24 Factorial Design Formulation Optimization and In vitro Characterization of Desloratadine Nanosuspension Prepared Using Antisolvent Precipitation.

INTRODUCTION: Desloratadine, a second-generation antihistaminic drug, is poorly watersoluble and requires amelioration of the dissolution rate to improve its pharmacokinetics properties. METHOD: This study investigated the impact of polymer, surfactant types, and concentration on the particle size, zeta potential, and dissolution efficiency of nanosuspensions formulated through the solvent antisolvent precipitation method. To optimize the delivery of Desloratadine nanosuspension, we used Minitab software and a 4-factor, 2-level full factorial design. Physicochemical properties and drug release studies were conducted to evaluate the suggested nanosuspension formulations. The optimization goals included minimizing particle size and zeta potential while maximizing dissolution efficiencies. RESULT: The selected optimal nanosuspension demonstrated favourable values, including a particle size of 478.63 ± 15.67 nm, a zeta potential of -36.24 ± 3.21 mV, and dissolution efficiencies in double distilled water and buffer of 90.29 ± 3.75 % and 93.70 ± 3.67 %, respectively. The optimized formulation was subjected to additional analysis using X-ray powder diffraction (XPRD), scanning and transmission electron microscopy (SEM and TEM), and Fourier-transform infrared spectroscopy (FTIR). CONCLUSION: The optimized nanosuspension formulation also underwent further studies under optimal lyophilization conditions, revealing the effectiveness of mannitol as a cryoprotectant at a concentration of 8%.

Insulin therapy in type 2 diabetes: Insights into clinical efficacy, patient-reported outcomes, and adherence challenges.

Insulin therapy plays a crucial role in the management of type 2 diabetes as the disease progresses. Over the past century, insulin formulations have undergone significant modifications and bioengineering, resulting in a diverse range of available insulin products. These products show distinct pharmacokinetic and pharmacodynamic profiles. Consequently, various insulin regimens have em-erged for the management of type 2 diabetes, including premixed formulations and combinations of basal and bolus insulins. The utilization of different insulin regimens yields disparate clinical outcomes, adverse events, and, notably, patient-reported outcomes (PROs). PROs provide valuable insights from the patient's perspective, serving as a valuable mine of information for enhancing healthcare and informing clinical decisions. Adherence to insulin therapy, a critical patient-reported outcome, significantly affects clinical outcomes and is influenced by multiple factors. This review provides insights into the clinical effectiveness of various insulin preparations, PROs, and factors impacting insulin therapy adherence, with the aim of enhancing healthcare practices and informing clinical decisions for individuals with type 2 diabetes.

Oral bioavailability enhancement of doxazosin mesylate: Nanosuspension versus self-nanoemulsifying drug delivery systems.

Background and purpose: Doxazosin mesylate (DOX) is an antihypertensive drug that possesses poor water solubility and, hence, poor release properties. Both nanosuspensions and self-nanoemulsifying drug delivery systems (SNEDDS) are becoming nanotechnology techniques for the enhancement of water solubility of different drugs. Experimental approach: The study's goal was to identify the best drug delivery system able to enhance the release and antihypertensive effect of DOX by comparing the physical characteristics such as particle size, zeta potential, entrapment efficiency, release rate, and main arterial blood pressure of DOX-loaded nanosuspensions and SNEDDS in liquid and solid form. Key results: DOX nanosuspension preparation had a particle size of 385±13 nm, poly-dispersity index of 0.049±3, zeta potential of 50 ± 4 mV and drug release after 20 min (91±0.43 %). Liquid SNEDDS had a droplet size of 224±15 nm, poly-dispersity index of (0.470±0.01), zeta potential of -5±0.10 mV and DR20min of 93±4 %. Solid SEDDS showed particle size of 79±14 nm, poly-dispersity index of 1±0.00, a zeta potential of -18 ±0.26 mv and DR20min of 100 ±2.72 %. Conclusion: Finally, in terms of the mean arterial blood pressure lowering, solid SNEDDS performed better effect than both liquid SNEDDS and nanosuspension (P >0.05).

Formulation and in vitro characterization of nanoemulsions containing remdesivir or licorice extract: A potential subcutaneous injection for coronavirus treatment.

The management of coronavirus necessitates that medicines are available, reasonably priced, and easy to administer. The work aimed at formulating and characterizing remdesivir and licorice extract nanoemulsions and comparing their efficacy against coronavirus for further subcutaneous injection. First, the solubility of remdesivir was determined in different oils, surfactants, and co-surfactants to choose the optimal nanoemulsion components. Nanoemulsions were optimized concerning surfactant: co-surfactant ratio (5:1, 4:1, 3:1, 2:1, and 1:1) and oil to surfactant: co-surfactant ratio (1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, and 1:1). The formulations were evaluated concerning % transmittance, emulsification time, pH, viscosity, droplet size, polydispersity index, zeta potential, drug content, transmission electron microscopy, in-vitro drug release, stability (of the optimal formulas), and antiviral effect against coronavirus. The optimal nanoemulsion formula was F7, exhibiting an acceptable pH level, a rapid emulsification rate, a viscosity of 20 cP, and 100% drug content. The formulation droplet size was 16 and 17 nm, the polydispersity index was 0.18 and 0.26, and the zeta potential was - 6.29 and - 10.34 mV for licorice extract and remdesivir nanoemulsions, respectively. However, licorice extract nanoemulsion exhibited better release and physical stability. Licorice extract nanoemulsion may be a potential subcutaneous injection for combating mild to moderate coronavirus.

Nanosuspension: A Formulation Technology for Tackling the Poor Aqueous Solubility and Bioavailability of Poorly Soluble Drugs.

The poor water solubility of numerous novel drug candidates presents significant challenges, particularly in terms of oral administration. This limitation can result in various undesirable clinical implications, such as inter-patient variability, poor bioavailability, difficulties in achieving a safe therapeutic index, increased costs, and potential risks of toxicity or inefficacy. Biopharmaceutics Classification System (BCS) class II drugs face particular hurdles due to their limited solubility in the aqueous media of the gastrointestinal tract. In such cases, parenteral administration is often employed as an alternative strategy. To address these challenges, nanosuspension techniques offer a promising solution for enhancing drug solubility and overcoming oral delivery obstacles. This technique has the potential to bridge the gap between drug discovery and preclinical use by resolving problematic solubility. This literature review has delved into contemporary nanosuspension preparation technologies and the incorporation of stabilizing ingredients within the formulation. Furthermore, the manuscript explores nanosuspension strategies for both oral and parenteral/other delivery routes, and separate discussions have been presented to establish a suitable flow that addresses the challenges and strategies relevant to each administration method.

COVID­19 pandemic fatigue among well­educated Egyptian population: cross­sectional study

Aim: The study explores the emergence of COVID 19 pandemic fatigue among well educated Egyptians measured in terms of their level of adherence toward COVID 19 protective measures along 20 months since the beginning of the pandemic. Setting and Design: A cross sectional study was conducted in October 2021, using an online questionnaire for well educated Egyptians in different governorates. Results: A total of 888 participants completed the questionnaire, their mean age was 39 ± 7.2 years and 60% of them were females. There was a strong association between the presence of either behavioral risk factors or chronic conditions and % of infection. The main sources of COVID 19 information were social media, followed by the Egyptian Ministry of health and population and WHO websites. A pandemic fatigue was observed after nearly 7 to 10 months from the pandemic emergence. The participant's age, previous COVID 19 infection, and occupation status were significant predictors for adherence to COVID 19 protective measures. The participants claimed that difficulty in remaining at home, feeling uncomfortable with face masks, the high cost of protective supplies, absence of governmental enforcement, and forgetfulness are the most perceptive barriers hindering their adherence to COVID 19 protective measures. They suggested some strategies for better adherence and reduced pandemic fatigue that includes: the implementation of governmental enforcement measures, including penalties for nonwearing masks, educational health programs, and availability of free protective supplies at the workplace. Conclusions: Pandemic fatigue was observed after 7 to 10 months from the pandemic emergence even though the high education level of the participants

COVID-19 pandemic fatigue among well-educated egyptian population: Cross-sectional study.

Aim: The study explores the emergence of COVID-19 pandemic fatigue among well-educated Egyptians measured in terms of their level of adherence toward COVID-19 protective measures along 20 months since the beginning of the pandemic. Setting and Design: A cross-sectional study was conducted in October 2021, using an online questionnaire for well-educated Egyptians in different governorates. Results: A total of 888 participants completed the questionnaire, their mean age was 39 ± 7.2 years and 60% of them were females. There was a strong association between the presence of either behavioral risk factors or chronic conditions and % of infection. The main sources of COVID-19 information were social media, followed by the Egyptian Ministry of health and population and WHO websites. A pandemic fatigue was observed after nearly 7 to 10 months from the pandemic emergence. The participant's age, previous COVID-19 infection, and occupation status were significant predictors for adherence to COVID-19 protective measures. The participants claimed that difficulty in remaining at home, feeling uncomfortable with face masks, the high cost of protective supplies, absence of governmental enforcement, and forgetfulness are the most perceptive barriers hindering their adherence to COVID-19 protective measures. They suggested some strategies for better adherence and reduced pandemic fatigue that includes: the implementation of governmental enforcement measures, including penalties for nonwearing masks, educational health programs, and availability of free protective supplies at the workplace. Conclusions: Pandemic fatigue was observed after 7 to 10 months from the pandemic emergence even though the high education level of the participants.

Résumé Objectif: L'étude explore l'émergence de la fatigue liée à la pandémie de COVID-19 chez les Égyptiens bien éduqués, mesurée en termes de niveau de respect des mesures de protection contre la COVID-19 pendant 20 mois depuis le début de la pandémie. Cadre et conception: Une coupe transversal étude a été menée en octobre 2021, à l'aide d'un questionnaire en ligne destiné aux Égyptiens bien éduqués dans différents gouvernorats. Résultats: Un total des 888 participants ont rempli le questionnaire, leur âge moyen était de 39 ± 7,2 ans et 60 % d'entre eux étaient des femmes. Il y avait une forte association entre la présence de facteurs de risque comportementaux ou de maladies chroniques et le % d'infection. Les principales sources de COVID-19 les informations étaient les médias sociaux, suivis des sites Web du ministère égyptien de la santé et de la population et de l'OMS. Une fatigue pandémique a été observée près de 7 à 10 mois après l'émergence de la pandémie. L'âge du participant, sa précédente infection à la COVID-19 et son statut professionnel étaient des prédicteurs significatifs du respect des mesures de protection contre la COVID-19. Les participants ont affirmé que la difficulté à rester à la maison, se sentir mal à l'aise avec les masques faciaux, le coût élevé des fournitures de protection, l'absence d'application gouvernementale et l'oubli sont les barrières les plus perceptibles entravant leur adhésion aux mesures de protection contre la COVID-19. Ils ont suggéré quelques stratégies pour une meilleure adhesion et réduction de la fatigue pandémique qui comprend : la mise en œuvre de mesures d'application gouvernementales, y compris des sanctions pour non-port masques, programmes de santé éducatifs et disponibilité de fournitures de protection gratuites sur le lieu de travail. Conclusions: Une fatigue pandémique a été observée 7 à 10 mois après l'émergence de la pandémie même si le haut niveau d'éducation des participants. Mots-clés: COVID-19, Égyptiens, fatigue pandémique.

Intranasal delivery of Clozapine using nanoemulsion-based in-situ gels: An approach for bioavailability enhancement.

Limited solubility and hepatic first-pass metabolism are the main causes of low bioavailability of anti-schizophrenic drug, Clozapine (CZP). The objective of the study was to develop and validate nanoemulsion (NE) based in-situ gel of CZP for intranasal administration as an approach for bioavailability enhancement. Solubility of CZP was initially investigated in different oils, surfactants and co-surfactants, then pseudoternary phase diagrams were constructed to select the optimized ratio of oil, surfactant and co-surfactant. Clear and transparent NE formulations were characterized in terms of droplet size, viscosity, solubilization capacity, transmission electron microscopy, in-vitro drug release and compatibility studies. Selected NEs were incorporated into different in-situ gel bases using combination of two thermosensitive polymers; Pluronic® F-127 (PF127) and F-68 (PF68). NE-based gels (NG) were investigated for gelation temperature, viscosity, gel strength, spreadability and stability. Moreover, selected NGs were evaluated for ex-vivo permeation, mucoadhesive strength and nasal ciliotoxicity. Peppermint oil, tween 80 and transcutol P were chosen for NE preparation owing to their maximum CZP solubilization. Clear NE points extrapolated from tween 80:transcutol P (1:1) phase diagram and passed dispersibility and stability tests, demonstrated globule size of 67.99 to 354.96 nm and zeta potential of -12.4 to -3.11 mV with enhanced in-vitro CZP release (>90% in some formulations). After incorporation of the selected N3 and N9 formulations of oil:Smix of 1:7 and 2:7, respectively to a mixture of PF127 and PF68 (20:2% w/w), the resultant NG formulations exhibited optimum gelation temperature and viscosity with enhanced CZP permeation and retention through sheep nasal mucosa. Ciliotoxicity examinations of the optimum NGs displayed no inflammation or damage of the lining epithelium and the underlying cells of the nasal mucosa. In conclusion, NE-based gels may be a promising dosage form of CZP for schizophrenia treatment.

Self-assembled biodegradable polymeric micelles to improve dapoxetine delivery across the blood-brain barrier.

BACKGROUND: Dapoxetine (DPX) is the drug of choice for the specific treatment of premature ejaculation. DPX is characterized by relatively low bioavailability (42%) and short half-life (1.5 h). The aim of this study was to improve DPX bioavailability and delivery across the blood-brain barrier (BBB) using a nanostructured DPX formulation for improved DPX efficacy and patient satisfaction. MATERIALS AND METHODS: DPX-loaded polymeric micelles (PMs) formulations (F1-F3) were characterized for particle sizes, entrapment efficiencies, and Fourier transform infrared spectroscopic and transmission electron microscopic evaluations. In addition, diffusion profiles of the prepared formulations were investigated. Animal model pharmacokinetic parameters in plasma and brain tissues were investigated and compared with commercial DPX tablets. RESULTS: Particle size analysis revealed that formulations of DPX PMs showed a narrow range of 62.7±9.3-45.45±9.1 nm for F1-F3. In addition, DPX PMs showed a sustained release pattern with 91.27%±7.64%, 79.43%±7.81%, and 63.78%±5.05% of DPX content permeated after 24 h for F1, F2, and F3, respectively. Plasma pharmacokinetic parameters for DPX PMs showed significant increase (P<0.05) for the area under drug concentration-time curves in plasma and brain tissues compared with commercial DPX tablets. CONCLUSION: DPX formulations in the form of PMs improved bioavailability and efficacy across the BBB. This DPX formulation provided improved brain delivery in order to enhance the convenience and compliance of patients.

Propolis emulgel: a natural remedy for burn and wound.

OBJECTIVES: To develop an alternative medicine, propolis, in emulgel formulation for burn and wound treatment. METHODS: The effect of two independent variables: emulsifying agent concentration and oil concentration on the cumulative amount of propolis release (dependent variable) from liquid paraffin and isopropyl palmitate emulgels was investigated. Eight formulations were prepared and evaluated for physical appearance, pH, propolis content, viscosity, and in vitro propolis release. The release results were fitted into different kinetic equations and analyzed using contour plot, interaction surface plot and one-way ANOVA. The selected emulgel formulation was investigated for its wound and burn healing activity in rats. RESULTS: All the prepared emulgels showed acceptable physical properties concerning color, homogeneity, consistency, and pH value. The concentration of emulsifying agent had more pronounced effect on propolis release than oil concentration. Formulations F1-F6 showed "anomalous" drug release, while Formulations F7 and F8 showed zero-order kinetic. CONCLUSION: The formulation F7 with 5% isopropyl palmitate, 5% emulsifier mixture, 1% hydroxyl propyl methyl cellulose, 1% oleic acid, and 10% propylene glycol is a promising formula for better management of wound and burn.

Rapid disintegrating tablets of simvastatin dispersions in polyoxyethylene-polypropylene block copolymer for maximized disintegration and dissolution.

The objective of this research was to improve the dissolution of simvastatin and to incorporate it in rapid disintegrating tablets (RDTs) with an optimized disintegration and dissolution characteristics. Polyoxyethylene-polypropylene block copolymer (poloxamer 188) was employed as a hydrophilic carrier to prepare simvastatin solid dispersions (SDs). Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray diffractometry were employed to understand the interaction between the drug and the carrier in the solid state. The results obtained from Fourier transform infrared spectroscopy showed absence of any chemical interaction between the drug and poloxamer. The results of differential scanning calorimetry and X-ray diffractometry confirmed the conversion of simvastatin to distorted crystalline state. The SD of 1:2 w/w drug to carrier ratio showed the highest dissolution; hence, it was incorporated in RDT formulations using a 32 full factorial design and response surface methodology. The initial assessments of RDTs demonstrated an acceptable flow, hardness, and friability to indicate good mechanical strength. The interaction and Pareto charts indicated that percentage of croscarmellose sodium incorporated was the most important factor affecting the disintegration time and dissolution parameter followed by the hardness value and their interaction effect. Compression force showed a superior influence to increase RDT's porosity and to fasten disintegration rather than swelling action by croscarmellose sodium. On the other hand, croscarmellose sodium was most important for the initial simvastatin release. The results suggest the potential use of poloxamer 188-based SD in RDT for the oral delivery of poor water-soluble antihyperlipidemic drug, simvastatin.

Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol.

Resveratrol is a nonflavonoid polyphenolic compound which has a broad range of desirable biological actions which include antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and antitumor activities. However, there is concern that the bioavailability of resveratrol may limit some of its clinical utility. So, the aim of this study was to enhance the dissolution rate and oral hypoglycemic and hypolipidemic effect of resveratrol. This was achieved using self-emulsifying drug delivery system. The solubility of resveratrol was determined in various oils, surfactants, and cosurfactants. Phase diagram was plotted to identify the efficient self-emulsification regions using olive oil, Tween 80, and propylene glycol. The prepared self-emulsifying drug delivery system formulations were tested for thermodynamic stability, emulsification efficiency, droplet size, zeta potential, and in vitro drug release. Self-emulsification time averaged 17-99 seconds without precipitation and the mean droplet sizes ranged from 285 to 823 nm with overall zeta potential of -2.24 to -15.4 mv. All formulations improved drug dissolution in relation to unprocessed drug with a trend of decreased dissolution parameters with increasing oil content. The optimized formula, F19, with dissolution efficiency of 94% compared to only 42% of pure drug was used to study the in vivo hypoglycemic and hypolipidemic effects of resveratrol in diabetic-induced albino rats and comparing these effects with that of pure resveratrol in different doses. Treatment with the optimized formula, F19, at 10 mg/kg had significant hypoglycemic and hypolipidemic effects in diabetic-induced albino rats which were nearly similar to the high dose (20 mg/kg) of unprocessed resveratrol. From the study, it was concluded that formulation F19 has good emulsification property with uniform globule size, satisfactory in vitro drug release profile, and significant in vivo hypoglycemic effects which identify future opportunities for resveratrol delivery.

Propolis organogel as a novel topical delivery system for treating wounds.

CONTEXT: Propolis has traditionally been used in curing infections and healing wounds and burns. OBJECTIVE: The aim of this study is to formulate pluronic lecithin organogel of propolis to improve its availability and antimicrobial activity. MATERIALS AND METHODS: Different organogels were prepared by using soybean lecithin, isopropyl palmitate, pluronic F127 and water. The effect of quantity of lecithin and pluronic F127 and percentage of oil phase was investigated. The organogels were evaluated for appearance, texture, pH, drug content and viscosity. In vitro release studies were carried out using cellophane membrane. Drug permeation through abdominal rat skin from organogels that showed high % drug release was compared to that from propolis suspension in distilled water. Finally, the antimicrobial activity of the selected propolis formulation against different bacterial isolates was compared with that of propolis suspension in water. RESULTS AND DISCUSSION: Results showed that all organogel formulations except the formula containing 10% pluronic F127, showed acceptable physical properties. Drug content of organogel formulations was in the range of 97.5-100.2%. The pH of the formulations was in the range of 5.5-6.3 that suits the skin pH, indicating skin compatibility. The viscosity was in the range of 5366-8984 cp. A significant decrease in drug release from formulations was observed with increase in concentration of lecithin and pluronic F127. Decreasing oil phase percentage to 20% w/w led to a decrease in drug release from the formulation. CONCLUSION: The formula containing 3% lecithin and 20% pluronic F127 exhibited superior skin permeation and antimicrobial activity over propolis suspension in water.

Preparation and characterization of domperidone solid dispersions.

Domperidone is a highly water insoluble drug exhibiting poor dissolution pattern. The purpose of this work was to increase the dissolution rate of Domperidone by formation of solid dispersion with different water soluble carriers. Binary systems of Domperidone were prepared with polyvinyl pyrrolidone k-30 (PVP), poloxamer 188 (P188) and polyethylene glycol 6000 (PEG 6000) at different weight ratios using the solvent evaporation method, physical mixtures of the same systems were also used. The effect of the method of preparation was also investigated by preparing some selected formulations using melting method. As P188 is known to inhibit CYP3A4 enzyme which is responsible for hepatic metabolism of many drugs including Domperidone, the effect of incorporation of PVP or PEG 6000 as ternary component to P188 solid dispersion on dissolution rate was also investigated. Formulations were characterized by Fourier transform infrared (FTIR) and Differential scanning calorimetry (DSC). Drug content uniformity and dissolution rate were studied. Solid dispersions showed a better dissolution compared to the pure drug and physical mixtures, with PVP showing the highest dissolution efficiency. As indicated from DSC data, Domperidone was in the amorphous form, which confirmed the better dissolution rate of solid dispersions. Some ternary P188 combinations showed a better enhancement in drug dissolution compared to the optimized P188 binary system. This would present a potential of increasing oral bioavailability of Domperidone by increasing its dissolution rate and by inhibiting its pre-systemic metabolism by the presence of P188.

Improvement of solubility and dissolution properties of clotrimazole by solid dispersions and inclusion complexes.

Solid dispersions of a slightly water-soluble drug, clotrimazole, were prepared in different weight ratios using polyethyleneglycol 4000 and different molecular weight polyvinyl pyrrolidones as carriers. Moreover, binary and ternary ß-cyclodextrin complexes were prepared in different molar ratios. Both solid dispersions and ß-cyclodextrin complexes were prepared by solvent evaporation technique. A phase solubility method was used to evaluate the effect of the tested carriers on the aqueous solubility of clotrimazole. The dissolution of all the preparations was tested using the USP paddle method. The selected solid dispersions and inclusion complexes were characterized by differential scanning calorimetry and X-ray powder diffractometry studies, and results clarified the role of the tested carriers in decreasing the crystallinity of clotrimazole and complexing abilities. Based on physical characters and in vitro drug release pattern, polyvinylpyrrolidone solid dispersions (1:1 weight ratio) and ternary cyclodextrin complexes (clotrimazole-ß-cyclodextrin complexes with either polymer, 1:1 molar ratio) were selected as ideal batches for suppositories. Suppocire AM/50 mg carbopol 940, was chosen as a suppository base and the suppositories were prepared by molding technique. The prepared suppositories were characterized for weight variation, softening time and drug content. All these properties were found to be ideal. The in vitro drug release pattern was determined in citrate buffer (pH 4.5) containing 1% sodium lauryl sulfate. The in vitro release of clotrimazole from its solid dispersions and inclusion complexes incorporated suppositories was markedly improved when compared to the intact drug incorporated suppositories. Polyvinyl pyrrolidone solid dispersions incorporated suppositories were found to possess excellent antifungal activity.