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Aim of the work: To determine the relation between Risperidone plasma concentration and its efficacy in patients with schizophrenia to assess the value of therapeutic drug monitoring in clinical practice. Method: In February 2020, a search was conducted in the period from 2000 to 2020 using Google scholar, Pubmed and Science Direct as search engine. The key words used in this search were Risperidone, plasma concentration, schizophrenia. Articles were selected for inclusion in this search if they involved a test for the correlation between plasma concentration and efficacy. Results: Limited number of studies was found. Among 14 studies, 10 yielded no correlation between Risperidone plasma levels and its efficacy while 4 studies showed positive results. To investigate the relation between Risperidone plasma concentration and clinical response, the most common tools used are HPLC for determination of plasma concentration and PANSS for assessment of clinical response. Conclusion: The majority of studies showed no correlation and therapeutic drug monitoring of Risperidone is still unclear. Further research is needed in this area.

Kariman M AbouElhassan,1,2 Hatem A Sarhan,1 Amal K Hussein,1 Ashraf Taye,3 Yasmin M Ahmed,4 Mohamed A Safwat5 1Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt; 2Faculty of Pharmacy, South Valley University, Qena, 83523, Egypt; 3Department of Pharmacology and Toxicology, Faculty of Pharmacy, South Valley University, Qena, 83523, Egypt; 4Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, 62514, Egypt; 5Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena, 83523, EgyptCorrespondence: Kariman M AbouElhassan, Faculty of Pharmacy, South Valley University, El-Moatakal Street, Qena, Egypt, Tel +20 1008052043, Fax +20 963211279, Email karimanmusalim@yahoo.comBackground: Alzheimer’s disease (AD) is one of the furthermost advanced neurodegenerative disorders resulting in cognitive and behavioral impairment. Citicoline sodium (CIT) boosts the brain’s secretion of acetylcholine, which aids in membrane regeneration and repair. However, it suffers from poor blood–brain barrier (BBB) permeation, which results in lower levels of CIT in the brain.Purpose: This study targeted to encapsulate CIT into novel nano-platform transbilosomes decorated with hyaluronic acid CIT-HA*TBLs to achieve enhanced drug delivery from the nose to the brain.Methods: A method of thin-film hydration was utilized to prepare different formulae of CIT-TBLs using the Box–Behnken design. The optimized formula was then hyuloranated via integration of HA to form the CIT-HA*TBLs formula. Furthermore, AD induction was performed by aluminum chloride (Alcl3), animals were allocated, and brain hippocampus tissue was isolated for ELISA and qRT-PCR analysis of malondialdehyde (MDA), nuclear factor kappa B (NF-kB), and microRNA-137 (miR-137) coupled with immunohistochemical amyloid-beta (Aβ1– 42) expression and histopathological finding.Results: The hyuloranated CIT-HA*TBLs formula, which contained the following ingredients: PL (300 mg), Sp 60 (43.97 mg), and SDC (20 mg). They produced spherical droplets at the nanoscale (178.94 ± 12.4 nm), had a high entrapment efficiency with 74.92± 5.54%, had a sustained release profile of CIT with 81.27 ± 3.8% release, and had ex vivo permeation of CIT with 512.43± 19.58 μg/cm2. In vivo tests showed that CIT-HA*TBL thermogel dramatically reduces the hippocampus expression of miR-137 and (Aβ1– 42) expression, boosting cholinergic neurotransmission and decreasing MDA and NF-kB production. Furthermore, CIT-HA*TBLs thermogel mitigate histopathological damage in compared to the other groups.Conclusion: Succinctly, the innovative loading of CIT-HA*TBLs thermogel is a prospectively invaluable intranasal drug delivery system that can raise the efficacy of CIT in Alzheimer’s management.Keywords: Alzheimer’s disease, transbilosomes, Box–Behnken design, intranasal drug delivery, brain targeting, in vivo study

Many herbal products have been used to control blood glucose level and minimize complications of diabetes mellitus. However, the feasibility of using such herbal product has been hindered due to the lower stability of their extracts and patients incompliance. Objective: An optimized fast disintegrating tablet preparation of spray dried aqueous extract of poly herbal blend has been formulated to maximize the therapeutic activity of such herbal extract. Methods: different ratios of superdisintegrants were evaluated in terms of reducing disintegration time and wetting time of the prepared formulations. The potential of the optimized formula in reducing blood glucose level and promoting wound healing in STZ-induced diabetic rats was determined. Key finding: Oral administration of the optimized formula (F6) had significant superior effect in reducing blood glucose level and promoting wound healing of diabetic rats compared receiving the aqueous extract of the herbal blend (P

The aim of this study was to prepare triamcinolone acetonide (TA)-loaded poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) and poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) micelles as a potential treatment of ocular inflammation. The micelles were evaluated for particle size, drug loading capacity and drug release kinetics. Selected micellar formulations were dispersed into chitosan hydrogel and their anti-inflammatory properties were tested in rabbits using a carrageenan-induced ocular inflammatory model. Particle size ranged from 59.44 ± 0.15 to 64.26 ± 0.55 nm for PEG-b-PCL and from 136.10 ± 1.57 to 176.80 ± 2.25 nm for PEG-b-PLA micelles, respectively. The drug loading capacity was in the range of 6–12% and 15–25% for PEG-b-PCL and PEG-b-PLA micelles, respectively and was dependent on the drug/polymer weight ratio. TA aqueous solubility was increased by 5- and 10-fold after loading into PEG-b-PCL and PEG-b-PLA micelles at a polymer concentration as low as 0.5 mg/mL, respectively. PEG-b-PLA micelles suspended in chitosan hydrogel were able to sustain the drug release where only 42.8 ± 1.6% drug was released in one week. TA/PEG-b-PLA micelles suspended in chitosan hydrogel had better anti-inflammatory effects compared with the plain drug hydrogel or the drug micellar solution. Complete disappearance of the corneal inflammatory changes was observed for the micellar hydrogel. These results confirm the potential of PEG-b-PLA micelles suspended in chitosan hydrogel to enhance the anti-inflammatory properties of triamcinolone acetonide.

A commonly held view is that nanocarriers conjugated to polyethylene glycol (PEG) are non-immunogenic. However, many studies have reported that unexpected immune responses have occurred against PEG-conjugated nanocarriers. One unanticipated response is the rapid clearance of PEGylated nanocarriers upon repeat administration, called the accelerated blood clearance (ABC) phenomenon. ABC involves the production of antibodies toward nanocarrier components, including PEG, which reduces the safety and effectiveness of encapsulated therapeutic agents. Another immune response is the hypersensitivity or infusion reaction referred to as complement (C) activation-related pseudoallergy (CARPA). Such immunogenicity and adverse reactivities of PEGylated nanocarriers may be of potential concern for the clinical use of PEGylated therapeutics. Accordingly, screening of the immunogenicity and CARPA reactogenicity of nanocarrier-based therapeutics should be a prerequisite before they can proceed into clinical studies. This review presents PEGylated liposomes, immunogenicity of PEG, the ABC phenomenon, C activation and lipid-induced CARPA from a toxicological point of view, and also addresses the factors that influence these adverse interactions with the immune system., GRAPHICAL ABSTRACT

Background Post-COVID-19 symptoms and diseases appeared on many survivors from COVID-19 which are similar to that of the post-severe acute respiratory syndrome (SARS) fatigue. Hence, the study aims to investigate and characterise the manifestations which appear after eradication of the coronavirus infection and its relation to disease severity. Method About 287 survivors from COVID-19 were included in the study, each received a questionnaire divided into three main parts starting from subjects' demographic data, data about the COVID-19 status and other comorbidities of the subject, and finally data about post-COVID-19 manifestations. Response surface plots were produced to visualise the link between several factors. Results Only 10.8% of all subjects have no manifestation after recovery from the disease while a large percentage of subjects suffered from several symptoms and diseases. The most common symptom reported was fatigue (72.8%), more critical manifestations like stroke, renal failure, myocarditis and pulmonary fibrosis were reported by a few percent of the subjects. There was a relationship between the presence of other comorbidities and severity of the disease. Also, the severity of COVID-19 was related to the severity of post-COVID-19 manifestations. Conclusion The post-COVID-19 manifestation is largely similar to the post-SARS syndrome. All subjects recovered from COVID-19 should undergo long-term monitoring for evaluation and treatment of symptoms and conditions that might be precipitated with the new coronavirus infection.

Generally, it has been thought that PEG-conjugated nanocarriers are non-immunogenic. However, many reports have revealed that unexpected immune responses occur with such PEG-conjugated nanocarriers. The Most important one is the rapid clearance of PEGylated nanocarriers upon repeated administration which is called accelerated blood clearance phenomenon involving the production of antibodies against nanocarrier components, which reduces the safety and effectiveness of the encapsulated therapeutic agent. Such immunogenicity of PEGylated nanocarriers is a potential concern in the evaluation and clinic use of PEGylated therapeutics. Accordingly, screening of the immunogenicity of nanocarriers-based therapeutics is a prerequisite before their adoption into clinical settings to disclose any possible interactions with immune system. This review gives an overview of PEGylated liposomes, immunogenicity of PEG, explanation of accelerated blood clearance (ABC) phenomenon, its mechanism, various factors affecting it and side effects of PEGylated liposomes.

Mohamed M Ibrahim,1 Abdulla M Abuelmatty,2 Gehan H Mohamed,3 Mohsen A Nasr,4 Amal K Hussein,5 Mohy El Deen Ebaed,6 Hatem A Sarhan5 1Department of Clinical Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt; 2Department of Pharmacy, Jahra Hospital, Jahra, Kuwait; 3Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt; 4Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 5Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt; 6Department of Biochemistry, Egyptian Ministry of Interior, Cairo, Egypt Background: The intensive care unit (ICU) is a center of multidrug-resistant (MDR) pathogens. This is due to overuse of antibiotics in the treatment of critically ill patients. Tigecycline is a broad-spectrum antibiotic that belongs to the glycylcycline group. Tigecycline has been indicated in treatment of complicated intra-abdominal infections (cIAIs) and complicated skin and soft-tissue infections (cSSTIs).Objective: This study was done to discover the best dose regimen of tigecycline in treatment of cSSTIs and cIAIs, especially in patients who are critically ill and obese, for clinical outcomes and safety.Setting: The study was conducted in an adult ICU that consists of 25 beds in a general hospital and was conducted within 2 years. A total of 954 patients were screened in this study.Methods: This was a retrospective cohort study that compared the clinical outcomes of patients: mortality, ICU stay, and safety of using two different dose regimens of tigecycline between patients with different body weight who were treated for infections caused by MDR pathogens in the ICU. The study was conducted within 2 years. All results were collected from patients’ files and were analyzed with SPSS version 20.Main outcome: The study was implemented to figure out the best dose regimen of tigecycline to achieve a reduction in mortality, ICU stay, treatment duration, and secondary septic-shock incidence with minimum side effects in treatment of cSSTIs and cIAIs in patients with different body weight.Results: There was a significant improvement in mortality, ICU stay, recurrent infection by the same organism, duration of tigecycline treatment, number of patients who had first negative culture after starting treatment, secondary bacteremia, and secondary septic shock with patients who used high-dose regimens of tigecycline in different subgroups of body weight, with no significant difference in side effects.Conclusion: The use of high-dose tigecycline resulted in a significant enhancement in all clinical outcomes, especially mortality and ICU stay when used in treatment of overweight and obese patients with cSSTIs and cIAIs. Keywords: tigecycline, obese patients, intensive care unit, complicated intra-abdominal infections, complicated skin and soft-tissue infections&nbsp

Samar Genedy,1 Ahmed Khames,2,3 Amal Hussein,4 Hatem Sarhan4 1Department of Clinical Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; 3Department of Pharmaceutics and Pharmacy Technology, College of Pharmacy, Taif University, Taif, Kingdom of Saudi Arabia; 4Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt Background: Hypertensive disorders are the most common complication in pregnancy which can even lead to maternal mortality. Hydralazine hydrochloride (HHC), a direct-acting vasodilator, is intravenously used as the first-line therapy in controlling hypertension in pregnancy (preeclampsia). It suffers poor oral bioavailability (26%–50%) due to first-pass metabolism.Objective: This work aims for the preparation of HHC rapidly disintegrating sublingual tablets of higher absorption rate, short onset of action, and higher bioavailability for rapid control on blood pressure (BP) in hypertensive emergencies especially preeclampsia.Methods: HHC sublingual tablet mixtures were prepared using starch sodium glycolate and Pharmaburst as super disintegrants at three different levels by direct compression and were subjected to full in vitro evaluation; the drug bioavailability from the optimized sublingual tablet formula was assessed in comparison to conventional oral tablets in rabbits, and the clinical efficacy on controlling BP in induced preeclampsia like mouse model was also studied.Results: The results indicated compatibility of the prepared tablet mixtures, good flow, and acceptable mechanical strength. Sublingual tablet formula containing Pharmaburst (7%) that showed fastest disintegration (21 seconds) and 100% drug release within 5 minutes was selected for further bioavailability and pharmacodynamic studies. The drug bioavailability was significantly increased with Cmax = 28.2767±4.61 µg/mL, AUC(0–α) = 52.85±3.18 µg.h/mL, and Tmax = 0.33±0.011 hour in comparison to 18.0633±23.2 µg/mL, 33.18±5.18 µg.h/mL, and 0.75±0.025 hour for conventional oral tablets. Results of pharmacodynamic studies proved significant rapid control on both systolic and diastolic BP to normal values within only 30 minutes without any significant difference from intravenous data.Conclusion: These results confirm the suitability of the prepared HHC sublingual tablets for use in rapid control on hypertensive crisis especially in pregnant women as an alternate to parenteral administration.Keywords: pre-eclampsia like mouse model, absorption from buccal cavity, preeclampsia, sublingual tablets, hypertension, L-NAME

Acne vulgaris is a common inflammatory skin disorder. It affects the pilosebaceous units followed by an overgrowth by Propionibacterium acne bacteria. Dapsone is a sulfone antibiotic with an anti-inflammatory effect, which is considered to be accountable for its effectiveness in the treatment of acne vulgaris. The present study aims to prepare and evaluate the effectiveness of dapsone niosomes for topical application with an objective to control and prolong the release of the drug with improved skin penetration as a novel formulation for healing of mild to moderate acne vulgaris. Niosomes were formulated by thin film hydration method using different ratios of surfactants (various spans 20, 40, 60 and 80) and cholesterol and were investigated with respect to its shape, size, entrapment efficiency, Fourier transform infrared spectroscopy (FTIR) and in vitro release. Fifteen patients with mild to moderate acne vulgaris were selected and treated with dapsone niosomes as a single topical treatment for their acne lesions. Clinical assessment was done before and after 2 and 8 weeks of treatment. Niosomes containing span 60 showed a higher percentage of drug release after 24 h and greater entrapment efficiency as compared to other formulations. The clinical improvement was noticeable after 2 weeks of treatment with highly significant improvement of acne lesions after 8 weeks of treatment (P < 0.001). Dapsone niosomes is a promising topical formulation for safe, tolerable and effective drug delivery system with minimal side effects apart from mild erythema and post-inflammatory hyperpigmentation. Key words: Dapsone, acne vulgaris, niosomes, topical, clinical application.

Liquorice is one of the commonly used herbs in the field of medicine due to its pharmacological activities. Among these activities, the anti-inflammatory and antiallergic activities that support its use in asthma. This study included 80 asthmatic patients who were classified into two groups, group 1(Placebo group) maintained on inhaled corticosteroids (ICs in moderate to high doses) and long-acting beta agonist (LABA) and received starch capsule (500mg starch) twice daily as placebo and group 2 (active treatment group) maintained on ICs (in moderate to high doses) and LABA and received liquorice extract capsule (500mg equivalent to 100mg glycyrrhizin) taken twice daily. The efficacy of liquorice was measured by estimation of pulmonary function and blood eosinophils %. On the other hand, safety was assessed by blood pressure measurement and determination of serum potassium level. The results revealed that addition of liquorice capsules to ICs and LABA resulted in a non-significant improvement in blood eosinophils (P-value 0.754). However, it resulted in a highly significant improvement in Forced Vital Capacity (FVC) % and Forced Expiratory Volume1 (FEV1) % when compared to group 1 (P-value 0.031.and 0.040 respectively). Regarding liquorice safety, neither Blood pressure (systolic and Diastolic) (SBP and DBP), nor serum K level showed any significant change in patients received liquorice capsules. Conclusion: liquorice in the used dose significantly improved FVC% and FEV1% but did not affect blood eosinophils. There was no significant effect on blood pressure and serum K level, so, this dose is safe with no observed side effects.

Fatma M Mady,1,2 Hanaa Essa,2 Tarek El-Ammawi,3 Hamdy Abdelkader,2 Amal K Hussein2 1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Taibah University, Medina, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt; 3Department of Dermatology, STDs, and Andrology, Minia University Hospital, Minia, Egypt Abstract: Silymarin is a naturally occurring flavonoid drug; evidence from recent research has highlighted its use as a potential treatment for atopic dermatitis (AD). Both poor water solubility and drug permeability have hindered the percutaneous absorption of silymarin. Formulation of silymarin into pluronic-lecithin organogel (PLO) basis for topical skin delivery is the main aim of this work. Six different PLO formulations were prepared containing various pluronic to lecithin ratios using two cosolvent systems of ethyl alcohol and dimethyl sulfoxide. Formulation 2 (20% pluronic and 3% lecithin) was found to be the optimal base for topical delivery of silymarin as it showed optimum pH, viscosity, drug content, and satisfactory in vitro silymarin permeation. The silymarin PLO formulation significantly relieved inflammatory symptoms of AD such as redness, swelling, and inflammation. These findings warrant the ability for application of these novel silymarin PLO formulations as a novel treatment for AD. Keywords: silymarin, pluronic lecithin organogel, atopic dermatitis, skin penetration&nbsp

Mohamed M Ibrahim,1 Tarek Fouad Tammam,2 Mohy El Deen Ebaed,3 Hatem A Sarhan,4 Gamal F Gad,5 Amal K Hussein4 1Department of Clinical Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt; 2Department of Anesthesia and Intensive Care, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 3Department of Biochemistry, Egyptian Ministry of Interior, Cairo, Egypt; 4Department of Pharmaceutics, 5Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia, Egypt Background: Mechanical ventilation support can be the main source of ventilator-associated pneumonia (VAP). VAP is a serious infection that may be associated with dangerous gram-negative bacteria mainly, and it leads to an increase in the mortality in the intensive care unit (ICU). Imipenem is one of the strongest antibiotics now available for treating VAP which is associated with gram-negative and gram-positive bacteria, and it belongs to beta-lactam antibiotic group (carbapenem).Objective: This study tried to investigate the efficacy of imipenem against VAP when it was infused within 180 min versus the efficacy when it was infused within 30–60 min.Setting: This study was conducted in main ICU in general hospital which consists of surgical and medical beds within 2years. One hundred and eighty-seven patients were enrolled on it.Method: This study is a retrospective cohort which was conducted within 2 years. The efficacy of imipenem which was administered by intermittent infusion (30–60 min) within first year was compared with the efficacy of imipenem which was administered by extended infusion (180min) within second year in the field of VAP curing and cost reduction. All data were collected retrospectively from patient medical files and were statistically analyzed by SPSS version 20.Main outcome: The study was designed to measure clinical and cost reduction outcomes, mortality and hospital stay.Results: The results indicated that there is a significant decrease in mortality, number of recurrent infection, and ICU stay length, and the number of mechanical ventilator days was associated with extended imipenem infusion during the second year of the study.Conclusion: The use of imipenem with extended infusion over 3 hours enhances its clinical outcomes in the treatment of VAP. Keywords: carbapenem, imipenem, VAP, extended infusion, intermittent infusion

This study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using {DSC} and FT-IR. The gelation temperature (Tsol-gel), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. {DSC} and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used. {P188} modified the Tsol/gel of {P407} bringing it close to eye temperature (35°C) compared with the formulation containing {P407} alone. Moreover, gels that comprised {P407} and {P188} exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations {PP11} and PP12, the work of adhesion decreased significantly (P < 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control {KT} release as only 48 of the {KT} released within 12 h. In addition, the HET-CAM and {BCOP} tests confirmed the non-irritancy of {KT} loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. {MTT} assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with {KT} showed reasonable and acceptable percent cell viability compared with control samples.

The aim of this work was to formulate chitosan (CS)-based nanoparticles (NPs) loaded with ketorolac tromethamine (KT) intended for topical ocular delivery. NPs were prepared using ionic gelation method incorporating tri-polyphosphate (TPP) as cross-linker. Following the preparation, the composition of the system was optimized in terms of their particle size, zeta potential, entrapment efficiency (EE) and morphology, as well as performing structural characterization studies using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The data suggested that the size of the NPs was affected by CS/TPP ratio where the diameter of the NPs ranged from 108.0 ± 2.4 nm to 257.2 ± 18.6 nm. A correlation between drug EE and the corresponding drug concentration added to the formulation was observed, where the EE of the NPs increased with increasing drug concentration, for up to 10 mg/mL. FT-IR and DSC revealed that KT was dispersed within the NPs where the phosphate groups of TPP were associated with the ammonium groups of CS. The in vitro release profile of KT from CS NPs showed significant differences (p < 0.05) compared to KT solution. Furthermore, mucoadhesion studies revealed adhesive properties of the formulated NPs. The KT-loaded NPs were found to be stable when stored at different storage conditions for a period of 3 months. The ex vivo corneal permeation studies performed on excised porcine eye balls confirmed the ability of NPs in retaining the drug on the eye surface for a relatively longer time. These results demonstrate the potential of CS-based NPs for the ocular delivery of KT.