Systematic DOE Approach for Dry Granulation Study at Early Clinical Stage of Novel Drugs: An Industrial Case.

In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.

Micro-encapsulation of garlic oil using esterified-wheat porous starch and whey protein isolate: Physicochemical properties, release behavior during in vitro digestion.

The study aimed to inhibit the stimulating impact of garlic oil (GO) on the stomach and attain high release in the intestine during digestion. So, wheat porous starch (WPS) was modified with octenyl succinic acid (OSA) and malic acid (MA) to obtain esterified WPS, OWPS and MWPS, respectively. The differences in physicochemical, encapsulation, and digestive properties of two GO microcapsules, WPI/OWPS/GO and WPI/MWPS/GO microcapsules produced by using OWPS and MWPS as variant carrier materials and whey protein isolate (WPI) as the same coating agent, were compared. The results found that OWPS had greater amphiphilicity, while MWPS had better hydrophobicity and anti-digestive ability than WPS. Encapsulation efficiency of WPI/OWPS/GO (94.67 %) was significantly greater than WPI/MWPS/GO (91.44 %). The digestion inhibition and low GO release (approximately 23 %) of WPI/OWPS/GO and WPI/MWPS/GO microcapsules in the gastric phase resulted from the protective effect of WPI combined with the good adsorption and lipophilicity of OWPS and MWPS. Especially, WPI/OWPS/GO microcapsule was relatively stable in the gastric phase and had sufficient GO release (67.24 %) in the intestinal phase, which was significantly higher than WPI/MWPS/GO microcapsule (56.03 %), benefiting from the adsorption and digestive properties of OWPS, and resulting in a total cumulative GO release rate of 90.86 %.

Formulation development of tazarotene-loaded PLGA nanoparticles for follicular delivery in the treatment of inflammatory skin diseases.

Tazarotene is a widely prescribed topical retinoid for acne vulgaris and plaque psoriasis and is associated with skin irritation, dryness, flaking, and photosensitivity. In vitro permeation of tazarotene was studied across the dermatomed human and full-thickness porcine skin. The conversion of tazarotene to the active form tazarotenic acid was studied in various skin models. Tazarotene-loaded PLGA nanoparticles were prepared using the nanoprecipitation technique to target skin and hair follicles effectively. The effect of formulation and processing variables on nanoparticle properties, such as particle size and drug loading, was investigated. The optimized nanoparticle batches with particle size <500 µm were characterized further for FT-IR analysis, which indicated no interactions between tazarotene and PLGA. Scanning electron microscopy analysis showed uniform, spherical, and non-agglomerated nanoparticles. In vitro release study using a dialysis membrane indicated a sustained release of 40-70 % for different batches over 36 h, following a diffusion-based release mechanism based on the Higuchi model. In vitro permeation testing (IVPT) in full-thickness porcine skin showed significantly enhanced follicular and skin delivery from nanoparticles compared to solution. The presence of tazarotenic acid in the skin from tazarotene nanoparticles indicated the effectiveness of nanoparticle formulations in retaining bioconversion ability and targeting follicular delivery.

Microencapsulation of highly concentrated polyphenolic compounds from purple corn pericarp by spray-drying with various biomacromolecules.

Colored corn pericarp contains unusually high amounts of industrially valuable phytochemicals, such as anthocyanins, flavanols, flavonoids, and phenolic acids. Polyphenols were extracted in an aqueous solution and spray-dried to produce microencapsulates using four carrier materials, namely, maltodextrin (MD), gum arabic (GA), methylcellulose (MC), and skim milk powder (SMP) at three concentrations (1, 2, and 3 %, respectively). The encapsulates were evaluated for their polyphenolic contents using spectrophotometric techniques and HPLC analyses, and their antioxidant properties were evaluated using four different assays. The physicochemical properties of encapsulates were analyzed by measuring the zeta potential (ZP), particle size distribution, water solubility index (WSI), water absorption index (WAI), and color parameters. Structural and thermal properties were evaluated using Fourier transform infrared spectroscopy (FTIR), optical profilometry, and differential scanning calorimetry (DSC) analyses. Comparative analysis of structural characteristics, particle size distribution, zeta potential, WSI, WAI, and aw of the samples confirmed the successful formulation of encapsulates. The microencapsulates embedded with 1 % concentrations of MD, MC, GA, or SMP retained polyphenolic compounds and exhibited noteworthy antioxidant properties. The samples encapsulated with GA or MD (1 %) demonstrated superior physicochemical, color, and thermal properties. Comprehensive metabolomic analysis confirmed the presence of 38 phytochemicals in extracts validating the spray-drying process.

Designing starch-based fenofibrate formulations using the melting method.

Fenofibrate (FNF) is used to treat hyperlipidemia. However, FNF is a poorly water-soluble drug, and the dosage of commercial products is relatively high at 160 mg in a Lipidil® tablet. Therefore, this study aimed to develop an FNF-solid dispersion (SD) that solubilizes and stabilizes FNF. The melting method that uses the low melting point of FNF was employed. The dissolution percentage of FNF in the optimal formulation (SD2) increased by 1.2-, 1.3-, and 1.3-fold at 5 min compared to that of Lipidil® and increased by 2.0-, 2.1-, and 2.0-fold compared to the pure FNF in pH 1.2 media, distilled water, and pH 6.8 buffer, which included 0.025 M sodium lauryl sulfate, respectively. The SD2 formulation showed a dissolution percentage of nearly 100 % in all dissolution media after 60 min. The physicochemical properties of the SD2 formulation exhibited slight changes in the melting point and crystallinity of FNF. Moreover, the stability of the SD2 formulation was maintained for six months. In particular, it was challenging to secure stability when starch#1500 was excluded from the SD2 formulation. In conclusion, the dissolution percentage of FNF in the SD2 formulation was improved owing to the weak binding force between FNF and the excipients, stability was secured, and favorable results are expected in future animal experiments.

Stabilization of zein nanoparticles with tween-80 and fucoidan for encapsulation of eugenol via a nozzle simulation chip.

Eugenol (EU), a natural bioactive compound found in various plants, offers numerous health benefits, but its application in the food and pharmaceutical industry is limited by its high volatility, instability, and low water solubility. Therefore, this study aimed to utilize the surface coating technique to develop zein-tween-80-fucoidan (Z-T-FD) composite nanoparticles for encapsulating eugenol using a nozzle simulation chip. The physicochemical characteristics of the composite nanoparticles were examined by varying the weight ratios of Z, T, and FD. Results showed that the Z-T-FD weight ratio of 5:1:15 exhibited excellent colloidal stability under a range of conditions, including pH (2-8), salt concentrations (10-500 mmol/L), heating (80 °C), and storage (30 days). Encapsulation of EU into Z-T-FD nanoparticles (0.5:5:1:15) resulted in an encapsulation efficiency of 49.29 ± 1.00%, loading capacity of 0.46 ± 0.05%, particle size of 205.01 ± 3.25 nm, PDI of 0.179 ± 0.006, and zeta-potential of 37.12 ± 1.87 mV. Spherical structures were formed through hydrophobic interaction and hydrogen bonding, as confirmed by Fourier transform infrared spectroscopy and molecular docking. Furthermore, the EU-Z-T-FD (0.5:5:1:15) nanoparticles displayed higher in vitro antioxidant properties (with DPPH and ABTS radical scavenging properties at 75.28 ± 0.16% and 39.13 ± 1.22%, respectively), in vitro bioaccessibility (64.78 ± 1.37%), and retention rates under thermal and storage conditions for EU compared to other formulations. These findings demonstrate that the Z-T-FD nanoparticle system can effectively encapsulate, protect, and deliver eugenol, making it a promising option for applications in the food and pharmaceutical industries.

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

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

Effect of Formulation Parameters on Enalapril Maleate Mucoadhesive Buccal Tablet Using Quality by Design (QbD) Approach.

The buccal route has great prospects and possible benefits for the administration of drugs systemically. The present study involves designing, developing and optimising the buccal tablet formulation of Enalapril Maleate (EM) by using the QbD approach. We prepared the EM buccal tablets using the dry granulation method. In the QTPP profile, the CQAs for EM buccal tablets are Mucoadhesive strength, swelling index and drug release (dependent variables); the CMAs identified for EM buccal tablets were Carbopol 934P, HPMC-K100M and chitosan (independent variables). Diluent quantity, blending time and compression force were selected as CPPs; the Box-Behnkentdesign was used to evaluate the relationship between the CMAs and CPPs. Based on the DoE, the composition of the optimised formulation of EM BT-18 consists of 20mg of EM, 15 mg of carbopol 934p, 17 mg of HPMC-K100M, 10mg of chitosan, 30 mg of PVP K-30, 1 mg of magnesium stearate, 16 mg of Mannitol, 1 mg of aspartame, and 50 mg of Ethyl cellulose. The optimised formulation of EM BT 18 was found to have a Mucoadhesive strength of 24.32±0.30g. The swelling index was 90.74±0.25% and drug release was sustained up to 10 hours 98.4±3.62% compared to the marketed product, whose release was up to 8 hours. We attempted to design a buccal tablet of Enalapril Maleate for sustained drug release in the treatment of hypertension. Patients who cannot take oral medication due to trauma or unconscious conditions could receive the formulation. Development of a newly P.ceutical product is very time-consuming, extremely costly and high-risk, with very little chance of a successful outcome. Hence, this study showed EM tablets are already available on the market but we have chosen a buccal drug delivery system using a novel approach using QbD tools to target the quality of the product accurately.

Nanoliposomal Encapsulation of Capparis spinosa Extract and Its Application in Jelly Formulation.

This research aimed to encapsulate the Capparis spinosa fruit extract to increase its stability for incorporation into food products such as jelly or jelly powder. After extraction, the nanoliposomes containing the extract were prepared in ratios of 60-0, 50-10, 40-20, and 30-30 lecithin-to-cholesterol. The effects of lecithin-to-cholesterol concentrations on the related parameters were then evaluated. The results showed that the average particle size was in the range of 95.05 to 164.25 nm, and with an increasing cholesterol concentration, the particle size of the nanoliposomes increased. The addition of cholesterol increased the zeta potential from -60.40 to -68.55 millivolt. Furthermore, cholesterol led to an increase in encapsulation efficiency, and even improved the stability of phenolic compounds loaded in nanoliposomes during storage time. Fourier transform infrared (FTIR) spectroscopy confirmed the successful loading of the extract. Field emission scanning electron microscopy (FE-SEM) analysis revealed nano-sized spherical and almost-elliptical liposomes. For jelly powders, the water solubility index ranged from 39.5 to 43.7% (p > 0.05), and the hygroscopicity values ranged between 1.22 and 9.36 g/100 g (p < 0.05). In conclusion, nanoencapsulated Capparis spinosa extract displayed improved stability and can be used in jelly preparation without any challenge or unfavorable perception.

Antimicrobial and Anesthetic Niosomal Formulations Based on Amino Acid-Derived Surfactants.

BACKGROUND: This work proposes the development of new vesicular systems based on anesthetic compounds (lidocaine (LID) and capsaicin (CA)) and antimicrobial agents (amino acid-based surfactants from phenylalanine), with a focus on physicochemical characterization and the evaluation of antimicrobial and cytotoxic properties. METHOD: Phenylalanine surfactants were characterized via high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Different niosomal systems based on capsaicin, lidocaine, cationic phenylalanine surfactants, and dipalmitoyl phosphatidylcholine (DPPC) were characterized in terms of size, polydispersion index (PI), zeta potential, and encapsulation efficiency using dynamic light scattering (DLS), transmitted light microscopy (TEM), and small-angle X-ray scattering (SAXS). Furthermore, the interaction of the pure compounds used to prepare the niosomal formulations with DPPC monolayers was determined using a Langmuir balance. The antibacterial activity of the vesicular systems and their biocompatibility were evaluated, and molecular docking studies were carried out to obtain information about the mechanism by which these compounds interact with bacteria. RESULTS: The stability and reduced size of the analyzed niosomal formulations demonstrate their potential in pharmaceutical applications. The nanosystems exhibit promising antimicrobial activity, marking a significant advancement in pharmaceutical delivery systems with dual therapeutic properties. The biocompatibility of some formulations underscores their viability. CONCLUSIONS: The proposed niosomal formulations could constitute an important advance in the pharmaceutical field, offering delivery systems for combined therapies thanks to the pharmacological properties of the individual components.

Preparation of Erlotinib hydrochloride nanoparticles (anti-cancer drug) by RESS-C method and investigating the effective parameters.

The size of the drug particles is one of the essential factors for the proper absorption of the drug compared to the dose of the drug. When particle size is decreased, drug uptake into the body increases. Recent studies have revealed that the rapid expansion of supercritical solution with cosolvent plays a significant role in preparing micron and submicron particles. This paper examines the preparation of Erlotinib hydrochloride nanoparticles using a supercritical solution through the cosolvent method for the first time. An examination of the parameters of temperature (318-338 K), pressures (15-25 MPa) and nozzle diameter (300-700 µm) was investigated by Box-Behnken design, and their respective effects on particle size revealed that the nozzle diameter has a more significant impact on particle size than the other parameters. The smallest particles were produced at temperature 338 K, pressure 20 MPa, and nozzle diameter 700 µm. Besides, the ERL nanoparticles were characterized using SEM, DLS, XRD, FTIR, and DSC analyses. Finally, the results showed that the average size of the ERL particles decreased from 31.6 µm to 200-1100 nm.

Potential of Powder Rheology for Detecting Unforeseen Cross-Contamination of Foreign Active Pharmaceutical Ingredients.

Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply of drugs and the safety of customers. In Japan, in 2020, a mix-up containing a sleeping drug went undetected by liquid chromatography during the final quality test because the test focused only on the main active pharmaceutical ingredient (API) and known impurities. In this study, we assessed the ability of a powder rheometer to analyze powder characteristics in detail to determine whether it can detect the influence of foreign APIs on powder flow. Aspirin, which was used as the host API, was combined with the guest APIs (acetaminophen from two manufacturers and albumin tannate) and subsequently subjected to shear and stability tests. The influence of known lubricants (magnesium stearate and leucine) on powder flow was also evaluated for standardized comparison. Using microscopic morphological analysis, the surface of the powder was observed to confirm physical interactions between the host and guest APIs. In most cases, the guest APIs were statistically detected due to characteristics such as their powder diameter, pre-milling, and cohesion properties. Furthermore, we evaluated the flowability of a formulation incorporating guest APIs for direct compression method along with additives such as microcrystalline cellulose, potato starch, and lactose. Even in the presence of several additives, the influence of the added guest APIs was successfully detected. In conclusion, powder rheometry is a promising method for ensuring stable product quality and reducing the risk of unforeseen cross-contamination by foreign APIs.

Croscarmellose Sodium as Pelletization Aid in Extrusion-Spheronization.

Only few excipients are known to be suitable as pelletization aids. In this study, the potential use of croscarmellose sodium (CCS) as pelletization aid was investigated. Furthermore, the impact of cations on extrusion-spheronization (ES) of CCS was studied and different grades of CCS were tested. The influence of different cations on the swelling of CCS was investigated by laser diffraction. Mixtures of CCS with lactose monohydrate as filler with or without the inclusion of different cations were produced. The mixtures were investigated by mixer torque rheometry and consequently extruded and spheronized. Resulting pellets were analyzed by dynamic image analysis. In addition, mixtures of different CCS grades with dibasic calcium phosphate anhydrous (DP) and a mixture with praziquantel (PZQ) as filler were investigated. Calcium and magnesium cations caused a decrease of the swelling of CCS and influenced the use of CCS as pelletization aid since they needed to be included for successful ES. Aluminum, however, led to an aggregation of the CCS particles and to failure of extrusion. The inclusion of cations decreased the uptake of water by the mixtures which also reduced the liquid-to-solid-ratio (L/S) for successful ES. This was shown to be dependent on the amount of divalent cations in the mixture. With DP or PZQ as filler, no addition of cations was necessary for a successful production of pellets, however the optimal L/S for ES was dependent on the CCS grade used. In conclusion, CCS can be used as a pelletization aid.

Oleogels: Versatile Novel Semi-Solid System for Pharmaceuticals.

Oleogels is a novel semi-solid system, focusing on its composition, formulation, characterization, and diverse pharmaceutical applications. Due to their stability, smoothness, and controlled release qualities, oleogels are frequently utilized in food, cosmetics, and medicinal products. Oleogels are meticulously formulated by combining oleogelators like waxes, fatty acids, ethyl cellulose, and phytosterols with edible oils, leading to a nuanced understanding of their impact on rheological characteristics. They can be characterized by methods like visual inspection, texture analysis, rheological measurements, gelation tests, and microscopy. The applications of oleogels are explored in diverse fields such as nutraceuticals, cosmetics, food, lubricants, and pharmaceutics. Oleogels have applications in topical, transdermal, and ocular drug delivery, showcasing their potential for revolutionizing drug administration. This review aims to enhance the understanding of oleogels, contributing to the evolving landscape of pharmaceutical formulations. Oleogels emerge as a versatile and promising solution, offering substantial potential for innovation in drug delivery and formulation practices.

Application of Quality by Design in the Development of Hydrogen Sulfide Donor Loaded Polymeric Microparticles.

Hydrogen sulfide (H2S) is a multifaceted gasotransmitter molecule which has potential applications in many pathological conditions including in lowering intraocular pressure and providing retinal neuroprotection. However, its unique physicochemical properties pose several challenges for developing its efficient and safe delivery method system. This study aims to overcome challenges related to H2S toxicity, gaseous nature, and narrow therapeutic concentrations range by developing polymeric microparticles to sustain the release of H2S for an extended period. Various formulation parameters and their interactions are quantitatively identified using Quality-by-Design (QbD) approach to optimize the microparticle-based H2S donor (HSD) delivery system. Microparticles were prepared using a solvent-evaporation coacervation process by using polycaprolactone (PCL), soy lecithin, dichloromethane, Na2S.9H2O, and silicone oil as polymer, surfactant, solvent, HSD, and dispersion medium, respectively. The microparticles were characterized for size, size distribution, entrapment efficiency, and H2S release profile. A Main Effects Screening (MES) and a Response Surface Design (RSD) model-based Box-Behnken Design (BBD) was developed to establish the relationship between critical process parameters (CPPs) and critical quality attributes (CQAs) qualitatively and quantitatively. The MES model identified polymer to drug ratio and dispersion medium quantity as significant CPPs among others, while the RSD model established their quantitative relationship. Finally, the target product performance was validated by comparing predicted and experimental outcomes. The QbD approach helped in achieving overall desired microparticle characteristics with fewer trials and provided a mathematical relationship between the CPPs and the CQAs useful for further manipulation and optimization of release profile up to at least 30 days.

Physiologically Based Biopharmaceutics Modeling for Gefapixant IR Formulation Development and Defining the Bioequivalence Dissolution Safe Space.

Gefapixant is a weakly basic drug which has been formulated as an immediate release tablet for oral administration. A physiologically based biopharmaceutics model (PBBM) was developed based on gefapixant physicochemical properties and clinical pharmacokinetics to aid formulation selection, bioequivalence safe space assessment and dissolution specification settings. In vitro dissolution profiles of different free base and citrate salt formulations were used as an input to the model. The model was validated against the results of independent studies, which included a bioequivalence and a relative bioavailability study, as well as a human ADME study, all meeting acceptance criteria of prediction errors ≤ 20% for both Cmax and AUC.  PBBM was also applied to evaluate gastric pH-mediated drug-drug-interaction potential with co-administration of a proton pump inhibitor (PPI), omeprazole. Model results showed good agreement with clinical data in which omeprazole lowered gefapixant exposure for the free base formulation but did not significantly alter gefapixant pharmacokinetics for the citrate based commercial drug product. An extended virtual dissolution bioequivalence safe space was established.  Gefapixant drug product batches are anticipated to be bioequivalent with the clinical reference batch when their dissolution is > 80% in 60 minutes. PBBM established a wide dissolution bioequivalence space as part of assuring product quality.

Formulation Development and Evaluation of Cannabidiol Hot-Melt Extruded Solid Self-Emulsifying Drug Delivery System for Oral Applications.

Cannabidiol (CBD) is a highly lipophilic compound with poor oral bioavailability, due to poor aqueous solubility and extensive pre-systemic metabolism. The aim of this study was to explore the potential of employing Hot Melt Extrusion (HME) technology for the continuous production of Self Emulsifying Drug Delivery Systems (SEDDS) to improve the solubility and in vitro dissolution performance of CBD. Accordingly, different placebos were processed through HME in order to obtain a lead CBD loaded solid SEDDS. Two SEDDS were prepared with sesame oil, Poloxamer 188, Gelucire®59/14, PEO N80 and Soluplus®. Moreover, Vitamin E was added as an antioxidant. The SEDDS formulations demonstrated emulsification times of 9.19 and 9.30 min for F1 and F2 respectively. The formed emulsions showed smaller droplet size ranging from 150-400 nm that could improve lymphatic uptake of CBD and reduce first pass metabolism. Both formulations showed significantly faster in vitro dissolution rate (90% for F1 and 83% for F2) compared to 14% for the pure CBD within the first hour, giving an enhanced release profile. The formulations were tested for stability over a 60-day time period at 4°C, 25°C, and 40°C. Formulation F1 was stable over the 60-day time-period at 4°C. Therefore, the continuous HME technology could replace conventional methods for processing SEDDS and improve the oral delivery of CBD for better therapeutic outcomes.

Consensus Statements on the Use of Novel Formulations of Isotretinoin: A Modified Delphi Process.

Oral isotretinoin remains a mainstay of treatment for severe, recalcitrant nodular acne. Novel formulations of isotretinoin have been developed over the past decade, including lidose isotretinoin and micronized isotretinoin. It is important to understand the differences between isotretinoin formulations to help guide clinical decision-making and selection of isotretinoin therapy. This study aims to provide evidence-based consensus statements regarding the use of novel formulations of isotretinoin for the treatment of moderate-to-severe acne. The Expert Consensus Group consisted of dermatologists with expertise in the treatment of acne. Voting members met in person to conduct a modified Delphi process; a maximum of 2 rounds of voting were conducted for each consensus statement. A total of 5 statements were generated regarding the use of novel formulations of isotretinoin, addressing the efficacy, tolerability, and side effects of novel isotretinoin formulations. All 5 statements achieved agreement with high consensus. The Expert Consensus Group agrees that individualized selection of isotretinoin therapy is important to maximize efficacy and minimize side effects. Compared to generic isotretinoin, micronized isotretinoin may require lower doses to achieve sufficient plasma concentrations. With the increased bioavailability of micronized formulation, there is no need to calculate cumulative dose; instead, the general recommendation with micronized isotretinoin is to treat for at least 5 months, or longer if needed to achieve clearance. Micronized isotretinoin can be taken in the fed or fasted state and has an acceptable safety profile. J Drugs Dermatol. 2024;23(6):429-432.     doi:10.36849/JDD.7971.

Encapsulation of three different types of polyphenols in casein using a customized pH-driven method: Preparation and characterization.

Phenolic compounds represent natural compounds endowed with diverse biological functionalities. However, their inherent limitations, characterized by poor water solubility and low oral bioavailability, limit their broader applications. Encapsulation delivery systems are emerging as a remedy, able to ameliorate these limitations by enhancing the stability and solubility of phenolic compounds. In this study, a novel, customized pH-driven approach was developed by determining the optimal deprotonation and protonation points of three different types of polyphenols: ferulic acid, resveratrol, and rhein. The polyphenols were successfully encapsulated in a casein carrier. The solubility, stability, LogD, and LogS curves of the three polyphenols at different pH values were analyzed to identify the optimal deprotonation points for ferulic acid (pH 9), resveratrol (pH 11), and rhein (pH 10). Based on these findings, three different nanoparticles were prepared. The encapsulation efficiencies of the three phenolic compounds were 95.86%, 94.62%, and 94.18%, respectively, and the casein nanoparticles remained stable at room temperature for seven days. FTIR spectroscopy, fluorescence spectroscopy, and molecular docking study substantiated the encapsulation of phenolic compounds within the hydrophobic core of casein-based complexes, facilitated by hydrogen bonding interactions and hydrophobic interactions. Furthermore, the analysis of antioxidant activity elucidated that casein nanoparticles heightened both the water solubility and antioxidant efficacy of the phenolic compounds. This customized encapsulation technique, by establishing a transitional pH value, resolves the challenges of chemical instability and facile degradation of polyphenols under alkaline conditions in the application process of pH-driven methods. It presents novel insights for the application of polyphenols in the domains of food and biomedical fields.