A practical method for oral administration of isotretinoin in pediatric oncology patient: A case study of neuroblastoma.

INTRODUCTION: Isotretinoin is a synthetic vitamin A derivative, administered off-label as maintenance therapy for neuroblastoma. This report addresses the challenge of administering isotretinoin to children, given its availability as soft gelatin capsules only. CASE REPORT: A 3-year-old boy diagnosed with stage IV neuroblastoma has undergone multimodal therapy, including six cycles of chemotherapy, followed by tumor resection and radiotherapy. Later, he was initiated on immunotherapy and prescribed isotretinoin 50 mg orally twice daily for two weeks, before each immunotherapy cycle. Isotretinoin is not available in liquid formulation and the patient could not swallow isotretinoin capsules. Therefore, pharmacist counseling was required to ensure appropriate administration of the drug. MANAGEMENT AND OUTCOMES: The patient's parents were instructed to pierce prescribed capsules, and empty and dilute their contents into a small glass containing olive oil after taking safety measures. Isotretinoin's stability in olive oil for 72 h was compared using high-performance liquid chromatography to its stability in soybean oil. The recovery rates were 98.62% and 98.3%, respectively. Drug miscibility was not an issue as isotretinoin is lipophilic. Therefore, it could be administered easily without considerable remaining on the interior wall of the glass. DISCUSSION: To the best of our knowledge, this is the first report that suggests a practical method for administering isotretinoin in liquid form, particularly in pediatric oncology patients. Isotretinoin was noted to be stable in olive oil and its exposure to light and oxygen would not be an issue given the short time from preparation to administration and the low emphasis on exposure by the manufacturer when such a method is recommended.

Editorial: Nanomedicine-Based Drug Delivery Systems: Recent Developments and Future Prospects.

Since the discovery of nanomedicine-based drug delivery carriers such as nanoparticles, liposomes, and self-nanoemulsifying drug delivery systems (SNEDDS), enormous progress has been achieved in the field of innovative active biomolecule drug delivery systems [...].

Solubility and Thermodynamics Data of Cabozantinib Malate in Various Aqueous Solutions of Dimethyl Sulfoxide at Different Temperatures.

Cabozantinib malate (CBZM), a new anticancer medication, has been studied for its solubility and thermodynamic properties in a variety of {dimethyl sulfoxide (DMSO) + water (H2O)} mixtures at 298.2-318.2 K and 101.1 kPa. Using the shake flask technique, the solubility of CBZM was assessed and the results were correlated to the van't Hoff, Apelblat, Buchowski-Ksiazczak λh, Yalkowsky-Roseman, Jouyban-Acree, and Jouyban-Acree-van't Hoff models. There was a significant correlation between the experimental CBZM solubility data and all computational models, as evidenced by the error values for all computational models being less than 5.0%. Temperature and DMSO mass percentage improved the CBZM mole fraction solubility in the cosolvent solutions of {DMSO + H2O}. At 318.2 K, pure DMSO had the highest mole fraction solubility of CBZM (4.38 × 10-2), whereas pure H2O had the lowest mole fraction solubility (2.24 × 10-7 at 298.2 K). The positive values of computed thermodynamic parameters indicated that the dissolution of CBZM was endothermic and entropy-driven in all of the {DMSO + H2O} solutions investigated. It was found that the CBZM solvation in {DMSO + H2O} solutions is governed by enthalpy. When compared to CBZM-H2O, CBZM-DMSO showed the highest molecular interactions. The findings of this investigation demonstrated that DMSO has a great deal of potential for CBZM solubilization in H2O.

Solubility and Thermodynamic Analysis of Isotretinoin in Different (DMSO + Water) Mixtures.

The solubility and solution thermodynamics of isotretinoin (ITN) (3) in numerous {dimethyl sulfoxide (DMSO) (1) + water (H2O) (2)} combinations were studied at 298.2-318.2 K under fixed atmospheric pressure of 101.1 kPa. A shake flask methodology was used to determine ITN solubility, and correlations were made using the "van't Hoff, Apelblat, Buchowski-Ksiazczak λh, Yalkowsky-Roseman, Jouyban-Acree, and Jouyban-Acree-van't Hoff models". In mixtures of {(DMSO (1) + H2O (2)}, the solubility of ITN in mole fractions was enhanced with the temperature and DMSO mass fraction. The mole fraction solubility of ITN was highest in neat DMSO (1.02 × 10-1 at 318.2 K) and lowest in pure H2O (3.14 × 10-7 at 298.2 K). The output of computational models revealed good relationships between the solubility data from the experiments. The dissolution of ITN was "endothermic and entropy-driven" in all of the {(DMSO (1) + H2O (2)} mixtures examined, according to the positive values of measured thermodynamic parameters. Enthalpy was discovered to be the driving force behind ITN solvation in {(DMSO (1) + H2O (2)} combinations. ITN-DMSO displayed the highest molecular interactions when compared to ITN-H2O. The outcomes of this study suggest that DMSO has a great potential for solubilizing ITN in H2O.

A Rapid and Sensitive Stability-Indicating Eco-Friendly HPTLC Assay for Fluorescence Detection of Ergotamine.

Eco-friendly liquid chromatographic methods for measuring ergotamine (EGT) are scant in the published database. Accordingly, the goal of the current study was to develop a high-performance thin-layer chromatography (HPTLC) method for fluorescence detection of EGT in commercially available tablets. This approach was based on the application of ethyl alcohol-water (80:20 v/v) as the eco-friendly eluent mixture. The fluorescence detection of EGT was carried out at 322 nm. The greenness score of the present approach was evaluated by "Analytical GREENness (AGREE)" technology. The present approach for measuring EGT in the 25-1000 ng band-1 range was linear. The present assay for fluorescence detection of EGT was validated successfully by ICH guidelines for various parameters. The method was found to be rapid, sensitive, eco-friendly, and stability-indicating. The computed AGREE index for the current strategy was 0.84, displaying outstanding greenness features. The present methodology successfully separated the EGT degradation products under forced-degradation circumstances, exhibiting its stability-indicating qualities and selectivity. An amount of 99.33% of EGT was found in commercial formulations, indicating the validity of the current method for pharmaceutical analysis of EGT in commercial products. The results showed that EGT in commercial products might be regularly measured by the existing method.

Insight into Structure Activity Relationship of DPP-4 Inhibitors for Development of Antidiabetic Agents.

This article sheds light on the various scaffolds that can be used in the designing and development of novel synthetic compounds to create DPP-4 inhibitors for the treatment of type 2 diabetes mellitus (T2DM). This review highlights a variety of scaffolds with high DPP-4 inhibition activity, such as pyrazolopyrimidine, tetrahydro pyridopyrimidine, uracil-based benzoic acid and esters, triazole-based, fluorophenyl-based, glycinamide, glycolamide, ß-carbonyl 1,2,4-triazole, and quinazoline motifs. The article further explains that the potential of the compounds can be increased by substituting atoms such as fluorine, chlorine, and bromine. Docking of existing drugs like sitagliptin, saxagliptin, and vildagliptin was done using Maestro 12.5, and the interaction with specific residues was studied to gain a better understanding of the active sites of DPP-4. The structural activities of the various scaffolds against DPP-4 were further illustrated by their inhibitory concentration (IC50) values. Additionally, various synthesis schemes were developed to make several commercially available DPP4 inhibitors such as vildagliptin, sitagliptin and omarigliptin. In conclusion, the use of halogenated scaffolds for the development of DPP-4 inhibitors is likely to be an area of increasing interest in the future.

Erlotinib-Loaded Dendrimer Nanocomposites as a Targeted Lung Cancer Chemotherapy.

Lung cancer is the main cause of cancer-related mortality globally. Erlotinib is a tyrosine kinase inhibitor, affecting both cancerous cell proliferation and survival. The emergence of oncological nanotechnology has provided a novel drug delivery system for erlotinib. The aims of this current investigation were to formulate two different polyamidoamine (PAMAM) dendrimer generations-generation 4 (G4) and generation 5 (G5) PAMAM dendrimer-to study the impact of two different PAMAM dendrimer formulations on entrapment by drug loading and encapsulation efficiency tests; to assess various characterizations, including particle size distribution, polydispersity index, and zeta potential; and to evaluate in vitro drug release along with assessing in situ human lung adenocarcinoma cell culture. The results showed that the average particle size of G4 and G5 nanocomposites were 200 nm and 224.8 nm, with polydispersity index values of 0.05 and 0.300, zeta potential values of 11.54 and 4.26 mV of G4 and G5 PAMAM dendrimer, respectively. Comparative in situ study showed that cationic G4 erlotinib-loaded dendrimer was more selective and had higher antiproliferation activity against A549 lung cells compared to neutral G5 erlotinib-loaded dendrimers and erlotinib alone. These conclusions highlight the potential effect of cationic G4 dendrimer as a targeting-sustained-release carrier for erlotinib.

Current and future prospective of pharmaceutical manufacturing in Saudi Arabia.

This observational descriptive study that was carried out with the objective of exploring the contribution of the local pharmaceutical industry to the Saudi drug security. Using a drug formulary provided from the Saudi Food and Drug Authority, containing all registered pharmaceutical products available in Saudi Arabia, we extracted information about drug class, drug type, country and place of manufacturing, shelf-life and price. Results showed that the majority of drugs in the market are manufactured in Europe (43.86%), followed by Saudi Arabia (22.55%), China and India (20.47%), Americas (10.24%), and other nations (2.61%). Most of the manufactured drugs were prescription drugs (90.62%). In this work, the local pharmaceutical industry with the highest percentage of contribution to local drug security was Pharmaceutical Solution Industries (PSI), representing the 5% of the items available in the Saudi market. The second highest percentage was 4% by TABUK Pharmaceutical Manufacturing CO., followed by SPIMACO (3%), JAMJOOM pharmaceutical company (2%), Riyadh pharma (2%), and Jazeera pharmaceutical industries (2%). In addition, results from this study provide information about the most essential pharmaceutical products that needs to be nationally manufactured or increased in production in order to rise the contribution of local pharmaceutical industries in Saudi drug security. Unfortunately, the small contribution of the Saudi pharmaceutical industry in local drug security increases the burden on the Kingdom's annual budget due to the over-reliance on international pharmaceuticals.

Chitosan loaded RNA polymerase inhibitor nanoparticles increased attenuation in toxin release from Streptococcus pneumonia.

Background: Multidrug-resistant (MDR) bacterial infections have become an emerging health concern around the world. Antibiotics resistance among S. pneumoniae strains increased recently contributing to increase in incidence of pneumococcal infection. This necessitates the discovery of novel antipnemococcal such as compound C3-005 which target the interaction between RNA polymerase and σ factors. Chitosan nanoparticles (CNPs) exhibited antibacterial activity including S. pneumonia. Therefore, the aims of the current investigation were to formulate CNPs loaded with C3-005 and characteristic their antimicrobial properties against S. pneumonia. Methods: The CNPs and C3-005 loaded CNPs were produced utilizing ionic gelation method, and their physicochemical characteristics including particle size, zeta potential, polydispersity index (PDI), encapsulation efficiency (EE%), and in vitro release profile were studied. Both differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR) were used for chemical characterization. The synthesized NPs' minimum inhibitory concentration (MIC) was determined using killing assay and broth dilution method, and their impact on bacteria induced hemolysis were also studied. Results: The NPs encapsulating C3-005 were successfully prepared with particle size of 343.5 nm ± 1.3, zeta potential of 29.8 ± 0.37, and PDI of 0.20 ± 0.03. 70 % of C3-005 were encapsulated in CNPs and sustained release pattern of C3-005 from CNPs was revealed by an in vitro release study. CNPs containing C3-005 exhibited higher antipnomcoccal activity with MIC50 of 30 µg/ml when compared with C3-005 and empty CNPs alone. The prepared C3-CNPs showed a reduction of bacterial hemolysis in a concentration-related (dependent) manner and was higher than C3-005 alone. Conclusions: The findings of this study showed the potential for using C3-005 loaded CNPs to treat pneumococcal infection.

A review of radical and non-radical degradation of amoxicillin by using different oxidation process systems.

Pharmaceutical compounds have piqued the interest of researchers due to an increase in their demand, which increases the possibility of leakage into the environment. Amoxicillin (AMX) is a penicillin derivative used for the treatment of infections caused by gram-positive bacteria. AMX has a low metabolic rate in the human body, and around 80-90% is unmetabolized. As a result, AMX residuals should be treated immediately to avoid further accumulation in the environment. Advanced oxidation process techniques are an efficient way to degrade AMX. This review attempts to collect, organize, summarize, and analyze the most up to date research linked to the degradation of AMX by different advanced oxidation process systems including photocatalytic, ultrasonic, electro-oxidation, and advanced oxidation process-based on partials. The main topics investigated in this review are degradation mechanism, degradation efficiency, catalyst stability, the formation of AMX by-products and its toxicity, in addition, the influence of different experimental conditions was discussed such as pH, temperature, scavengers, the concentration of amoxicillin, oxidants, catalyst, and doping ratio. The degradation of AMX could be inhibited by very high values of pH, temperature, AMX concentration, oxidants concentration, catalyst concentration, and doping ratio. Several AMX by-products were discovered after oxidation treatment, and several of them had lower or same values of LC50 (96 h) fathead minnow of AMX itself, such as m/z 384, 375, 349, 323, 324, 321, 318, with prediction values of 0.70, 1.10, 1.10 0.42, 0.42, 0.42, and 0.42 mg/L, respectively. We revealed that there is no silver bullet system to oxidize AMX from an aqueous medium. However, it is recommended to apply hybrid systems such as Photo-electro, Photo-Fenton, Electro-Fenton, etc. Hybrid systems are capable to cover the drawbacks of the single system. This review may provide important information, as well as future recommendations, for future researchers interested in treating AMX using various AOP systems, allowing them to improve the applicability of their systems and successfully oxidize AMX from an aqueous medium.

Green NP-HPTLC and green RP-HPTLC methods for the determination of thymoquinone: A contrast of validation parameters and greenness assessment.

INTRODUCTION: Thymoquinone (TQ) is a naturally derived bioactive compound with several therapeutic effects. OBJECTIVE: The highly sensitive, rapid and green normal-phase (NP)/reversed-phase (RP) high-performance thin-layer chromatography (HPTLC) densitometry technique was developed for the determination of TQ in various plant extracts of different geographical regions, commercial capsules, creams and essential oils. METHODOLOGY: The NP densitometry estimation of TQ was performed using a cyclohexane-ethyl acetate (90:10, v/v) green solvent system, while, the RP-densitometry estimation of TQ was performed using an ethanol-water (80:20, v/v) green solvent system. The estimation of TQ was conducted at 259 nm. RESULTS: The NP and RP densitometry techniques were observed linear in the range of 25-1000 and 50-600 ng/band, respectively. All validation parameters such as accuracy, precision, robustness and sensitivity of NP/RP densitometry were observed within the limit of regulatory requirements and hence found to be suitable for the determination of TQ. The TQ contents were found to be highest in the Saudi Arabian extract followed by the Syrian extract, Indian extract, commercial capsules, commercial creams, Jordanian extract, Egyptian extract, Palestinian extract and commercial essential oils using NP densitometry. The TQ contents were found in same order using RP densitometry, but they were much lower than those recorded using NP densitometry. The Analytical GREEnness (AGREE) scores of NP and RP densitometry were found to be 0.82 and 0.84, respectively, suggesting an excellent greenness profile. CONCLUSIONS: Based on these results, NP/RP densitometry was found to be suitable for the pharmaceutical assay of TQ.

Tricyclodecan-9-yl-Xanthogenate (D609): Mechanism of Action and Pharmacological Applications.

Tricyclodecan-9-yl xanthogenate (D609) is a synthetic tricyclic compound possessing a xanthate group. This xanthogenate compound is known for its diverse pharmacological properties. Over the last three decades, many studies have reported the biological activities of D609, including antioxidant, antiapoptotic, anticholinergic, anti-tumor, anti-inflammatory, anti-viral, anti-proliferative, and neuroprotective activities. Its mechanism of action is extensively attributed to its ability to cause the competitive inhibition of phosphatidylcholine (PC)-specific phospholipase C (PC-PLC) and sphingomyelin synthase (SMS). The inhibition of PCPLC or SMS affects secondary messengers with a lipidic nature, i.e., 1,2-diacylglycerol (DAG) and ceramide. Various in vitro/in vivo studies suggest that PCPLC and SMS inhibition regulate the cell cycle, block cellular proliferation, and induce differentiation. D609 acts as a pro-inflammatory cytokine antagonist and diminishes Aß-stimulated toxicity. PCPLC enzymatic activity essentially requires Zn2+, and D609 might act as a potential chelator of Zn2+, thereby blocking PCPLC enzymatic activity. D609 also demonstrates promising results in reducing atherosclerotic plaque formation, post-stroke cerebral infarction, and cancer progression. The present compilation provides a comprehensive mechanistic insight into D609, including its chemistry, mechanism of action, and regulation of various pharmacological activities.

Silk Fibroin as an Efficient Biomaterial for Drug Delivery, Gene Therapy, and Wound Healing.

Silk fibroin (SF), an organic material obtained from the cocoons of a silkworm Bombyx mori, is used in several applications and has a proven track record in biomedicine owing to its superior compatibility with the human body, superb mechanical characteristics, and its controllable propensity to decay. Due to its robust biocompatibility, less immunogenic, non-toxic, non-carcinogenic, and biodegradable properties, it has been widely used in biological and biomedical fields, including wound healing. The key strategies for building diverse SF-based drug delivery systems are discussed in this review, as well as the most recent ways for developing functionalized SF for controlled or redirected medicines, gene therapy, and wound healing. Understanding the features of SF and the various ways to manipulate its physicochemical and mechanical properties enables the development of more effective drug delivery devices. Drugs are encapsulated in SF-based drug delivery systems to extend their shelf life and control their release, allowing them to travel further across the bloodstream and thus extend their range of operation. Furthermore, due to their tunable properties, SF-based drug delivery systems open up new possibilities for drug delivery, gene therapy, and wound healing.

Solubility and Thermodynamic Data of Febuxostat in Various Mono Solvents at Different Temperatures.

This study examines the solubility and thermodynamics of febuxostat (FBX) in a variety of mono solvents, including "water, methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO)" at 298.2−318.2 K and 101.1 kPa. The solubility of FBX was determined using a shake flask method and correlated with "van't Hoff, Buchowski-Ksiazczak λh, and Apelblat models". The overall error values for van't Hoff, Buchowski-Ksiazczak λh, and Apelblat models was recorded to be 1.60, 2.86, and 1.14%, respectively. The maximum mole fraction solubility of FBX was 3.06 × 10−2 in PEG-400 at 318.2 K, however the least one was 1.97 × 10−7 in water at 298.2 K. The FBX solubility increased with temperature and the order followed in different mono solvents was PEG-400 (3.06 × 10−2) > THP (1.70 × 10−2) > 2-BuOH (1.38 × 10−2) > 1-BuOH (1.37 × 10−2) > IPA (1.10 × 10−2) > EtOH (8.37 × 10−3) > EA (8.31 × 10−3) > DMSO (7.35 × 10−3) > MeOH (3.26 × 10−3) > PG (1.88 × 10−3) > EG (1.31 × 10−3) > water (1.14 × 10−6) at 318.2 K. Compared to the other combinations of FBX and mono solvents, FBX-PEG-400 had the strongest solute-solvent interactions. The apparent thermodynamic analysis revealed that FBX dissolution was "endothermic and entropy-driven" in all mono solvents investigated. Based on these findings, PEG-400 appears to be the optimal co-solvent for FBX solubility.

Simultaneous Estimation of Escitalopram and Clonazepam in Tablet Dosage Forms Using HPLC-DAD Method and Optimization of Chromatographic Conditions by Box-Behnken Design.

The study aimed to develop a new reverse-phase high-performance liquid chromatography (RP-HPLC) method with diode array detection (DAD) detection for simultaneous estimation of escitalopram (EST) and clonazepam (CZP) in tablet dosage forms with a quality by design (QbD) approach. The chromatographic conditions were optimized by Box-Behnken design (BBD) and developed method was validated for the linearity, system suitability, accuracy, precision, robustness, sensitivity, and solution stability according to International Council for Harmonization (ICH) guidelines. EST and CZP standard drugs peaks were separated at retention times of 2.668 and 5.046 min by C-18 column with dimension of 4.6 × 100 mm length and particle size packing 2.5 µm. The mobile phase was methanol: 0.1% orthophosphoric acid (OPA) (25:75, v/v), with a flow rate of 0.7 mL/min at temperature of 26 °C. The sample volume injected was 20 µL and peaks were detected at 239 nm. Using the standard calibration curve, the % assay of marketed tablet was founded 98.89 and 98.76 for EST and CZP, respectively. The proposed RP-HPLC method was able to detect EST and CZP in the presence of their degradation products, indicating the stability-indicating property of the developed RP-HPLC method. The validation parameter's results in terms of linearity, system suitability, accuracy, precision, robustness, sensitivity, and solution stability were in an acceptable range as per the ICH guidelines. The newly developed RP-HPLC method with QbD application is simple, accurate, time-saving, and economic.

A Review on the Main Phytoconstituents, Traditional Uses, Inventions, and Patent Literature of Gum Arabic Emphasizing Acacia seyal.

Acacia seyal is an important source of gum Arabic. The availability, traditional, medicinal, pharmaceutical, nutritional, and cosmetic applications of gum acacia have pronounced its high economic value and attracted global attention. In addition to summarizing the inventions/patents applications related to gum A. seyal, the present review highlights recent updates regarding its phytoconstituents. Traditional, cosmetic, pharmaceutical, and medicinal uses with the possible mechanism of actions have been also reviewed. The patent search revealed the identification of 30 patents/patent applications of A. seyal. The first patent related to A. seyal was published in 1892, which was related to its use in the prophylaxis/treatment of kidney and bladder affections. The use of A. seyal to treat cancer and osteoporosis has also been patented. Some inventions provided compositions and formulations containing A. seyal or its ingredients for pharmaceutical and medical applications. The inventions related to agricultural applications, food industry, cosmetics, quality control of gum Arabic, and isolation of some chemical constituents (L-rhamnose and arabinose) from A. seyal have also been summarized. The identification of only 30 patents/patent applications from 1892 to 15 November 2021 indicates a steadily growing interest and encourages developing more inventions related to A. seyal. The authors recommend exploring these opportunities for the benefit of society.

Determination of Thymol in Commercial Formulation, Essential Oils, Traditional, and Ultrasound-Based Extracts of Thymus vulgaris and Origanum vulgare Using a Greener HPTLC Approach.

In the literature, greener analytical approaches for determining thymol in its commercial formulations, plant-based phytopharmaceuticals, and biological fluids are scarce. As a result, the goal of this study is to develop and validate a normal-phase "high-performance thin-layer chromatography (HPTLC)" method for determining thymol in commercial formulations, essential oils, traditional extracts (TE), and ultrasound-based extracts (UBE) of Thymus vulgaris and Origanum vulgare obtained from various geographical regions. The greener mobile phase for thymol analysis was a binary combination of cyclohexane and ethyl acetate (85:15, v/v). The derivatized densitometric analysis of thymol was carried out under visible mode at 530 nm utilizing anisaldehyde-sulfuric acid as a derivatizing/visualizing agent. In the 10-2000 ng/band range, the greener normal-phase HPTLC method was linear. Furthermore, for thymol analysis, the proposed analytical approach was simple, quick, inexpensive, accurate, precise, robust, sensitive, and greener. The thymol contents in commercial formulation were computed as 7.61% w/w. In general, the thymol contents were maximum in essential oils of T. vulgaris and O. vulgare compared to the other sample matrices studied. The thymol contents of TE of T. vulgaris and O. vulgare of different geographical regions were significantly low compared to their UBE extract. Using 12 distinct components of green analytical chemistry, the overall "analytical GREEnness (AGREE)" scale for the proposed analytical approach was computed 0.79, showing the good greener nature of the proposed analytical approach. Overall, the greener normal-phase HPTLC technique was found to be reliable for determining thymol in commercial formulations and plant-based phytopharmaceuticals.

Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Apremilast: In Vitro Evaluation and Pharmacokinetics Studies.

Psoriatic arthritis is an autoimmune disease of the joints that can lead to persistent inflammation, irreversible joint damage and disability. The current treatments are of limited efficacy and inconvenient. Apremilast (APR) immediate release tablets Otezla® have 20-33% bioavailability compared to the APR absolute bioavailability of 73%. As a result, self-nanoemulsifying drug delivery systems (SNEDDS) of APR were formulated to enhance APR's solubility, dissolution, and oral bioavailability. The drug assay was carried out using a developed and validated HPLC method. Various thermodynamic tests were carried out on APR-SNEDDS. Stable SNEDDS were characterized then subjected to in vitro drug release studies via dialysis membrane. The optimum formulation was F9, which showed the maximum in vitro drug release (94.9%) over 24 h, and this was further investigated in in vivo studies. F9 was composed of 15% oil, 60% Smix, and 25% water and had the lowest droplet size (17.505 ± 0.247 nm), low PDI (0.147 ± 0.014), low ZP (-13.35 mV), highest %T (99.15 ± 0.131) and optimum increases in the relative bioavailability (703.66%) compared to APR suspension (100%) over 24 h. These findings showed that APR-SNEDDS is a possible alternative delivery system for APR. Further studies are warranted to evaluate the major factors that influence the encapsulation efficiency and stability of APR-containing SNEDDS.

Development and Optimization of Ciprofloxacin HCl-Loaded Chitosan Nanoparticles Using Box-Behnken Experimental Design.

Various chitosan (CS)-based nanoparticles (CS-NPs) of ciprofloxacin hydrochloride (CHCl) have been investigated for therapeutic delivery and to enhance antimicrobial efficacy. However, the Box-Behnken design (BBD)-supported statistical optimization of NPs of CHCl has not been performed in the literature. As a result, the goal of this study was to look into the key interactions and quadratic impacts of formulation variables on the performance of CHCl-CS-NPs in a systematic way. To optimize CHCl-loaded CS-NPs generated by the ionic gelation process, the response surface methodology (RSM) was used. The BBD was used with three factors on three levels and three replicas at the central point. Tripolyphosphate, CS concentrations, and ultrasonication energy were chosen as independent variables after preliminary screening. Particle size (PS), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), and in vitro release were the dependent factors (responses). Prepared NPs were found in the PS range of 198-304 nm with a ZP of 27-42 mV. EE and drug release were in the range of 23-45% and 36-61%, respectively. All of the responses were optimized at the same time using a desirability function based on Design Expert® modeling and a desirability factor of 95%. The minimum inhibitory concentration (MIC) of the improved formula against two bacterial strains, Pseudomonas aeruginosa and Staphylococcus aureus, was determined. The MIC of the optimized NPs was found to be decreased 4-fold compared with pure CHCl. The predicted and observed values for the optimized formulation were nearly identical. The BBD aided in a better understanding of the intrinsic relationship between formulation variables and responses, as well as the optimization of CHCl-loaded CS-NPs in a time- and labor-efficient manner.

Thermodynamic Solubility Profile of Temozolomide in Different Commonly Used Pharmaceutical Solvents.

The solubility parameters, and solution thermodynamics of temozolomide (TMZ) in 10 frequently used solvents were examined at five different temperatures. The maximum mole fraction solubility of TMZ was ascertained in dimethyl sulfoxide (1.35 × 10-2), followed by that in polyethylene glycol-400 (3.32 × 10-3) > Transcutol® (2.89 × 10-3) > ethylene glycol (1.64 × 10-3) > propylene glycol (1.47 × 10-3) > H2O (7.70 × 10-4) > ethyl acetate (5.44 × 10-4) > ethanol (1.80 × 10-4) > isopropyl alcohol (1.32 × 10-4) > 1-butanol (1.07 × 10-4) at 323.2 K. An analogous pattern was also observed for the other investigated temperatures. The quantitated TMZ solubility values were regressed using Apelblat and Van't Hoff models and showed overall deviances of 0.96% and 1.33%, respectively. Apparent thermodynamic analysis indicated endothermic, spontaneous, and entropy-driven dissolution of TMZ in all solvents. TMZ solubility data may help to formulate dosage forms, recrystallize, purify, and extract/separate TMZ.