Drug Solution Research Articles

A wearable osmotic microneedle patch provides high-capacity sustained drug delivery in animal models.

The maintenance of stable plasma drug concentrations within a therapeutic window can be critical for drug efficacy. Here, we developed a wearable osmotic microneedle (OMN) patch to support sustained drug dosing for at least 24 hours without the use of electronic components. The OMN patch uses an osmotic pressure driving force to deliver drug solution into the skin through three hollow microneedles with diameters of less than 200 micrometers. The rate of drug release was related to the composition and concentration of the osmogen and drug and to the physical properties of the semipermeable membrane separating the low- and high-solute compartments. The OMN patch released the peptide drug exenatide in rats and mice for 24 hours, whereas subcutaneous injection resulted in a burst release and rapid decline in the plasma drug concentration. OMN release of exenatide improved glycemic control in a diabetic mouse model consistent with a sustained effective plasma concentration of the drug. Continuous release of the small-molecule chemotherapeutic drug cytarabine reduced the progression of acute myeloid leukemia in mice more effectively than subcutaneous injection. Further evaluation of the OMN patch in canines demonstrated continuous dosing of cytarabine up to 225 milligrams for 24 hours, satisfying clinical requirements (150 to 300 milligrams daily). OMN patches were well tolerated in human participants with minimal pain or irritation of the skin and a stated preference over other administration routes. This wearable drug delivery system could provide a platform for stable high-dose drug release with convenience and safety.

Physicochemical Exploration of Some Biologically Potent Molecules Prevailing in Aqueous Solution of an Anticoagulant Drug with the Manifestation of Solvation Consequences

Aims: Our research aims to uncover how solute-solvent and solute-solute interactions behave in aqueous solutions, exploring how temperature variations and concentration changes influence these interactions. This can provide deeper insights into the behavior of molecules in different environments, potentially leading to applications in fields such as drug delivery, chemical reactions, and material science. Background: In the aqueous ternary system, the physicochemical interactions between a medically powerful pharmacological molecule and two naturally occurring amino acids were explored. The investigations were performed in a dilute to infinite dilute medium to study the interactions between the solutes and solvent extensively. Objective: The objective of this research is to systematically investigate the nature of solute- solvent and solute-solute interactions in aqueous solutions across a range of temperatures and concentrations. By doing so, we aim to elucidate the underlying principles governing these interactions, which could contribute to a deeper understanding of solution chemistry. This knowledge is intended to inform the development of more efficient and effective applications in various scientific and industrial fields, including drug formulation, catalysis, and material design. Method: To characterize and calculate the interactions in the ternary system, various models and formulas were considered and applied. Based on various parameters, including viscosity B-coefficient, apparent molar volume, and molar conductance from viscosity, density, and conductance studies, varying temperatures and concentrations were used to elucidate the molecular interactions. To elucidate the interactions between solute with co-solute and with solvent, the limiting apparent molar volumes and the experimental slopes, derived from the Masson equation, and the Viscosity constants A and B, obtained via the Jones-Doles equation, were examined. To illustrate the structure- breaking/ making character of the solutes in the solution, Hepler’s method and dB/dT values were applied. Results: The results indicated that hydrophobic-hydrophobic interaction plays a significant role in the system. Conclusion: These amino acid interaction models may explain the properties of a variety of physiologically active compounds, and the mechanism can be expanded to comprehend the nature of similar systems. Furthermore, the research could lead to advancements in areas such as pharmaceutical sciences, where controlling solute interactions is crucial for drug delivery systems, and in environmental chemistry, where understanding pollutant behavior in water is essential for remediation efforts.

Exploration of the Topical Nanoemulgel Bearing with Ferulic Acid and Essential Oil for Diabetic Wound Healing

Aim: To investigate the anti-inflammatory, antioxidant, and diabetic wound healing properties of the novel topical formulation [Ferulic acid-loaded nanoemulgel (DLMGO-G)]. Methods: Ferulic acid nanoemulsion developed with lemongrass oil is investigated in diabetic wound healing. Further nanoemulsion is incorporated into 1% carbopol® 934 to obtain the DLMGO-G. Nanoemulsion was characterized for particle size, and polydispersity index (PDI) was obtained by Malvern Zetasizer (Zetasizer Nano ZS, Malvern, AL, USA), and morphology by TEM (JEM 1400, JOEL, Akishima, Japan). Furthermore, in vitro cell line and in vivo studies were carried out. Results: The developed nanoemulsion showed a globule size of 28.04 ± 0.23 nm and PDI of 0.07 ± 0.01. The morphology of nanoformulations by TEM confirmed the spherical and uniform nature. Further, the nanoformulation in in vitro cell line experiments revealed that the IC50 value was increased by 1.52 times compared to the drug solution. The treatment groups have shown that fibroblast morphologies were spindle-shaped, suggesting that nanoformulation was compatible with the cells and developed normally on nanoformulation. It also reduced ROS with improved internalization more than the control group. The in vitro wound healing model also revealed that nanoformulation had better wound healing activity. In the in vivo diabetic wound studies on male SD rats, the levels of inflammatory markers such as TNF-α, IL-6, IL-22, and IL-1β declined significantly when treated with DLMGO-G. IL-10 levels significantly increased compared to the diseased group, and MMP-9 levels were remarkably decreased compared to the diseased group. Furthermore, histopathological studies showed the regeneration and granulation of tissues. Conclusions: Thus, these findings indicate that FA-loaded nanoemulgel greatly accelerates the healing of wounds in diabetic rats.

Effect of Process Parameters on Nano-Microparticle Formation During Supercritical Antisolvent Process Using Mixed Solvent: Application for Enhanced Dissolution and Oral Bioavailability of Telmisartan Through Particle-Size Control Based on Experimental Design

Background/Objectives: This study investigates the impact of supercritical antisolvent (SAS) process parameters on the particle formation of telmisartan, a poorly water-soluble drug. Methods: A fractional factorial design was employed to examine the influence of the SAS process parameters, including solvent ratio, drug solution concentration, temperature, pressure, injection rate of drug solution, and CO₂ flow rate, on particle formation. Solid-state characterizations of the SAS process particles using XRD and FT-IR confirmed their amorphous nature. The effect of particle size on the kinetic solubility, dissolution, and oral bioavailability of telmisartan was also assessed. Results: Using a mixture of dichloromethane and methanol, telmisartan amorphous nano-microparticles with sizes between 200 and 2000 nm were produced. The key parameters, particularly drug solution concentration and temperature, significantly affected the particle size. Interestingly, the ratio of the solvent mixture also had a significant effect on the particle morphology. Further experiments were performed to determine the conditions for preparing telmisartan amorphous nano-microparticles with various sizes by controlling the solvent mixture ratio and the concentration of the drug solution. It was revealed that a reduction in the amorphous particle size enhanced both the kinetic solubility and dissolution rates, leading to a significantly increased in vivo oral bioavailability in rats compared to unprocessed telmisartan. Conclusions: These findings suggest that SAS processing, utilizing adjustments of process parameters, offers an effective strategy for enhancing the bioavailability of poorly soluble drugs by generating amorphous spherical nano-microparticles with optimized particle size.

Bilosomes and Niosomes for Enhanced Intestinal Absorption and In Vivo Efficacy of Cytarabine in Treatment of Acute Myeloid Leukemia

Cytarabine (CTR) is a hydrophilic anticancer drug used to treat leukemia. It suffers from poor permeability and intestinal metabolism, diminishing its oral bioavailability. Background/Objectives: The objective was to develop and evaluate niosomes and bilosomes for enhanced intestinal absorption; hence, oral bioavailability. Results: CTR-loaded niosomes and bilosomes with vesicle sizes of 152 and 204.3 nm were successfully prepared with acceptable properties. The presence of bile salts increased the zeta potential of bilosomes. The recorded entrapment efficiency of cytarabine was acceptable for such a hydrophilic drug. CTR-bilosomes showed a pH-dependent drug release pattern with preferred release in pH 6.8. Intestinal absorption behavior indicated a site-dependent CTR absorption pattern with unfavorable absorption in the distal intestine. Niosomal and bilosomal formulations enhanced intestinal absorption parameters with evidence for a predominant paracellular absorption mechanism that bypasses intestinal barriers. The investigation of the anti-leukemic effect of niosomal and bilosomal formulations indicated that both formulations ameliorated the blood parameters, reflecting significant improvement in leukemia treatment compared with the drug solution. Pathological examination of blood films revealed decreased blast cells in peripheral blood in groups treated with tested formulations. Methods: Tested formulations were prepared according to the pro-concentrate method and characterized for particle size, zeta potential, entrapment efficiency, and in vitro release. CTR-loaded niosomes and bilosomes were evaluated for enhanced intestinal absorption utilizing the single-pass in situ intestinal perfusion method in rabbits, and the anti-leukemic effect was assessed using the benzene-induced leukemia model in rats. Conclusions: This study introduced surfactant vesicles for enhanced oral bioavailability of CTR.

Thymoquinone loaded nanoemulgel in streptozotocin induced diabetic wound.

Aim: To treat diabetic wound healing with a novel Thymoquinone (TQ) loaded nanoformulation by using combination of essentials oils.Methods: TQ nanoemulsion (NE) was developed with seabuckthorn & lavender essential oils by phase inversion method and mixture design. Further, DIAGEL is obtained by incorporating NE into 1% carbopol®934. Furthermore, particle size, polydispersity index, thermodynamic stability studies, rheology, spreadability, drug content, in-vitro drug release, ex-vivo permeation, anti-oxidant assay, antimicrobial studies, angioirritance, HAT-CAM assay, in-vitro and in-vivo studies were determined.Results: NE has a particle size of 17.79±0.61nm, 0.206±0.012 PDI & found to be thermodynamically stable. DIAGEL exhibited pseudoplastic behavior, sustained drug release, better permeation of TQ and a drug content of 98.54±0.08%. DIAGEL stored for 6months at room temperature and 2-8°C showed no degradation. Further, an improved angiogenesis, absence of angio-irritancy, remarkable antioxidant and antimicrobial activities against Candida albicans & S. aureus were observed. Cytotoxicity analysis revealed nearly 2.28 -folds higherIC50 value than drug solution. Furthermore, inflammatory mediators were reduced in DIAGEL treated animal groups. The histopathological studies confirmed skin healing with regeneration and granulation of tissue.Conclusion: The novel formulation has strong anti-inflammatory, angiogenesis, antioxidant and appreciable diabetic wound healing properties.

Exploring different interactions of biologically potent molecules L-aspartic acid and L-glutamic acid prevailing in aqueous antibiotic compound doxycycline hyclate by experimental and theoretical studies at various temperatures

The present work is a comparative study of interactions between two non-essential amino acids namely L-aspartic acid (L-Asp) and L-glutamic acid (L-Glu) with the aqueous solution of an antibiotic drug, Doxycycline Hyclate (DH) at four distinct temperatures, spaced ten degrees apart, from 288.15 K to 318.15 K and at 1.013 bar atmospheric pressure. The density and viscosity data obtained through experimentation have been implemented to various ascertain densimetric and viscometric characteristics, including the ‘apparent molar volumes’ (ϕv),‘partial molar volumes at infinite dilution’ (ϕv0), ‘limiting apparent molar expansibilities’ (ϕE0), transfer properties (Δtrφv0), interaction parameters (VAB,VABB), heat capacity (Cp), ‘isobaric thermal expansion coefficient’ (α), viscosity B-coefficients, and thermodynamic parameters (Δμ10≠, Δμ20≠, TΔS20≠ and ΔH20≠) of viscous flow.A conductivity study and measurement of surface tension were also performed to find out the molecular interactions. Calculation of dBdT values and Hepler’s constant i.e. ∂2ϕv0∂T2 helped to identify the structure breaking or making behavior of the solution. In addition to that, spectroscopic studies i.e. UV–visible spectra, and 1H NMR support the conclusion about the interactions occurring in the solution. All these experimental and theoretical observations clearly show that interactions of amino acids with the drug molecules are predominant rather than the solute molecules themselves for both the systems and it is higher for the (DH + H2O + Glu) ternary system which is supported by thermodynamic data (ΔG). DFT analysis makes a good agreement with the experimental findings.

FORMULATION AND CHARACTERISATION OF RISEDRONATE SODIUM SUBLINGUAL SPRAY

Objective: To formulate a propellant-free sublingual spray of Risedronate sodium, addressing issues of gastrointestinal side effects associated with current oral formulations and improving patient compliance. Methods: Initially, a fractional factorial design was used to screen variables, followed by a face-centered central composite design for optimization. Formulation batches were characterized by spray pattern, spray angle, leak test, prime test, drug delivery uniformity, drug content per spray, and ex-vivo permeation study. Results: The optimized batch O1 exhibited an ovality ratio of 1.1, a spray angle of 640, and a drug permeation percentage of 4. In vivo absorption analysis revealed that the relative bioavailability of optimized batch O1 was 2.27 times higher than that of the plain drug solution. Compatibility of the product pack with excipients and the drug was confirmed through stability studies of batch O1. Conclusion: The study concluded that Risedronate sodium sublingual spray presents a promising alternative to oral administration, potentially reducing gastrointestinal side effects and enhancing patient compliance.

Physico-Chemical Characterizations of Composited Calcium-Ortho-Phosphate Porous Particles and Their Controlled Release Behavior of Clindamycin Phosphate and Amikacin Sulfate.

The porous particles prepared from composited calcium-ortho-phosphate (biphasic), Thai silk fibroin, gelatin, and alginate, with an organic to inorganic component ratio of 15.5:84.5, were tested for their abilities to control the release of the commercialized antibiotic solutions, clindamycin phosphate (CDP) and amikacin sulfate (AMK). The in vitro biodegradability tests complying to the ISO 10993-13:2010 standard showed that the particles degraded <20 wt% within 56 days. The drugs were loaded through a simple adsorption, with the maximum loading of injection-graded drug solution of 43.41 wt% for CDP, and 39.08 wt% for AMK. The release profiles from dissolution tests of the drug-loaded particles varied based on the adsorption methods used. The drug-loaded particles (without a drying step) released the drug immediately, while the drying process after the drug loading resulted in the sustained-release capability of the particles. The model-fitting of drug release profiles showed the release driven by diffusion with the first-ordered kinetic after the initial burst release. The released CDF and AMK from particles could sustain the inhibition of Gram-positive bacteria and Gram-negative bacteria, respectively, for at least 72 h. These results indicated the potential of these composited particles as controlled-release carriers for CDP and AMK.

Citicoline eluting hydrogels for therapeutic contact lenses intended to treat neurodegenerative diabetic ocular diseases

Ophthalmic neurodegenerative diseases related to diabetes, such as glaucoma and retinopathy, are among the major causes of blindness in the world. Citicoline (CIT) in the form of eye drops is currently used for the treatment/prevention of these diseases, which affect the posterior segment of the eye. To ensure the drug penetration into the back of the eye, frequent instillations of highly concentrated drug solutions are required with potential side effects. Drug-loaded soft contact lenses (SCLs) may be an effective alternative to the conventional eye drop treatment, since they may enable a sustained drug release during daily wear, ensuring a higher drug bioavailability, and avoiding drug waste. In this work, one 2-hydroxyethyl methacrylate (HEMA) based hydrogel was functionalised with N-(3-aminopropyl) methacrylamide hydrochloride (APMA), molecularly imprinted with CIT and loaded with the same drug. The material was extensively characterised, in terms of morphology, optical, mechanical, and physical–chemical properties, namely, equilibrium water content, wettability, oxygen and ionic permeability, Young’s modulus, shear deformation, transmittance and refractive index, before and after steam sterilisation. Additionally, the tendency of the material to adsorb proteins of the lachrymal fluid was evaluated and its biocompatibility was assessed by irritation and cytotoxicity assays. Comparison with the non-functionalised and non-imprinted hydrogel showed that the modified hydrogel led to a sustained in vitro release of a much higher amount of CIT than the original one, while keeping typical values for physical–chemical properties of SCLs. The drug-loaded material resisted steam sterilisation and proved to be biocompatible, demonstrating adequate properties to be used in therapeutic SCLs for the prophylaxis/treatment of neurodegenerative diabetic ocular diseases. The neuroprotective effect of the released drug was confirmed with tests using porcine retinal explants.

Impact of surfactants on solution behavior and membrane transport of amorphous solid dispersions

The purpose of the study was to develop an amorphous solid dispersion (ASD) of a poorly soluble compound (AK100) and investigate the impact of different surfactants on its dissolution, supersaturation and membrane transport. The solubility of the AK100 was determined in crystalline and amorphous form in the absence and presence of three surfactants at different concentrations: sodium dodecyl sulphate (SDS), polysorbate 80 (PS80) and D-α-tocopherol polyethylene glycol succinate (TPGS). The relation between solubility and surfactant solubilization was evaluated using a computational model. The ASD powder was prepared by solvent evaporation for non-sink dissolution experiments with and without the pre-dissolved surfactants. A transport study with Caco-2 cells was conducted to evaluate the impact of surfactants-based formulation on membrane transport. Both the corresponding crystalline and amorphous solubility of AK100 increased linearly as a function of the surfactant concentrations. The supersaturation was maintained for at least three hours in absence of surfactant and in presence of TPGS, whereas supersaturation declined with SDS and PS80. As expected, the membrane flux of the AK100 was higher for the ASD than for the crystalline powder, and further increased with increased concentration of TPGS. The supersaturation ratio based on the activity-based calculation from Caco-2 cells study was always higher than that of the concentration-based one for the amorphous and crystalline forms of AK100. This study shows how additional solubilizing excipients during formulation development can improve the resulting dissolution and phase behavior of supersaturated drug solution.

Bone Healing via Carvacrol and Curcumin Nanoparticle on 3D Printed Scaffolds.

Carvacrol is a potent antimicrobial and anti-inflammatory agent, while curcumin possesses antioxidant, anti-inflammatory, and anticancer properties. These phytochemicals have poor solubility, bioavailability, and stability in their free form. Nanoencapsulation can reduce these limitations with enhanced translational capability. Integrating nanocarriers with 3D-printedcalcium phosphate (CaP)scaffolds presents a novel strategy for bone regeneration. Carvacrol and curcumin-loaded nanoparticles (CC-NP) synthesized with melt emulsification produced negatively charged, monodispersed particles with a hydrodynamic diameter of ≈127nm. Their release from the scaffold shows a biphasic release under physiological and acidic conditions. At pH 5.0, the CC-NP exhibits a 53% release of curcumin and nearly 100% release of carvacrol, compared to 19% and 36% from their respective drug solutions. At pH 7.4, ≈40% of curcumin and 76% of carvacrol releases, highlighting their pH-sensitive release mechanism. In vitro studies demonstrate a 1.4-fold increase in osteoblast cell viability with CC-NP treatment. CC-NP exhibit cytotoxic effects against osteosarcoma cells, reducing cell viability by ≈2.9-fold. The antibacterial efficacy of CC-NP evaluated against Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) exhibiting 98% antibacterial efficacy. This approach enhances therapeutic outcomes and minimizes the potential side effects associated with conventional treatments, paving the way for innovative applications in regenerative medicine.

Recent Advances in the Drugs and Glucose-Responsive Drug Delivery Systems for the Treatment of Diabetes: A Systematic Review.

Diabetes is a common chronic metabolic disease. Different types of drugs play important roles in controlling diabetes and its complications, but there are some limitations. The glucose-responsive drug delivery system is a novel technology with potential in diabetes treatment. It could automatically release drugs in response to changes in glucose levels in the body to maintain blood glucose within a normal range. The emergence of a glucose-sensitive drug delivery system provides a more intelligent and precise way to treat diabetes. The review is carried out according to the Preferred Reporting Items for Systematic Reviews (PRISMA 2020) guidelines This review focuses on the recent advances in the drugs and different systems of glucose-sensitive drug delivery, including glucose oxidase, phenylboronic acid, Concanavalin A, and other glucose-reactive systems. Furthermore, the glucose-responsive drug delivery system combined with the application applied in hydrogels, microneedles, and nanoparticles is also explored and summarized. The new platforms to sustain the release of anti-diabetic drugs could be desirable for patients. It could lead to increased adherence and glycemic outcomes for the detection and treatment of diabetes. Furthermore, given the limitations of glucose-responsive drug delivery systems, solutions and perspectives are proposed to help the understanding and application of these systems. This review will be helpful for drug discovery and treatment of diabetes from a new perspective.

Ocular mucoadhesive and biodegradable spanlastics loaded cationic spongy insert for enhancing and sustaining the anti-inflammatory effect of prednisolone Na phosphate; Preparation, I-optimal optimization, and In-vivo evaluation

This study aimed to formulate and statistically optimize spanlastics loaded spongy insert (SPLs-SI) of prednisolone Na phosphate (PRED) to enhance and sustain its anti-inflammatory effect in a controlled manner. An I-optimal optimization was employed using Design-Expert® software. The formulation variables were sonication time, the Span 60: EA ratio and type of edge activator (Tween 80 or PVA) while Entrapment efficiency (EE%), Vesicles' size (VS) and Zeta potential (ZP) were set as the dependent responses. This resulted in an optimum spanlastics (SPLs) formulation with a desirability of 0.919. It had a Span60:Tween80 ratio of 6:1 with a sonication time of 9.5 min. It was evaluated in terms of its EE%, VS, ZP, release behavior in comparison to drug solution in addition to the effect of aging on its characteristics. It had EE% of 87.56, VS of 152.2 nm and ZP of −37.38 Mv. It showed sustained release behavior of PRED in comparison to drug solution with good stability for thirty days. TEM images of the optimized PRED SPLs formulation showed spherical non-aggregated nanovesicles. Then it was loaded into chitosan spongy insert and evaluated in terms of its visual appearance, pH and mucoadhesion properties. It showed good mucoadhesive properties and pH in the safe ocular region. The FTIR, DSC and XRD spectra showed that PRED was successfully entrapped inside the SPLs vesicles. It was then exposed to an in-vivo studies where it was capable of enhancing the anti-inflammatory effect of PRED in a sustained manner with once daily application compared to commercial PRED solution. The spongy insert has the potential to be a promising carrier for the ocular delivery of PRED.

Biocompatible cationic 5-fluorouracil loaded elastic liposomes for ocular delivery: In vitro, ex vivo, and in vivo evaluation

5-fluorouracil (5-FU) is used to treat scleral and episcleral fibroblast proliferations (scarring process) in the eyes. Frequent washing of the conventional solution results in limited drug access to the eyes. Taguchi and central composite design (CCD) oriented optimized mucoadhesive cationic elastic liposomes were prepared and characterized. The optimized F-CEL8 (composed of 85 mg of dipalmitoyl-phosphatidylcholine, 15 mg of sodium cholate, 10 mg of 5-FU, 7 mg of ethanol, and 883 mg of buffer) and its gel were studied for in vitro and ex vivo drug release profiles as compared to the drug solution and the liposomes. In vitro hemolysis and Draize studies corroborated safety concerns. An in vivo pharmacokinetics study was studied in rats. Each mL of F-CEL8 contained dipalmitoyl-phosphatidylcholine (X1), sodium cholate, and ethanol to deliver 10 mg of 5-FU with optimal vesicle size, low polydispersity index (PDI), and high zeta potential (ZP). The %EE value of spherical F-CEL8 was quite high (82.3 ± 7.1 %) as compared to liposomes (∼53 %) due to the large volume of the inner aqueous chamber of vesicles. F-CEL8-gel exhibited relatively high viscosity for slow and sustained release for 24 h as compared to others. The percent permeation of 5-FU from the solution, F-CEL8, F-CEL8-gel, and the liposomes were found to be 28.6 ± 4.6 %, 69.6 ± 7.4 %, 76.89 ± 12.4 %, and 54.8 ± 5.3 %, respectively. All isotonic formulations did not exhibit hemolysis and irritation to the eyes. The gel illustrated the highest values of pharmacokinetics parameters as compared to the solution and the liposomes, which may be attributed to the maximum residence time achieved through electrostatic interaction (the vesicle internalization with the mucosal layer of eyes).

Relieving postherpetic neuralgia pain via gabapentin-loaded bigels as an auspicious topical drug delivery system.

Over the past decades, a substantial portion of the population worldwide has been infected with varicella zoster and most cases developed shingles. Unfortunately, shingles is usually accompanied by postherpetic neuralgia, which may persist for months to years after the resolution of the viral infection. Gabapentin is an orallygamma-aminobutyric acid analogue approved by the Food and Drug Administration to manage shingles postherpetic neuralgia. However, gabapentin shows nonlinear pharmacokinetics, with variable absorption and bioavailability along with its short half-life and long side effects that may include dizziness and somnolence, which calls for an appropriate topical dosage form. Bigels are unique semisolid dosage forms with boosted penetrability and satisfactory hydrophilic texture. The current work pointed to formulating gabapentin-loaded bigels for the treatment of postherpetic neuralgia, where the analysis and optimization of design were performed via Design-Expert®. The selected bigel (F5), incorporating 400mg Span 60, 1000mg Tween 80, and 1000mg Transcutol, displayed spherical nanosized particles with acceptable viscosity and spreadability. Subsequent topical application of the selected bigel on the skin of Wistar rats, F5, demonstrated a boosted accumulation of gabapentin in the skin similar to PLO gel but superior to the drug solution. Furthermore, a histopathological study demonstrated the biosafety of the selected bigel when applied topically. Accordingly, gabapentin-loaded bigel would be considered a potentially topical dosage form for the delivery of gabapentin for the management of postherpetic neuralgia.

Rosuvastatin Flexible Chitosomes: Development, In Vitro Evaluation and Enhancement of Anticancer Efficacy Against HepG2 and MCF7 Cell Lines.

Rosuvastatin (ROS), a statin drug with promising anticancer properties has a low bioavailability of approximately 20% due to lipophilicity and first-pass metabolism. This study aimed to enhance ROS anticancer efficacy through loading into flexible chitosomes. The chitosomes were prepared starting from negatively charged liposomes through electrostatic interactions with chitosan. The conversion of zeta potential from negative to positive confirmed the successful formation of chitosomes. The chitosan coating increased the particle size and zeta potential, which ranged from 202.0 ± 1.7nm to 504.7 ± 25.0nm and from - 44.9 ± 3.0 mV to 50.1 ± 2.6 mV, respectively. Chitosan and drug concentrations had an important influence on the chitosome properties. The optimum chitosome formulation was used to prepare ROS-loaded flexible chitosomes using different concentrations of four edge activators. The type and concentration of edge activator influenced the particle size, drug entrapment efficiency, and drug release rate of the flexible chitosomes. Flexible chitosomes significantly increased drug permeation through rat abdominal skin compared to control transferosomes and drug solution. The optimal ROS flexible chitosomes containing sodium deoxycholate as an edge activator had a 2.23-fold increase in ROS cytotoxic efficacy against MCF7 cells and a 1.84-fold increase against HepG2 cells. These results underscore the potential of flexible chitosomes for enhancing ROS anticancer efficacy.

Mass balance analysis for therapeutic peptides: Case studies, applications, and perspectives

The concept of mass balance is discussed as it pertains to the pharmaceutical development of therapeutic peptides. Case studies are presented demonstrating how to perform a mass balance assessment on solid drug substance and solution drug product, and the role of mass balance in the context of the overall product control strategy is discussed. Utilizing mass balance as a specification test where the result is calculated from other critical quality attribute tests, each with their own specification, offers little value as a formalized quality acceptance criterion and may create more deviations, non-value added investigations, and potential batch failures. While useful in characterizing the performance of analytical methods and as part of a rigorous understanding of the manufacturing process and control strategy development, mass balance should not be required as a specification control and should instead be demonstrated during method development and through well-designed forced degradation experiments. Analytical method variability is discussed in relation to the analytical target profile, and the overall impact of sources of variability on the mass balance calculation is described in support of this position.

Characterization of macrocyclic peptide drug interactions with bile salts and biorelevant colloids via single amino acid mutations and 1H nuclear magnetic resonance (NMR) spectroscopy

There is growing interest in the oral delivery of poorly permeable peptide drugs; however, the effect of biorelevant colloids found in the aqueous gastrointestinal environment on peptide drug solution behavior has been largely understudied. In this work, we detail the molecular level interactions between octreotide, a water-soluble macrocyclic peptide drug, and biorelevant colloids, i.e. bile salt micelles and bile salt-phospholipid mixed micelles, via dialysis membrane flux experiments and proton nuclear magnetic resonance (1H NMR) spectroscopy. A modified alanine scan was employed to generate eight mutated octreotide analogs; the impact of individual amino acid mutations on peptide dialysis membrane flux rates in micellar (trihydroxy and dihydroxy) bile salt solutions as well as fasted state simulated intestinal fluid (FaSSIF) and fed state simulated intestinal fluid (FeSSIF) was evaluated and compared against the parent peptide, octreotide. We show that octreotide interacts more strongly with dihydroxy bile salt micelles than trihydroxy bile salt micelles in solution, and in FaSSIF/FeSSIF media, octreotide mainly interacts with the phospholipid component. These interactions are largely mediated by hydrophobic interactions of octreotide's aromatic residues as well as electrostatic interactions between octreotide's basic Lys residue and terminal amine.

REVIEW ARTIKEL: PENINGKATAN KELARUTAN SENYAWA OBAT ANTIMALARIA MENGGUNAKAN METODE MODIFIKASI KO-KRISTAL

Malaria is an infectious disease caused by the Plasmodium parasite that infects humans through the bite of female Anopheles mosquitoes. Most antimalarial drugs have limitations in terms of solubility. Drug solubility is a very important parameter that determines the effectiveness of the drug, with good drug solubility, the drug can achieve optimal bioavailability and pharmacological effects, based on this, efforts are needed to overcome these problems in order to provide effective and efficient therapy to patients using existing antimalarial drugs that have been modified in their physicochemical properties so that their solubility increases. The purpose of this study was to review various studies that used the co-crystal modification method to increase the solubility of antimalarial drug compounds. This study was designed using the Narrative Review method, article searches were carried out using two databases, namely Google Scholar and PubMed, with the keywords "Co-crystal" OR "Antimalaria". In this study, 7 articles were found that met the inclusion and exclusion criteria. The selected articles are articles that discuss antimalarial drugs (artesunate, artemisinin, pyrimethamine) developed by the co-crystal method which experienced a multi-fold increase in solubility compared to its pure preparation. The co-crystal method can be a solubility enhancing solution for antimalarial drugs that have low solubility in water, increasing the solubility of antimalarial drugs causes the bioavailability of the drug to increase, so that the drug can provide good therapeutic effects.