High Drug Content Research Articles

Timolol Maleate Microspheres: An Ingenious Carrier for Sustained Release Antihypertensive Formulation

Background: Timolol maleate is classified as a BCS Class I drug and functions as a non-selective β-adrenergic receptor blocker. Its ability to lower heart rate and cardiac output has led to its widespread use in the treatment of hypertension. Objective: Timolol maleate has a short half-life and is rapidly cleared from the body, which limits its therapeutic effectiveness, requiring frequent dosing and potentially affecting patient adherence. To overcome these challenges, sustained-release microspheres of Timolol maleate were developed using the ion gelation method. Method: The ion gelation technique was employed to create the microspheres due to its various advantages, including ease of use, scalability and gentle processing conditions. Results: All batches exhibited a comparatively lower swelling index in 0.1M HCl (pH 1.2) than in SIF (pH 6.8). It was observed that increasing the concentration of sodium alginate resulted in higher drug content. The microspheres were sized between 400 and 900 μm and demonstrated excellent flow characteristics. An optimized batch achieved an entrapment efficiency of 88.83% and released 92.15% of the drug over 7 hrs. Furthermore, stability studies conducted according to ICH Q1A(R2) for 3 months at 5±3°C and 25±2°C/60±5% RH indicated no significant changes in evaluation parameters. Conclusion: The optimized Timolol maleate-loaded microspheres effectively provided sustained drug release through the membrane over 7 hrs. This study contributes to the development of improved drug delivery systems for better hypertension management, addressing the unmet needs in patient compliance. Keywords: Timolol Maleate, Microspheres, Ion gelation method, Sodium alginate, Calcium chloride, Sustained release, Hypertension

Development and characterization of solriamfetol-loaded PVA/PLGA electrospun nanofiber membranes: A promising approach for sustained narcolepsy treatment

Narcolepsy presents challenges in medication adherence and delivery, with traditional oral medications not always suitable for patients experiencing unexpected sleep episodes or difficulty in swallowing pills. This study focused on developing a solriamfetol (SF) loaded nanofiber membrane using a polymer blend of polyvinyl alcohol (PVA) and polylactic-co-glycolic acid (PLGA) for the management of narcoleptic patients with non-oral dosage options. The design required synthesis, optimization, characterization, and evaluation of these nanofibers for transdermal drug delivery. Using a Box-Behnken design, the nanofibers were produced via the electrospinning technique, achieving a high drug content of 96.31 ± 1.21 % and entrapment efficiency of 96.18 ± 1.42 %. The in vitro drug release studies demonstrated a prolonged release profile of SF over 24 h, with 97 % ± 2 % of the drug released. The SEM analysis revealed that the surface morphology of the nanofibers was smooth and homogenous, and the average diameter of the SF/PVA/PLGA nanofibers was found to be 150.23 ± 2.50 nm. X-ray diffraction results confirmed the amorphous structure of the nanofibers. The zebrafish embryonic toxicological study did not reveal any signs of toxicity or morphological abnormalities in the developing embryos, indicating that the nanofibers are safe. The results point to the applicability of SF nanofiber membranes in personalized narcolepsy therapy, which improves patients’ quality of life and the efficacy of their treatment. These nanofibers can be given in the form of a transdermal patch to patients for sustained drug delivery, even when they fall asleep or when they cannot take medicines orally.

Combined approach of nanoemulgel and microneedle pre-treatment as a topical anticellulite therapy

Background and purpose: Cellulite is caused by changes in the metabolism of the fatty tissue beneath the skin. Methylxanthines and retinoids are commonly added to the different anticellulite products. However, their topical permeation into the dermis is limited. Thus, the objective of this research is to formulate a nanoemulgel (NEG) containing a triple therapy of caffeine, aminophylline, and tretinoin as a topical anticellulite product to improve their skin permeation. Furthermore, the influence of microneedles (MNs) as skin pre-treatment on the permeation of the NEG was investigated. Experimental approach: Various nanoemulsion (NE) formulations were prepared using high-energy ultrasonication with different compositions and sonication amplitudes. Several characterisation tests were employed to select the optimum NE formulation. Then, the optimised NE formulation was incorporated with hyaluronic acid to prepare the NEG, which was, in turn, subjected to various evaluations. An ex vivo permeation study using human skin was performed for the NEG compared to a control preparation of plain gel. Additionally, a microneedling pen was applied as a skin pre-treatment at varying lengths prior to NEG application to examine its impact on the NEG’s permeation. Key results: The selected NEG has a homogenous and consistent texture with no coarse particles, a droplet size of 175.8 nm and polydispersity index (PDI) of 0.19, an optimum pH value of 5.28, high drug content of caffeine, aminophylline, and tretinoin (99.35, 98.48 and 98.05 %, respectively), high drug release values of approximately 100 % within 6 hours, appro-priate viscosity, minimum skin irritation, and adequate short-term stability. The ex vivo permeation study showed that caffeine, aminophylline, and tretinoin permeated more and deposited in the skin with higher percentages from the NEG than plain gel. This skin deposition within the dermis was increased by applying the microneedling pen at varying lengths of 0.5, 1, and 2 mm as a skin pre-treatment. Conclusion: This combined approach of NEG formulation containing a triple therapy of caffeine, aminophylline, and tretinoin, along with MNs application, has the potential to serve as a topical anticellulite product, reducing cellulite formation and improving skin appearance.

Naringenin Nanocrystals Mitigate Rotenone Neurotoxicity in SH-SY5Y Cell Line by Modulating Mitophagy and Oxidative Stress.

Naringenin, a potent antioxidant with anti-apoptotic effects, holds potential in counteracting rotenone-induced neurotoxicity, a model for Parkinson's disease, by reducing oxidative stress and supporting mitochondrial function. Rotenone disrupts ATP production in SH-SY5Y cells through mitochondrial complex-I inhibition, leading to increased reactive oxygen species (ROS) and cellular damage. However, the therapeutic use of naringenin is limited by its poor solubility, low bioavailability, and stability concerns. Nano crystallization of naringenin (NCs), significantly improved its solubility, dissolution rates, and stability for targeted drug delivery. The developed NAR-NC and HSA-NAR-NC formulations exhibit particle sizes of 95.23nm and 147.89nm, with zeta potentials of -20.6mV and -28.5mV, respectively. These nanocrystals also maintain high drug content and show stability over time, confirming their pharmaceutical viability. In studies using the SH-SY5Y cell line, these modified nanocrystals effectively preserved mitochondrial membrane potential, sustained ATP production, and regulated ROS levels, counteracting the neurotoxic effects of rotenone. Naringenin nanocrystals offer a promising solution for improving the stability and bioavailability of naringenin, with potential therapeutic applications in neurodegenerative diseases.

A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale

Poor aqueous solubility of preexisting and emerging drug molecules is a common issue faced in the field of pharmaceutics. To address this, particle size reduction techniques, including drug micro- and nanonisation have been widely employed. Nanocrystals (NCs), drug particles with particle sizes below 1 µm, offer high drug content, improved dissolution, and long-acting capabilities. Media milling is the most used method to prepare NCs using of-the-shelf machinery, both at the laboratory and industrial scales. However, early NCs development, especially when limited amounts of the active are available, require the use of milligram-scale media milling. This study introduces a novel mini-scale milling device (Mini-mill) that incorporates temperature control through a water-cooled jacket. The device was used to produce NCs of three model hydrophobic drugs, itraconazole, ivermectin and curcumin, with lowest particle sizes of 162.5 ± 0.4 nm, 178 ± 2 nm, and 116.7 ± 0.7 nm, respectively. Precise control of milling temperature was achieved at 15, 45, and 75°C, with drug dependent particle size reduction trends, with no adverse effects on the milling materials or polymorphic changes in the NCs, as confirmed by calorimetric analysis. Finally, a scale-up feasibility study was carried out in a lab-scale NanoDisp®, confirming that the novel Mini-mills are a material-efficient tool for early formulation development, with potential for scale-up to commercial mills.

Optimizing the Formula of Polymeric-Based Aripiprazole Nanosuspension Using Response Surface Methodology for Intranasal Drug Delivery

This study aimed to optimize the formula of aripiprazole nanosuspension for intranasal drug delivery. Response Surface Methodology (RSM) was employed to determine the influence of independent variables, including drug concentration, polymer concentration, and the ratio of polymer combination, on the nanosuspension characteristics. The parameters under investigation were particle size (d mean), polydispersity index, and drug content. Fifteen formulas were prepared using the high-shear homogenization–ultrasonication method, and the Design Expert software was applied for optimum formula determination. The result showed significant effects of the independent variables on the nanosuspension characteristics, with particle sizes ranging from 143.6 – 334.6 nm, PDI values of 0.302 – 0.649, and drug content was 98.7 – 102.1 %. The predicted optimum formula had a drug concentration of 28 mg/mL in the organic solvent, polymer concentration of 1.5% (w/v), and HPMC to PVP ratio of 1.4 with desirability of 0.94. Additionally, it exhibited desirable characteristics, such as a particle size of 171.2  11.4 nm, a PDI value of 0.317  0.02, and a high drug content of 100.04  0.65%. In conclusion, the presented methodology appeared to be perfect for the optimization of the aripiprazole nanosuspension formula to ensure suitability for nose-to-brain drug delivery.

Effect of Pluronic F127 Concentration on Gelling Temperature and other Parameters of Lomustine Mucoadhesive In-Situ Gel

Pluronic F127 is one of the widely used thermoreversible gelling agent, and used in sol-to-gel transformation. It has been used to localize drug delivery such as nose-to-brain delivery which allows the direct targeting of drug molecules bypassing the systemic effect and BBB (Blood Brain Barrier). The anticancer drug lomustine had poor oral bioavailability in addition to its serious side effect, therefore, developing more effective drug delivery with direct targeting towards the brain through intra-nasal administration applying nanoemulsion-based-in situ gel technology is a promising alternative. The work involved formulation of lomustine as in situ gel using Pluronic F127 and study the effect of the polymer on solution to gel transition temperature, gelation behaviour, spreadability, mucoadhesive force, residence time and residence drug percentage, as well as in vitro drug release. The results showed acceptable pH and high drug content, beside increased Pluronic percentage (from 15 to 20%) led to reduced gelation temperature from 33°C to 27°C and spreadability, improved gelling properties from + to +++, increasing mucoadhesive force from 4965.33 to 9866.30 dyne/cm2 as well as prolonged residence time from 30 to 66 min and in vitro drug release where was 120 min for 100% drug release from F1 that contained 15% of the polymer to 210 min for F3 with 20% polymer. Therefore, modifying the Pluronic F127 percent in the in situ formulas could optimize the required formula for targeting the anticancer to treat brain cancer via nose-to-brain delivery.

Novel pH-Responsive Structural Rearrangement of Myristic Acid-Conjugated Quetiapine Nanosuspension for Enhanced Long-Acting Delivery Performance.

Quetiapine myristate (QM), an ester-bonded lipophilic prodrug of quetiapine (QTP), is synthesized and converted into an amphiphilic structure in acidic pH to trigger a novel self-assembled QM nanosuspension (QMN). Following injection, this QMN rearranges within physiological pH to form nanoaggregates in structure, resulting in enhanced physicochemical properties and in vivo therapeutic performance without an initial burst release. The 200-nm-sized QMN exhibits less invasive injection, higher drug content, and better storage stability profile than conventional poly(lactide-co-glycolide) (PLGA) nanosuspensions containing QTP or QM. Following a single intramuscular injection to beagle dogs (35mg kg-1 QTP), QMN undergoes pH-responsive nanoaggregation to form the lipophilic prodrug, providing esterase-oriented sustained release for five weeks compared with the two-week period of PLGA nanosuspensions. Notably, QMN exhibits improved in vivo pharmacokinetic performance with long-acting delivery while minimizing issues associated with polymeric PLGA formulations, including the initial massive burst release, cellular toxicity, and adverse side effects. These results support the further development of QMN as a novel long-acting injectable to improve patient compliance and dosing frequency.

A one-dimensional bacterial cellulose nano-whiskers-based binary-drug delivery system for the cancer treatment

It's currently a challenge to design a drug delivery system for chemotherapy with high drug contents and minimal side effects. Herein, we constructed a novel one-dimensional binary-drug delivery system for cancer treatment. In this drug delivery system, drugs (doxorubicin (DOX) and resveratrol (RES)) self-assemble on bacterial cellulose nano-whiskers (BCW) and are subsequently encapsulated by polydopamine (PDA) with high encapsulation efficiencies (DOX: 81.53 %, RES: 70.32 %) and high drug loading efficiencies (DOX: 51.54 %, RES: 36.93 %). The cumulative release efficiencies can reach 89.27 % for DOX and 80.05 % for RES in acidic medium within 96 h. The BCW/(DOX + RES)/PDA can enter tumor cells easily through endocytosis and presents significant anti-cancer effects. Furthermore, the released-RES plays a protective role in normal cells through up-regulation of antioxidant enzymes activities and scavenging of reactive oxygen species. Taken together, the one-dimensional BCW/(DOX + RES)/PDA binary-drug delivery system can be used for the anticancer treatment along with slight side effects.

Regulating Drug Release Performance of Acid-Triggered Dimeric Prodrug-Based Drug Self-Delivery System by Altering Its Aggregation Structure.

Dimeric prodrugs have been investigated intensely as carrier-free drug self-delivery systems (DSDSs) in recent decades, and their stimuli-responsive drug release has usually been controlled by the conjugations between the drug molecules, including the stimuli (pH or redox) and responsive sensitivity. Here, an acid-triggered dimeric prodrug of doxorubicin (DOX) was synthesized by conjugating two DOX molecules with an acid-labile ketal linker. It possessed high drug content near the pure drug, while the premature drug leakage in blood circulation was efficiently suppressed. Furthermore, its aggregation structures were controlled by fabricating nanomedicines via different approaches, such as fast precipitation and slow self-assembly, to regulate the drug release performance. Such findings are expected to enable better anti-tumor efficacy with the desired drug release rate, beyond the molecular structure of the dimeric prodrug.

A Stereolithography-Based Modified Spin-Casting Method for Faster Laboratory-Scale Production of Dexamethasone-Containing Dissolving Microneedle Arrays.

Microneedle arrays (MNAs) consist of a few dozens of submillimeter needles, which tend to penetrate through the stratum corneum layer of the skin and deliver hardly penetrating drugs to the systemic circulation. The application of this smart dosage form shows several advantages, such as simple use and negligible pain caused by needle punctures compared to conventional subcutaneous injections. Dissolving MNAs (DMNAs) represent a promising form of cutaneous drug delivery due to their high drug content, biocompatibility, and ease of use. Although different technologies are suitable to produce microneedle arrays (e.g., micromilling, chemical etching, laser ablation etc.), many of these are expensive or hardly accessible. Following the exponential growth of the 3D-printing industry in the last decade, high-resolution desktop printers became accessible for researchers to easily and cost-effectively design and produce microstructures, including MNAs. In this work, a low force stereolithography (LFS) 3D-printer was used to develop the dimensionally correct MNA masters for the spin-casting method. The present study aimed to develop and characterize drug-loaded DMNAs using a two-level, full factorial design for three factors focusing on the optimization of DMNA production and adequate drug content. For the preparation of DMNAs, carboxymethylcellulose and trehalose were used in certain amounts as matrices for dexamethasone sodium phosphate (DEX). Investigation of the produced DexDMNAs included mechanical analysis via texture analyzer and optical microscopy, determination of drug content and distribution with HPLC and Raman microscopy, dissolution studies via HPLC, and ex vivo qualitative permeation studies by Raman mapping. It can be concluded that a DEX-containing, mechanically stable, biodegradable DexDMNA system was successfully developed in two dosage strengths, of which both efficiently delivered the drug to the lower layers (dermis) of human skin. Moreover, the ex vivo skin penetration results support that the application of DMNAs for cutaneous drug delivery can be more effective than that of a conventional dermal gel.

Unveiling the Preparation and Characterization of Lercanidipine Hydrochloride in an Oral Solid Self-Nanoemulsion for Enhancing Oral Delivery.

Chronic kidney disease (CKD) is becoming increasingly prevalent worldwide, particularly among the elderly, along with an increase in the incidence of hypertension and cardiovascular disorders. Developing lipid-based oral dosage forms with a higher expected bioavailability of antihypertensive drugs with nephroprotective effects poses a challenge. Lercanidipine hydrochloride (LRCH) is a newer type of third-generation dihydropyridine calcium channel blocker that functions as an antihypertensive and has significant nephroprotective effects. Due to its extensive first-pass metabolism, its bioavailability is about 10% and increases to 3-4 times when taken with a high-fat meal. Targeting this drug to the lymphatic system using the solid self-nano-emulsifying drug delivery system (SSNEDDS) is a promising approach for improving LRCH's bioavailability and dispersion rate. SSNEDDS combines the benefits of both liquid self-emulsifying and solid dosage forms, improving drug stability and extending storage time. In this study, liquid SNEDDS composed of 10% peppermint oil, 67% Tween 20, and 22.5% propylene glycolwas solidified using two adsorbent agent mixtures (SSNEDDS1: Avicel PH 101 and Aerosil 200) and (SSNEDDS2: Avicel PH 102 and Aerosil 200) separately. The prepared formulations were evaluated for powder flow, drug content, and an in-vitro dispersion test in comparison to the brand-marketed tablet as a standard or pure drug. DSC and X-ray diffraction analysis were also used. The SSNEDDS2 shows excellent flowability, a higher drug content (99.761%), and a significantly higher and faster dispersion rate of 100% within 10 minutes compared to 92% of the marketed LRCH tablet and 18.1% of the pure drug for 60 minutes. The solid-state characterization of the formulation composed of SSNEDDS2 confirmed that the LRCH was in an amorphous form inside the solidified nano system without interacting with the excipient. This study successfully prepared LRCH using the promising strategy of SSNEDDS as a hard gelatin capsule with a higher dispersion rate. It improved its stability and expected bioavailability compared to the brand-marketed tablet as the standard.

Development of dexibuprofen loaded nano transfersomal gel with enhanced biopharmaceutical performance in complete Freund's adjuvant induced arthritis model

The purpose of this study was to enhance the biopharmaceutical performance of Dexibuprofen (DXI) using transfersomal gel (DXI-TG) as drug delivery system. DXI loaded transfersomes (DXI-T) were prepared via thin film technique, characterized for particle size, polydispersity index, zeta potential, particle morphology and entrapment efficiency. The DXI-T was further incorporated into 2 % (w/v) chitosan gel to get the final dosage form DXI-TG, which was characterized for homogeneity, pH, spread-ability and rheological properties. In vitro release, ex vivo permeation and in vivo studies were also conducted along with stability study of the optimized formulation. DXI-T showed excellent vesicle properties including, size distribution (235.1 ± 4.66 nm), poly dispersity index (0.184 ± 0.001), zeta potential (−10.5 ± 0.23 mV) and entrapment efficiency (82.9 ± 1.07 %). TEM analysis exhibited spherical morphology and uniformly distributed nanoparticles, whereas FTIR showed no bond anomalies. DXI-TG showed suitable gel properties with a viscosity of 11310 ± 20 cP, pH 5.2 ± 0.3, good homogeneity, non-Newtonian flow behavior, good spread-ability (298 ± 7.63 %) and high drug content (97.01 ± 3.1 %). in vitro release studies demonstrated that DXI-TG has significantly controlled the release of DXI when compared with DXI-T, DXI-G and DXI-Suspension at pH 5.5 and 7.4. Similarly, ex vivo permeation analysis showed meaningfully increased permeation of DXI-T followed by DXI-TG when compared with test formulations. Like normal control group, skin irritation studies showed no erythema and edema in DXI-TG treated group. Additionally, DXI-TG demonstrated a significantly enhanced bioavailability (5-fold) when compared with DXI-Suspension and DXI-G. Furthermore, DXI-TG showed significantly enhanced therapeutic effect against acute arthritis model when compared with DXI-Suspension and DXI-G. Besides, no signs of evident toxicity on major body organs was observed in DXI-TG treated animal group. Also, the DXI-TG was found stable for a period of 6 months. It can be concluded that transfersomal gel may be a suitable carrier for DXI with enhanced bioavailability, improved therapeutic efficacy and no evident toxicity as exhibited in this study.

Solubility and Dissolution Rate Enhancement of Aceclofenac by Solid Dispersion Employing Kneading and Solvent Evaporation Techniques

Background: Aceclofenac (ACF) is a non-steroidal anti-inflammatory drug with potent anti-inflammatory and analgesic properties. ACF is belongs to BCS class II which has poor solubility in water (practically insoluble) and high permeability that leads to a low dissolution rate and reduced bioavailability. Objective: to enhance the solubility and dissolution rate of ACF using the solid dispersion method (SD) by two common techniques which were solvent evaporation (SE) and kneading (Kn) by using different carriers Mannitol, PVP k30, Soluplus®, and Urea in both techniques at 1:1 and 1:5 wight ratio. Methods: The effects of type of carrier and preparation method on solubility and dissolution rate of SD were studied. Solid dispersions were characterized for their, percentage yield, drug content, drug solubility and in-vitro dissolution rate in comparison with pure drug. Results: The best formula is obtained by the Kn formula (F16) which was formulated by the use of ACF: Soluplus®: with a weight ratio of 1:5 which gave a high percentage yield (99.5%), high drug content (99.8± 0.003%) and the best solubility enhancement which was 361 folds compared to pure ACF and faster dissolution rate which was 80% in 10 minutes compared to 20% for pure drug. Conclusion: the solubility and in-vitro dissolution rate of ACF was efficiently improved when prepared by SD techniques, utilizing both solvent evaporation and kneading methods. Furthermore, the kneading method was superior to solvent evaporation method due to the greater enhancement of solubility and dissolution rate obtained by all carriers and ratios with higher improvement by 1:5 ratio, and can be considered a successful and efficient strategy for solubility and in-vitro dissolution rate improvement of hydrophobic drugs.

Formulation and Characterization of Isoconazole Loaded Invasomal Gel for Effective Antifungal Activity

The characterization of isoconazole invasomal gel formulations (IG1–IG5) aimed to evaluate their physical attributes, drug content, and drug release kinetics for topical application. All formulations exhibited transparency and smooth texture, indicating uniform drug dispersion. While IG1 had an easily pourable consistency, IG4 displayed very good consistency, suggesting viscosity differences. Despite these variations, all formulations showed good homogeneity and high drug content, with IG4 leading in drug content percentage. Spreadability and viscosity varied among formulations, influencing ease of application and adherence to the skin. Cumulative drug release profiles revealed sustained release over 12 hours, with notable differences in release rates and extents among formulations. IG4 exhibited the most sustained release, aligning with pharmacokinetic requirements for antifungal therapy. Its release profile followed a diffusion-controlled mechanism, with a high cumulative drug release percentage of 98.95 ± 0.32% over 12 hours. Antifungal activity against Candida albicans was comparable to Isoconazole, suggesting IG4’s effectiveness in treating fungal infections. Stability studies confirmed the formulation’s stability under tested conditions, supporting its potential for further development and clinical use.

Transition from dripping mode to jetting mode under passive control with a drainage device

Traditional Chinese medicine is a pivotal industry in China, and the technology for manufacturing high-quality pills is of great interest to numerous sectors. Among various methodologies, the liquid drip method has gained significant attention from the pharmaceutical industry due to its advantages such as high drug content uniformity, low cost, ease of operation, high production efficiency, and extensive adjustment range. However, the occurrence of undesirable satellite droplets during the drip production process remains a persistent issue. These satellite droplets are challenging to collect and their prolonged presence can disrupt the normal functioning of the system. Previous studies have identified two primary modes of droplet formation: dripping mode and jetting mode. Given that droplet formation in dripping mode is more stable and satellite droplets can be effectively suppressed, studying the transition between dripping and jetting modes and improving the uniformity of the generated droplets become crucial. Achieving this transition can be accomplished through both active and passive methods. In view of the limitations of the active methods in actual productions, we explored a passive method of adding a drainage device, which can effectively inhibit satellite droplets.In this experimental and numerical simulation investigation, we successfully induced the dripping-to-jetting transition by incorporating a drainage device into the dropper. Additionally, we examined how modifications to the dropper's structure influenced droplet formation. Results indicated that increasing the length and diameter of the drainage device resulted in higher critical Weber numbers required for the dripping-to-jetting transition. Contrarily, the effect of the Kapitza number on the critical Weber numbers exhibited an opposite trend. The critical Kapitza number without complex droplets was also discussed.

Development of nanobigel system combining apoptosis-inducing daidzein and flaxseed oil for the synergistic treatment of skin cancer

Daidzein (DDZ), an isoflavone containing phytoestrogen, and flaxseed oil (FSO), an omega-3-polyunsaturated fatty acid rich dietary lipid, are known to exert anticancer effects via inducing apoptosis in cancer cells. However, oral administration of DDZ and FSO is associated with biopharmaceutical issues. This study aimed to develop a stable topical bigel (BG) system containing DDZ and FSO to exert synergistic effects in the treatment of skin cancer. High speed homogenization method was used for the preparation of DDZ-loaded bigel (DDZ@BG). In vitro investigations and morphological studies were performed to characterize the developed formulation. MTT cytotoxicity tests were conducted to evaluate the effect of the combination of DDZ and FSO on A431human skin cancer cell lines. To assess the toxicity, skin irritation studies using the Draize test was performed followed by histopathological analysis. The optimized DDZ@BG exhibited uniform texture, nanometric size and high drug content with sustained release profile and improved drug permeation. The MTT cytotoxicity studies revealed an IC50 value of 110.2 μg/mL for the optimized formulation. The developed nanobigel formulation exhibited high potential in the effective topical treatment of skin cancer with improved safety profile.

3D printed dispersible efavirenz tablets: A strategy for nasogastric administration in children

Enteral feeding tubes (EFTs) can be placed in children diagnosed with HIV which need nutritional support due to malnutrition. EFTs are the main route for medication administration in these patients, bringing up concerns about off label use of medicines, dose inaccuracy and tube clogging. Here we report for the first time the use of selective laser sintering (SLS) 3D printing to develop efavirenz (EFZ) dispersible printlets for patients with HIV that require EFT administration. Water soluble polymers Parteck® MXP and Kollidon® VA64 were used to obtain both 500 mg (P500 and K500) and 1000 mg printlets (P1000 and K1000) containing 200 mg of EFZ each. The use of SLS 3D printing obtained porous dosage forms with high drug content (20 % and 40 % w/w) and drug amorphization using both polymers. P500, K500 and K1000 printlets reached disintegration in under 230 s in 20 mL of water (25 ± 1 °C), whilst P1000 only partially disintegrated, possibly due to saturation of the polymer in the medium. As a result, the development of dispersible EFZ printlets using hydrophilic polymers can be explored as a potential strategy for drug delivery through EFTs in paediatrics with HIV, paving the way towards the exploration of more rapidly disintegrating polymers and excipients for SLS 3D printing.

Development and Evaluation of Celecoxib Emulgel by Using Natural Oil.

Emulgel combines the qualities of an emulsion with those of a gel. In order to create an emulgel w/o or o/w, emulsions have to be formulated, which are then combined with a gelling agent, resulting in a dual-control drug release. Celecoxib exhibits analgesic, antipyretic and anti-inflammatory activities and is used to treat osteoarthritis, severe pain, rheumatoid arthritis, and other medical conditions. Celecoxib Emulgel was developed and evaluated by using natural oil and carbopol- 940 as a gelling agent in different concentrations. The screening of various oils, co-surfactants and surfactants was performed to determine the solubility. The essential oils (eucalyptus oil and turpentine oil) were used as penetration modifiers. Studies on compatibility with polymers have been conducted, and the results indicate that there should be no physical or chemical interactions between the polymers and the drug substance. For the preparation of emulgel, various emulsions were prepared with Smix (cosurfactant and surfactant) ratios (1:1, 2:1 and 3:1). The selection of a gelling agent was done by incorporating the selected emulsion system ratio of 1:1 with the combinations of polymers carbapol 940, carbapol 934, and HPMC (0:1:0, 0:0.5:1, 0:0:3, 0.5:0:1, 1:0:0) gel base to make a homogenous emulgel. The emulgel was examined visually to see if it had any phase behaviour, feel, spreadability, and grittiness by applying its thin layer to a slide. Then, all six formulations of emulgel were prepared with the selected gelling agent. All emulgels were evaluated for pH, physical properties (consistency, homogeneity, colour, texture), drug content, spreadability, extrudability, swelling index, viscosity, stability and centrifugation. A Franz diffusion cell and an egg membrane were used to perform in-vitro drug release. Among all prepared formulations, EG1 had a better release, higher viscosity, higher drug content, and a higher swelling index than the others. The formulation EG1 showed higher drug release (91.25%) within 8 hours.

Formulation, in vitro and in vivo evaluation of olanzapine nanoparticles dissolving microneedles for transdermal delivery

Olanzapine (OLZ) is classified as a typical antipsychotic drug utilized for the treatment of schizophrenia. Its oral bioavailability is 60% due to its low solubility and pre-systemic metabolism. Hence, the present work aims to formulate and evaluate OLZ nanoparticles dissolving microneedles (MNs) for transdermal delivery to overcome the problems associated with drug administration orally. OLZ nanoparticles were prepared by the nanoprecipitation method. The optimized OLZ nanoparticle formula was utilized for the fabrication of dissolving MNs by loading OLZ nanodispersion into polydimethylsiloxane (PDMS) micromould cavities, followed by casting the polymeric solution of polyvinylpyrrolidone(PVP-K30) and polyvinyl alcohol (PVA) to form MN matrix. The results revealed that the optimized OLZ nanoparticle formula (NP-5) exhibited particle size 115.76±5.45 nm, entrapment efficiency 78.4±5.46, and zeta potential -19.01±1.6 mV. The results of MNs revealed that MN-4 exhibits a high drug content of 98.52%, and ex vivo permeation through rabbit skin exhibited that MN-4 permeates more effectively than a simple patch by approximately 5.16 fold. In vivo pharmacokinetics study revealed that the area under curve AUC 0-∞ of MN-4 was 6054.56±376 ng. h/ml as compared with AUC0-∞ of marketed OLZ tablet was 3975.77±373 ng. h/ml. It can be concluded that the dissolving MN-4 patch is considered a promising formula to overcome the problems associated with drug administration orally and could improve drug bioavailability, in addition to the ease of administering the medication to schizophrenic patients.