-0.1037, p < 0.05), while the relationship is not significant in non-Covid-19 patients. CONCLUSIONS: Managing the needs of Covid-19 patients while also caring for other patients requires a response from the entire healthcare system. Our findings could have two important implications for effectively managing health-care demand during and after the Covid-19 pandemic. First, as a result of a naturally progressive learning process, the resource balance between Covid-19 and non-Covid-19 patients improves over time. Second, it appears that demand management to control the flow of patients necessitates targeted interventions that combine agile structures with decentralization. Finally, untested integration models risk slowing down the response, giving rise to significant costs without producing effective results.

Chitosan/sulfobutylether-ß-cyclodextrin based nanoparticles coated with thiolated hyaluronic acid for indomethacin ophthalmic delivery.

Indomethacin (IND) is topically administered for the treatment of the anterior segment diseases such as conjunctivitis, uveitis, and inflammation prevention for post-cataract surgery, as well as posterior segment diseases as macular edema. Currently IND is available as 0.1% w/v hydroxypropyl-ß-cyclodextrin-based eye drop formulation and its bioavailability is limited by several drawbacks such as the nasolacrimal duct draining, the reflex blinking and the low volume of the conjunctival sac. In this study, chitosan (CS)/sulfobutylether-ß-cyclodextrin (SBE-ß-CD) based nanoparticles (NPs) with a mean diameter of 340 (±7) nm, a ζ-potential value of +18.3 (±0.5) mV and coated with thiolated low molecular weight hyaluronic acid were formulated to improve both the solubility and the residential time in the conjunctival sac of the loaded drug IND. The NPs were prepared through the ionotropic gelation technique, exploiting the interaction between the positively charged amino group of CS and the negatively charged sulfonic group of SBE-ß-CD. The mucoadhesive properties of the NPs were evaluated on chicken trachea and esophagus tissues using a texture analyser. The irritability effects of NPs were disclaimed with Hecam test. The developed coated NPs showed increased residential time in the conjunctival sac, displayed no irritancy or toxicity for local administration, making them an optimal and innovative drug delivery system for the treatment of anterior segment inflammation diseases. On the other hand, the uncoated NPs displayed better permeating properties since they are smaller and could be further exploited for the treatment of posterior segment diseases.

Implementations and strategies of telehealth during COVID-19 outbreak: a systematic review.

BACKGROUND: Telehealth is an effective option to fight the outbreak of COVID-19. This review aims to systematically characterize the utilization and applications of telehealth during the COVID-19 pandemic focusing mainly on technology implementations. METHODS: This study was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The literature search was conducted in Science Direct, IEEE XPLORE, Scopus, and Web of Science databases from January 2020 until July 2021, with an English language restriction. A quality assessment was based on the Critical Appraisal Skills Programs checklist. RESULTS: The included studies focused on the implementation of technology for telehealth, multidisciplinary approach, service satisfaction, guidelines, and medical training. They provided illustrative insight into the strategy of telehealth in different medical specialties, such as pediatric gastroenterology, oncology, ophthalmology, and laryngology. Nonsurgical specialties had the greatest number of telehealth visits. Clinicians showed positive attitudes toward the implementation of video telehealth visits; patients report high levels of satisfaction with this care and strong interest in continuing this modality as a significant portion of clinical practice. CONCLUSIONS: This systematic review provided an illustrative insight into the strategy of telehealth for different purposes. According to our findings, telehealth may be used in different medical area with a clear strategy of intervention according to patients' and doctors' needs.

Direct cyclodextrin-based powder extrusion 3D printing for one-step production of the BCS class II model drug niclosamide.

Niclosamide (NCS) is a drug that has been used as an anthelmintic and anti-parasitic drug for about 40 years. Recently, some studies have highlighted its potential in treating various tumors, allowing a repositioning of this drug. Despite its potential, NCS is a Biopharmaceutical Classification System (BCS) Class II drug and is consequently characterized by low aqueous solubility, poor dissolution rate and reduced bioavailability, which limits its applicability. In this work, we utilize a very novel technique, direct powder extrusion (DPE) 3D printing, which overcomes the limitations of previously used techniques (fused deposition modelling, FDM) to achieve direct extrusion of powder mixtures consisting of NCS, hydroxypropyl methylcellulose (HPMC, Affinisol 15 LV), hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and polyethylene glycol (PEG) 6000. For the first time, direct printing of powder blends containing HP-ß-CD was conducted. For all tablets, in vitro dissolution studies showed sustained drug release over 48 h, but for tablets containing HP-ß-CD, the release was faster. Solid-state characterization studies showed that during extrusion, the drug lost its crystal structure and was evenly distributed within the polymer matrix. All printed tablets have exhibited good mechanical and physical features and a stability of the drug content for up to 3 months. This innovative printing technique has demonstrated the possibility to produce personalized pharmaceutical forms directly from powders, avoiding the use of filament used by FDM.

Magnetic implants in vivo guiding sorafenib liver delivery by superparamagnetic solid lipid nanoparticles.

HYPOTHESIS: Solid lipid nanoparticles (SLNs), co-encapsulating superparamagnetic iron oxide nanoparticles and sorafenib, have been exploited for magnetic-guided drug delivery to the liver. Two different magnetic configurations, both comprising two small magnets, were under-skin implanted to investigate the effect of the magnetic field topology on the magnetic SLNP accumulation in liver tissues. A preliminary simulation analysis was performed to predict the magnetic field topography for each tested configuration. EXPERIMENTS: SLNs were prepared using a hot homogenization approach and characterized using complementary techniques. Their in vitro biological behavior was assessed in HepG-2 liver cancer cells; wild-type mice were used for the in vivo study. The magnet configuration that resulted in a higher magnetic targeting efficiency was investigated by evaluating the iron content in homogenated murine liver tissues. FINDINGS: SLNs, characterized by an average size smaller than 200 nm, retained their superparamagnetic behavior and relevant molecular resonance imaging properties as negative contrast agents. The evaluation of iron accumulation in the liver tissues was consistent with the magnetic induction profile of each magnet configuration, concurring with the results predicted by simulation analysis and obtained by measurements in living mice.

Radiosynthesis and characterization of [18F]BS224: a next-generation TSPO PET ligand insensitive to the rs6971 polymorphism.

PURPOSE: Translocator protein 18-kDa (TSPO) positron emission tomography (PET) is a valuable tool to detect neuroinflammed areas in a broad spectrum of neurodegenerative diseases. However, the clinical application of second-generation TSPO ligands as biomarkers is limited because of the presence of human rs6971 polymorphism that affects their binding. Here, we describe the ability of a new TSPO ligand, [18F]BS224, to identify abnormal TSPO expression in neuroinflammation independent of the rs6971 polymorphism. METHODS: An in vitro competitive inhibition assay of BS224 was conducted with [3H]PK 11195 using membrane proteins isolated from 293FT cells expressing TSPO-wild type (WT) or TSPO-mutant A147T (Mut), corresponding to a high-affinity binder (HAB) and low-affinity binder (LAB), respectively. Molecular docking was performed to investigate the interaction of BS224 with the binding sites of rat TSPO-WT and TSPO-Mut. We synthesized a new 18F-labeled imidazopyridine acetamide ([18F]BS224) using boronic acid pinacol ester 6 or iodotoluene tosylate precursor 7, respectively, via aromatic 18F-fluorination. Dynamic PET scanning was performed up to 90 min after the injection of [18F]BS224 to healthy mice, and PET imaging data were obtained to estimate its absorbed doses in organs. To evaluate in vivo TSPO-specific uptake of [18F]BS224, lipopolysaccharide (LPS)-induced inflammatory and ischemic stroke rat models were used. RESULTS: BS224 exhibited a high affinity (Ki = 0.51 nM) and selectivity for TSPO. The ratio of IC50 values of BS224 for LAB to that for HAB indicated that the TSPO binding affinity of BS224 has low binding sensitivity to the rs6971 polymorphism and it was comparable to that of PK 11195, which is not sensitive to the polymorphism. Docking simulations showed that the binding mode of BS224 is not affected by the A147T mutation and consequently supported the observed in vitro selectivity of [18F]BS224 regardless of polymorphisms. With optimal radiochemical yield (39 ± 6.8%, decay-corrected) and purity (> 99%), [18F]BS224 provided a clear visible image of the inflammatory lesion with a high signal-to-background ratio in both animal models (BPND = 1.43 ± 0.17 and 1.57 ± 0.37 in the LPS-induced inflammatory and ischemic stroke rat models, respectively) without skull uptake. CONCLUSION: Our results suggest that [18F]BS224 may be a promising TSPO ligand to gauge neuroinflammatory disease-related areas in a broad range of patients irrespective of the common rs6971 polymorphism.

Microfluidic preparation and in vitro evaluation of iRGD-functionalized solid lipid nanoparticles for targeted delivery of paclitaxel to tumor cells.

Solid lipid nanoparticles (SLNs) can combine the advantages of different colloidal carriers and prevent some of their disadvantages. The production of nanoparticles by means of microfluidics represents a successful platform for industrial scale-up of nanoparticle manufacture in a reproducible way. The realisation of a microfluidic technique to obtain SLNs in a continuous and reproducible manner encouraged us to create surface functionalised SLNs for targeted drug release using the same procedure. A tumor homing peptide, iRGD, owning a cryptic C-end Rule (CendR) motif is responsible for neuropilin-1 (NRP-1) binding and for triggering extravasation and tumor penetration of the peptide. In this study, the Paclitaxel loaded-SLNs produced by microfluidics were functionalized with the iRGD peptide. The SLNs proved to be stable in aqueous medium andwere characterized by a Z-average under 150 nm, a polydispersity index below 0.2, a zeta-potential between -20 and -35 mV and a drug encapsulation efficiency around 40%. Moreover, in vitro cytotoxic effects and cellular uptake have been assessed using 2D and 3D tumour models of U87 glioblastoma cell lines. Overall, these results demonstrate that the surface functionalization of SLNs with iRGD allow better cellular uptake and cytotoxicity ability.

Stability of Diazepam Enema Extemporaneous Formulation in Manzoni Base.

The authors provide a report on the preparation of an extemporaneous liquid formulation of diazepam enema using an alcohol-free base solution for use by both pediatric and adult patients. A solubility study using this base and the chemical stability of the drug in this formulation was performed by using a high-pressure liquid chromatography analytical method. Results of this study showed that the intrinsic solubility of the drug in this liquid base was 6.03 mg/mL ± 0.06 mg/mL and that diazepam was chemically stable when the formulation was stored at 25°C over a period of 3 months.

Development of purified glycogen derivatives as siRNA nanovectors.

Purified Glycogen (PG) is a highly hyper branched carbohydrate, characterized by high water solubility and very moderate increase in viscosity. The dendrimeric structure of PG, appropriately functionalized, makes it an alternative to current synthetic gene delivery agents. The present study explores the preparation of purified glycogen polycationic derivatives (PGPDs), developed and characterized starting from a single step reaction between PG and N,N-dialkylamino alkyl halides. Subsequently PGPDs were used for the complexation of a model siRNA nucleic acid, a transfection reagent siRNA and a fluorescein-labelled dsRNA oligomer. PGPDs-siRNA complexes were fully characterized by agarose gel electrophoresis and their efficacy was assessed by both confocal microscopy and transfection assays on breast and renal cancer cells. Results proved that PGPDs-siRNA complexes were efficient and not cytotoxic, maintaining their spherical and dendrimeric structure and, particularly, were able to effectively transfect the target cells by releasing the siRNA.

Spray-dried mucoadhesive microparticles based on S-protected thiolated hydroxypropyl-ß-cyclodextrin for budesonide nasal delivery.

Budesonide (BUD) is used as first choice therapy for the treatment of allergic rhinitis, a chronic allergic-immune condition with an increased incidence in the pediatric population. The main problem of BUD nasal formulations is related to its poor aqueous solubility (S0 = 5.03·10-5 M), sometimes compensated by the administration of high doses of the drug. The ability of thiolated hydroxypropyl-ß-cyclodextrin (HP- ß -CD-SH, 100 mM) to increase the water solubility of BUD (SHP- ß-CD-SH = 10.9·10-3 M) more than pristine hydroxypropyl- ß -cyclodextrin (HP- ß-CD, SHP- ß-CD = 4.3·10-3 M) has been previously demonstrated. Considering that S-protected thiomers have the advantage of increasing the stability of thiols over a wide pH range prolonging their residence time at the target site, 2-mercapto-nicotinic acid (MNA) was used in this study to protect the free thiol groups on HP- ß -CD-SH generating the corresponding S-protected cyclodextrin (HP-ß-CD-MNA). Besides, given the increased stability and processability of HP-ß-CD-MNA, mucoadhesive microparticles (MPs) were prepared via spray-drying of aqueous solutions of the inclusion complex HP-ß-CD-MNA/BUD. MPs were morphologically and dimensionally homogeneous exhibiting an average diameter of 3.24 ± 0.57 µm. Over time these MPs formed larger aggregates with an average diameter of 10-50 µm, suitable for the design of intranasal delivery systems. Differential scanning calorimetry analyses revealed the absence of crystalline BUD from spray-dried complexes. Dissolution studies shown that spray-dried MPs dissolved quickly and the complexed drug was completely solubilized within the first 20 min of the dissolution process. Cell viability assay indicated that spray-dried complexes are safe. In vitro mucoadhesion studies on freshly excised porcine nasal mucosa showed a 1.4- and 2.3-fold prolonged mucosal residence time of HP- ß -CD-SH/BUD and HP-ß-CD-MNA/BUD in comparison to the unmodified cyclodextrin (CD), respectively. Rheological behaviour of spray-dried MPs complexes/mucus mixtures confirmed the results of the mucoadhesion studies, as the dynamic viscosity of the spray-dried inclusion complexes HP-ß-CD-SH/BUD and HP-ß-CD-MNA/BUD was 1.1-fold and 2.4 fold increased in comparison to the unmodified HP-ß-CD/BUD complex. According to these results, MPs comprising HP- ß -CD-MNA/BUD might be a promising tool for nasal delivery of poorly water-soluble corticosteroids such as BUD.

From oil to microparticulate by prilling technique: Production of polynucleate alginate beads loading Serenoa Repens oil as intestinal delivery systems.

Natural oils that are rich in biologically active polyunsaturated fatty acids have many health benefits but have insufficient bioavailability and may oxidize in the gastrointestinal tract. For these reasons and to improve the handling as well, the possibility of incorporating a natural oil, extracted from Serenoa Repens fruits (SR-oil), in alginate-based beads was investigated. SR-oil has been used from centuries in both traditional and modern medicine for various nutraceutical or therapeutic purposes such as, in both sexes, as a general tonic, for genitourinary problems, to increase sexual vigor, as a diuretic or to treat in male lower urinary tract symptoms and benign prostatic hyperplasia. In this study, alginate-based beads prepared by vibration technology, also known as prilling technique, were explored as SR-oil delivery systems. Twenty-seven different formulations (F1-F27) were produced starting from stable emulsions for the period of the production. The formulations having spheroid shape (sfericity factor <0.07), high formulation yield (>90%) and high encapsulation efficiency (EE% > 80) were selected for further characterizations. Gas chromatographic analysis revealed a high loading of lauric acid as principal component of SR-oil allowing to calculate the content of total fatty acids (>50%) into the beads. Swelling behavior and release features were also studied at different pH values. The swelling of the beads and their SR-oil release were negligible for the first 2 h in simulated gastric fluid (pH 1.2), and appreciable in simulated intestinal fluid (pH 6.8). The release data were fitted by various equations to define the release kinetic mechanism. In addition, the selected formulation (F16) was stable to the oxidation not only during the formulation process, but also after 3 months of storage at room temperature. In summary, these polynucleate alginate beads, produced by prilling technique, are promising systems for improving the intestinal specific delivery and bioavailability of health-promoting bioactive SR-oil.