Stable Formulation Research Articles

Recent advances on two-dimensional material-based nanosystems for gene delivery

Gene therapy has been extensively investigated and widely used in biomedical fields, such as cancer treatment. However, the most important issues for gene therapy are stability, targeting effect, transfection efficacy, and safety of gene formulation after administration, which seriously limit the further application of gene therapy in clinic. Therefore, gene delivery could be a promising strategy for overcoming these challenges. Two-dimensional (2D) materials are rising nanomaterials with excellent physical and chemical properties, including large specific surface area, easy modification, high conversion efficiency of light, and good biocompatibility, which have achieved promising applications as vehicles for gene delivery in the disease treatment. In this review, we first summarized the research progress of 2D material-based nanosystems for gene delivery to improve the therapeutic efficacy. We discussed that 2D material-based gene delivery nanosystems showed high therapeutic efficacy for many diseases treatment, especially cancer. Furthermore, we also proposed that surface modification of 2D materials might be a promising strategy to prepare multi-functional gene carriers for combination therapy with enhanced treatment efficacy. Finally, the future research progress, challenges, and prospects of 2D material-based nanosystems for gene therapy were discussed and concluded. Conclusively, we believe that 2D material-based nanosystems with good biocompatibility and high transfection efficiency would be potentially used in clinical settings to improve the therapeutic efficacy of gene therapy.

Nanostructured lipid carriers loaded with essential oils: a strategy against SARS-CoV-2

This work aimed to investigate the effectiveness of Lippia sidoides and Syzygium aromaticum essential oils (EOs) encapsulated in nanostructured lipid carriers (NLCs) as SARS-CoV-2 inhibitors through virucidal activity assessment. We developed anionic and cationic NLCs loaded with the EOs and assessed their physicochemical properties and SARS-CoV-2 virucidal activity, focusing on the effects of EO type and the NLCs composition. The NLCs exhibited particle sizes of 141.30 to 160.53 nm for anionic and 109.30 to 138.60 nm for cationic types, with PDIs between 0.16 and 0.25. High zeta potentials (>29.0 in modulus) indicated stable formulations. The NLCs effectively encapsulated the EOs, achieving encapsulation efficiencies between 84.6 to 100% w/w of marker compound. The EOs-loaded NLCs reduced the SARS-CoV-2 virion count, exceeding 2 logs over the control. NLCs loaded with Lippia sidoides and Syzygium aromaticum EOs represent an innovative strategy for combating SARS-CoV-2.

Development of a fluorescence-based excipient screening for improved stability and shelf-life of recombinant chitin deacetylase

Chitin deacetylase (CDA) modifies chitin into chitosan by removing acetyl groups, but its inherent instability poses a challenge for successful crystallisation. Despite limited successes in crystallizing CDAs, prior attempts with recombinant chitin deacetylase (BaCDA) failed due to poor stability. To address this, we propose an enzyme buffer formulation as a cost-effective strategy to enhance stability, prolong shelf life, and increase the likelihood of crystallisation. Utilizing the high-throughput screening technique FTSA, we developed a screening method correlating BaCDA stability with its activity. The optimised formulation comprises 50 mM Tris-HCl buffer pH 7, 1 M NaCl, 20 % glycerol, and 1 mM Mg2+ as excipients. This formulation significantly improves BaCDA's thermostability (140.47 % increase) and enzyme activity (2.9-fold enhancement). BaCDA remains stable in the formulated buffer at −20 °C and −80 °C for 30 days and at 4 °C for 15 days. The current study has designed a high-throughput screening method approach to assess the stability of CDA enzyme formulations. The results of this study could contribute to the exploration of formulation elements that enhance the structural stability of CDA, thereby facilitating investigations into the enzyme's structure-function relationships.

Stability and Retention of Nanoemulsion Formulations Incorporating Lavender Essential Oil

Lavender essential oil (LEO) is applied topically for its soothing properties, serving not only as an antiseptic in wound care but also as an insect repellent. This study investigates the impact of carrier systems on LEO encapsulation, stability, and release kinetics for potential skincare applications. The LEO carrier impact on skin hydration and barrier function was also evaluated. Conventional emulsions (CEs) and nanoemulsions (NEs) with (CELs and NELs, respectively) and without LEO incorporation were analyzed for physicochemical properties, stability, and release mechanisms. The droplet size distribution and ζ-potential remained consistent in both CE and CEL, showing the minimal influence of LEO on those parameters. NE and NEL exhibited enhanced stability and higher LEO retention compared to CE and CEL (37.38 mg/mL ± 0.48 mg/mL and 50.96 mg/mL ± 2.00 mg/mL, respectively, p < 0.05), suggesting NE as a superior carrier system for LEO delivery. NEL retained LEO over 60 days at 4 °C without a significant reduction while CEL showed a notable reduction of 94.93% ± 0.08%. Release kinetics analysis showed zero-order release kinetics of LEO from both CEL and NEL (R2: 0.973 and 0.952, respectively), revealing a diffusion-based mechanism, particularly evident in NE formulations, supporting the controlled and sustained release of LEO constituents. NEL also promoted quicker skin barrier repair and enhanced skin hydration, sustaining effects for up to 120 min post application, surpassing CEL’s performance. These findings contribute to understanding the carrier system effects on LEO delivery and underscore NE as a promising vehicle for skincare applications. Further research should explore underlying mechanisms and conduct long-term safety and efficacy studies to fully exploit the therapeutic potential of NE in dermatological applications.

Environmentally responsive systems for topical administration of copaiba oil-resin: The effect of carbomer 974P on the mechanical, rheological, drug release and skin permeation

Topical wound therapy using copaiba oil-resin (CO) can be improved by combining it with a thermoresponsive bioadhesive release system. Emulgel systems composed of the bioadhesive carbomer 974P (C974P) and the thermoresponsive poloxamer 407 (P407) can prolong the CO contact time with the skin and facilitate the drug permeation through the skin layers. The aim of this work was to develop and investigate the C974P's effect on rheological, mechanical, bioadhesive, in vitro drug release and ex vivo skin permeation properties of this system. The system development was based on a 23 (plus two central points) factorial design and the influence of different amounts of C974P on formulations was investigated. C974P enabled the formation of viscous and stable emulgels, and could structure with P407 and CO, resulting on physicochemical stable formulations. Formulation composed of 0.5 % (w/w) C974P, 20 % (w/w) P407 and 8 % (w/w) CO (F8) displayed improved properties. F8 exhibited extended release, enhanced bioadhesive strength, improved hardness, compressibility, elasticity, adhesiveness, cohesiveness, pseudoplasticity with yield value, thixotropy, and high viscoelasticity. It also displayed skin permeation and retention. The P407's high capacity to form micelles with CO enabled their integration into the polymeric matrix formed by C974P, resulting in viscous and stable gel.

Enhancement in Dissolution Profile of Cilnidipine by Nanonization Technique: Optimization by Box-Behnken design

Objectives: Cilnidipine has limited 25-30% of bioavailability due to BCS class II category drug. The aim of present work was to improve the solubility followed by dissolution rate of cilnidipine by formulation of nanosuspension. Materials and Methods: The nanosuspensionwas developed usingnanoprecipitation techniqueaidingultra-sonication with solvent (Dimethyl sulfoxide), antisolvent (water) and stabilizer (polyvinyl alcohol). The nano formulation was statistically optimized using Design Expert software by theBox-Behnken design. The concentration of Poly Vinyl Alcohol, Volume of Antisolvent and Stirring Time were considered as independent factors whereas Particle size and polydispersity index were considered as dependent factors. Results: The particle size of nanosuspension was found 178.57nm with narrow polydispersity index of 0.130. The microscopy study confirmed amorphous nature particles with rough surface. The zeta potential of 4.55 ±2.78 for optimized formulation finds stability of formulation during storage. The differential scanning calorimetry study and X-ray diffraction pattern showed the crystalline cilnidipine drug was converted to amorphous form upon precipitation into nanoparticles. Due to the nanonization of cilnidipine, the dissolution profile was noted as 92.41±3.56% which was significantly improved as compared with plain drug release data. The stability data showed satisfactory result for 2 months. Conclusion: It is summarized that the nanoprecipitation technique with ultra-sonication is approaching method for the formulation of homogenous nanosuspension with uniform sized dispersion of cilnidipine. Therefore, it can be assumed that the upon the enhancement in dissolution rate, the cilnidipine loaded nanosuspension may lead to improved absorption of drug from intestine followed by significant improvement in bioavailability.

Investigation on the Combined Effect of Hydroxypropyl Beta-Cyclodextrin (HPβCD) and Polysorbate in Monoclonal Antibody Formulation.

Monoclonal antibodies require careful formulation due to their inherent stability limitations. Polysorbates are commonly used to stabilize mAbs, but they are prone to degradation, which results in unwanted impurities. KLEPTOSE® HPβCD (hydroxypropyl beta-cyclodextrin) has functioned as a stable stabilizer for protein formulations in our previous research. The current study investigates the collaborative impact of combining polysorbates and HPβCD as excipients in protein formulations. The introduction of HPβCD in formulations showed it considerably reduced aggregation in two model proteins, bevacizumab and ipilimumab, following exposure to various stress conditions. The diffusion interaction parameter revealed a reduction in protein-protein interactions by HPβCD. In bevacizumab formulations, the subvisible particle counts per 0.4 mL of samples in commercial formulations vs. formulations containing both HPβCD and polysorbates subjected to distinct stressors were as follows: agitation, 87,308 particles vs. 15,350 particles; light, 25,492 particles vs. 6765 particles; and heat, 1775 particles vs. 460 particles. Isothermal titration calorimetry (ITC) measurement indicated a weak interaction between PS 80 and HPβCD, with a KD value of 74.7 ± 7.5 µM and binding sites of 5 × 10-3. Surface tension measurements illustrated that HPβCD enhanced the surface activity of polysorbates. The study suggests that combining these excipients can improve mAb stability in formulations, offering an alternative for the biopharmaceutical industry.

Preparation and Evaluation of Niosomal Gel Loaded With Combination of Isotretinion and Clindamycin

The objective of the present study was to formulate topical niosomal gel loaded with combination of Isotretinion and Clindamycin for the beneficial of acne patients, to provide sustained release effects, to prevent their side effects. First generation topicals retinoids (Isotretinion) and antibacterials (Clindamycin) target comedones, Propionibacterium acnes or inflammation. The combination of Isotretinion and Clindamycin is reported to treat almost all type of acne and have potential to increase both efficacies, patient adherence as compared to single agent treatment. Purpose of this study was to develop a stable formulation that allows progressive follicle penetration and increased efficacy. Preformulation studies such as melting point, FTIR spectroscopy, UV spectroscopy, solubility, partition coefficient (log P) were performed for both drugs. The niosomal combination of both drugs was incorporated into the carbopol gel. The pH and viscosity of gel was performed.

Encapsulated allyl isothiocyanate improves soil distribution, efficacy against soil-borne pathogens and tomato yield.

Crop quality, yield and farmer income are reduced by soil-borne diseases, nematodes and weeds, although these can be controlled by allyl isothiocyanate (AITC), a plant-derived soil fumigant. However, its efficacy against soil-borne pathogens varies, mainly because of its chemical instability and uneven distribution in the soil. Formulation modification is an effective way to optimize pesticide application. We encapsulated AITC in modified diatomite granules (GR) and measured the formulation's loading content and stability, environmental fate and efficacy against soil-borne pathogens, and its impact on the growth and yield of tomatoes. We observed that an AITC loading content in the granules of 27.6% resulted in a degradation half-life of GR that was 1.94 times longer than 20% AITC emulsifiable concentrate in water (EW) and shorter than AITC technical (TC) grade. The stable and more even distribution of GR in soil resulted in relatively consistent and acceptable control of soil-borne pathogens. Soil containing AITC residues that remained 10-24 days after GR fumigation were not phytotoxic to cucumber seeds. GR significantly reduced soil-borne pest populations, and tomato growth and yield increased as AITC dosage increased. GR containing an AITC dose of 20 g m-2 effectively controlled pathogens in soil for about 7 months and improved tomato yield by 108%. Our research demonstrates the benefits of soil fumigation with loaded AITC over other formulations for effective pest control, and improved tomato plant growth and fruit yield. Fumigant encapsulation appears to be a useful method to improve pest and disease control, environmental performance and fumigant commercial sustainability. © 2024 Society of Chemical Industry.

Advances in Nanocarrier Systems for Overcoming Formulation Challenges of Curcumin: Current Insights.

Curcumin, an organic phenolic molecule that is extracted from the rhizomes of Curcuma longa Linn, has undergone extensive evaluation for its diverse biological activities in both animals and humans. Despite its favorable characteristics, curcumin encounters various formulation challenges and stability issues that can be effectively addressed through the application of nanotechnology. Nano-based techniques specifically focused on enhancing solubility, bioavailability, and therapeutic efficacy while mitigating toxicity, have been explored for curcumin. This review systematically presents information on the improvement of curcumin's beneficial properties when incorporated, either individually or in conjunction with other drugs, into diverse nanosystems such as liposomes, nanoemulsions, polymeric micelles, dendrimers, polymeric nanoparticles, solid-lipid nanoparticles, and nanostructured lipid carriers. Additionally, the review examines ongoing clinical trials and recently granted patents, offering a thorough overview of the dynamic landscape in curcumin delivery. Researchers are currently exploring nanocarriers with crucial features such as surface modification, substantial loading capacity, biodegradability, compatibility, and autonomous targeting specificity and selectivity. Nevertheless, the utilization of nanocarriers for curcumin delivery is still in its initial phases, with regulatory approval pending and persistent safety concerns surrounding their use.

A Retrospective Analysis of Polymer Selection Using Solvent Casting: Formulation and DoE Optimization of the Amorphous Solid Dispersion of Amoxicillin Trihydrate by a Spray Drying Method

Background. Amoxicillin trihydrate possesses poor solubility, compressibility, and flow behavior. Amorphous solid dispersion prepared by spray drying could solve all three problems at the same time. Objective. To prepare amorphous solid dispersion after screening of polymers by solvent casting method using a spray drying method. Methods. The solvent casting method was used to screen polymers, PVP/VA S-630, PVP K30, Soluplus, PEG 4000, HPMC AS, and HPMC HP55, in 1 : 1 and 2 : 3 ratios and followed by spray drying after polymer selection. Results. The dissolution performance of the formulation improved with time. The optimum feed rate and feed concentration were found to have an impact on the flow properties and particle size of spray-dried formulations, and they were selected as independent variables in a 32 full factorial statistical design. The ANOVA and regression analysis suggest that the developed regression model has a significant overall fit to the data and can explain a substantial proportion of the variability in the dissolution at 10 minutes. The optimized batch was selected based on the decisive factors of minimum and maximum values of response variables. Overall, the optimized batch demonstrated improved characteristics in terms of percentage yield (32.81%), dissolution at 10 min (49.70%), and angle of repose at 31.42°. Conclusion. This study provides valuable insights into optimizing formulation strategies for preserving the amorphous state of drugs and contributes to the development of stable pharmaceutical formulations.

Antioxidant Activity Of Nanoemulsion Of Beet Fruit Extract Using The Dpph Method

Free radicals are one of many forms of reactive oxygen sorts known for having unpaired electrons. The presence of free radicals in the body can cause damage such as premature aging, characterized by the appearance of wrinkles. This damage can be countered with antioxidant compounds. Beetroot is one of the fruits with antioxidant properties due to the presence of betacyanin compounds from the flavonoid group. This research aims to identify the antioxidant activity and IC50 value of beetroot (Beta vulgaris L.) extract nanoemulsion formulations using the DPPH method. Nanoemulsion formulations were prepared with varying concentrations of beetroot extract at 1% (X1), 3% (X2), and 5% (X3) to determine which concentration has the best antioxidant activity. Quality evaluation of the nanoemulsion formulations was also conducted, including organoleptic tests, pH tests, and homogeneity tests. The results showed that the beetroot extract nanoemulsion formulations have antioxidant activity and meet the requirements for physical properties and formulation stability. Nanoemulsion formulations with 5% (X3) beetroot extract content exhibited the best antioxidant activity with an IC50 value of 136.475 ppm.

Development of Nanostructured Lipid Carrier-Loaded Flavonoid-Enriched Zingiber officinale.

Flavonoids, which are bioactive molecules found in Zingiber officinale, have been widely used as antioxidant and anti-inflammatory drugs. The presence of nanostructured lipid carriers (NLCs) as sophisticated delivery systems for bioactive compounds, such as flavonoids, can increase their bioavailability and stability, thus potentially producing better therapeutic effects. This study aimed to develop an anti-inflammatory topical gel using NLC-containing flavonoids derived from Zingiber officinale. The NLC formulation was prepared using stearic acid, a mixture of medium-chain triglycerides and isopropyl myristate, Tween 20, and Span 20 by using a hot homogenization method. The total flavonoid content obtained through sequential maceration stages was 4.04 mg of QUE/g of dry extract. The highest encapsulation efficiency of flavonoid-loaded NLC was observed at a flavonoid, Zingiber officinale extract (ZOE) concentration of 2%. It was found that a ZOE concentration of 0.4% provided excellent stability with a particle size of 302-344 nm and a polydispersity index of 0.14-0.23 after 28 days of observation. Morphological analysis of the ZOE-loaded NLC revealed a stable and well-developed formulation with a fairly uniform distribution. The presence of distinctive and uniformly distributed single particles suggests a promising alternative drug delivery system for conventional topical preparations. ZOE-loaded NLC gel showed solid-like properties and higher quality stability than the gel.

Rosemary and neem: an insight into their combined anti-dandruff and anti-hair loss efficacy

Dandruff, a common scalp disorder characterized by flaking dead skin, is often treated with conventional topical products. However, limitations exist due to potential side effects and high costs. Therefore, searching for natural, cost-effective solutions for dandruff and hair loss is crucial. Rosemary herb and neem tree, both cultivated in Egypt, possess well-documented anti-inflammatory properties derived from their rich phenolic phytoconstituents. This study formulated a standardized combined extract of rosemary and neem (RN-E 2:1) into hair gel and leave-in tonic formats. This extract demonstrated superior efficacy against Malassezia furfur (a causative agent of dandruff) and Trichophyton rubrum (associated with scalp disorders) compared to the conventional antifungal agent, ketoconazole. The combined extract (RN-E 2:1) also exhibited potent anti-inflammatory activity. Additionally, the suppression of iNOS expression is considered concentration-dependent. Quality control verified formulation stability, and ex-vivo studies confirmed effective ingredient penetration into the epidermis, the primary site of fungal presence. Remarkably, both formulations outperformed the standard treatment, minoxidil in hair growth trials. These findings highlight the potential of natural extracts for scalp and hair health.

Structural elucidation and development of azelaic acid loaded mesoporous silica nanoparticles infused gel: Revolutionizing nanodrug delivery for cosmetics and pharmaceuticals

This research aimed to enhance dermal delivery and optimize depigmentation therapy by designing mesoporous silica nanoparticles (MSNs) encapsulating azelaic acid (AZA) within a gel matrix. The MSNs were prepared using the sol-gel method. After subsequent processes, including acid extraction and drug loading, were then elucidated through PDI, size, zeta-potential, entrapment efficiency, nitrogen adsorption assay, FE-SEM, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and tyrosinase inhibition assay, were employed to assess the formulation. In-vitro stability tests for both AZA-MSN gel (AZCG) and AZA-loaded mesoporous silica gel (AZMG) were conducted at 8 °C, 25 °C, 40 °C, and 40 °C + 75 % RH, encompassing assessments of color, liquefaction, pH, and conductivity. Our findings showed a notable entrapment efficiency of 93.46 % for AZA-MSNs, with FE-SEM illustrating porous spherical MSNs. The particle size of AZA-MSNs was determined to be 211.9 nm, with a pore size of 2.47 nm and XRD analysis confirmed the amorphous state of AZA within the MSN carriers. Rheology examination indicated a non-Newtonian flow, while ex-vivo rat skin permeation studies conducted in a phosphate buffer (pH = 5.5) demonstrated a biphasic release pattern with 85.53 % cumulative drug permeation for AZA-MSNs. Overall, the study endorse the potential of AZA-MSNs as an efficacious and stable formulation for AZA delivery, highlighting their promise in addressing pigmentation concerns compared to conventional approaches.

Calcium Chloride as a Novel Stabilizer for Foot-and-Mouth Disease Virus and Its Application in the Vaccine Formulation.

The thermal stability of the in-house-developed foot-and-mouth disease (FMD) type O and A viruses was evaluated, and the O Jincheon virus was found to exhibit the lowest thermal stability. To overcome this instability, we proposed a novel stabilizer, calcium chloride. The thermal stability of FMDVs increased up to a CaCl2 concentration of 10 mM, and it had a decreasing trend at >30 mM. The O Jincheon virus showed a significant decrease in the amount of antigen over time at 4 °C. In contrast, the samples treated with CaCl2 showed stable preservation of the virus without significant antigen loss. After the CaCl2-formulated vaccine was administered twice to pigs, the virus neutralization titer reached approximately 1:1000, suggesting that the vaccine could protect pigs against the FMDV challenge. In summary, the O Jincheon virus is difficult to utilize as a vaccine given its low stability during storage after antigen production. However, following its treatment with CaCl2, it can be easily utilized as a vaccine. This study evaluated CaCl2 as a novel stabilizer in FMD vaccines and may contribute to the development of stable vaccine formulations, especially for inherently unstable FMDV strains.

Formulation and Evaluation of Liposomes containing Metformin Hydrochloride

The characterization and evaluation of metformin hydrochloride-loaded liposomal formulations are critical processes aimed at assessing their effectiveness and suitability for medical use. These formulations, composed of small synthetic vesicles called liposomes, are designed to enhance the delivery and efficacy of metformin, a widely used medication for managing type 2diabetes. Liposomes, with their unique blend of hydrophobic and hydrophilic properties, offer promising advantages in drug delivery. One key aspect of this process involves characterizing the liposomal formulations. This characterization entails examining various parameters such as size, surface charge, morphology, and encapsulation efficiency. Techniques like dynamic light scattering, zeta potential analysis, and microscopy are employed for this purpose, providing valuable insights into the physical properties of the liposomes. Additionally, the stability of the liposomal formulations is thoroughly assessed. This involves evaluating their physical and chemical stability under various storage conditions, including temperature and humidity variations, over a defined period. Ensuring the stability of the formulations is essential for maintaining their efficacy during storage and transportation. Finally, if feasible, preclinical pharmacokinetic studies are conducted in appropriate animal models to evaluate the bio distribution, systemic exposure, and pharmacokinetic parameters of metformin hydrochloride following administration of the liposomal formulations. These studies help determine the drug's behavior in living organisms and its potential therapeutic benefits

Extension of ultrafiltered cheese shelf life using edible coatings containing supercritical rosemary, thyme and coriander extracts as antimicrobial agents

Currently, supercritical extraction allows for the “green” isolation of plant antimicrobial components and their subsequent use in the food industry. The study aims to extend the shelf life of ultrafiltered cheese by using edible coatings containing supercritical fluid extracts (SFEs) of Rosmarinus officinalis L., Thymus vulgaris and Coriandrum sativum L. The SFEs chemical profiling was studied using GC-MS. Ten emulsion coating formulations were prepared using whey protein concentrate and the SFEs. The antimicrobial activity of coatings was assessed using well diffusion assay. Their effect on shelf life, physicochemical and sensory characteristics of the ultrafiltered cheese samples was investigated. GC/MS analysis of Rosmarinus officinalis L., Thymus vulgaris and Coriandrum sativum L. showed that 1,8-Cineol, m-Cymene, and Linalool are the major compounds with 35.4, 41.6, and 61.3 % respectively. The particle size of all formulations ranged from 157.3 to 453.7 nm and had a broad size distribution with a low Polydispersity Index values ranging from 0.35 to 0.49. The obtained Zeta potential values from −27.8 to −36.0 mV indicate the stability of the SFE-emulsion formulations. The antimicrobial trials showed that formulations, that mainly contained Thymus vulgaris, demonstrated more inhibition effect against all tested strains than other formulas with inhibition zone diameter ranged between 10.7 and 16.3 mm and followed by formulations, that mainly contained Rosmarinus officinalis L., with inhibition zones diameter between 6.7 and 11.7 mm depending on microbial type. Combining rosemary and coriander extracts synergistically enhanced their antimicrobial effect and extended the shelf life of cheese beyond 40 days.

Effects of Clay Contamination on the Stability of Aqueous Foams at High Pressure

Summary Because of its low density, high viscosity, and good hole-cleaning performance, foam is used in the industry as a drilling and completion fluid. Due to these unique properties, foam can be applied in underbalanced drilling. After an extended period, however, the degradation of its thermodynamically unstable structure leads to the gradual loss of these valuable properties. While a number of research studies have been performed to investigate foam flow behavior, more is needed to know about their drainage characteristics and stability at high pressure. The primary goal of this investigation is to examine the effects of clay contaminants on the drainage of foam at high pressure. Moreover, the results and findings of this study not only show the effect of clay contaminants on foam stability but also help develop clay-based stable foam formulations without using chemicals that have the potential to contaminate groundwater or seawater. This paper shows the findings of an investigation on the aqueous foam stability in the presence of clay (bentonite and kaolinite) contaminants. Experiments were conducted at ambient temperature while varying foam quality and clay concentration at a constant pressure of 6.8 MPa. During the study, the foam was created in a flow loop. After generation, its rheology and stability were measured using a pipe viscometer and a vertical test tube (column). The hydrostatic pressure profile in the column was measured with time to assess foam drainage. The results show that clay type and concentration affect aqueous foam drainage and flow behavior. The impact of clay on these foam properties is controlled by foam quality. Adding more than 2.5% bentonite considerably enhanced foam stability and viscosity. In contrast, the impacts of kaolinite on these foam properties were minimal at the same concentration. The drainage became negligible when 5% bentonite was added to the foam. However, at a reduced concentration (2.5%), bentonite addition was only an effective stabilizer for low-quality foam (40%). Microscopic examination of the foams prepared under ambient conditions demonstrated the accumulation of colloidal particles at the plateau borders and nodes that block the drained liquid flow and reduce drainage.

Optimizing Verapamil Hydrochloride In-situ Delivery: A Strategic Formulation Approach using Box-Behnken Design for Enhanced Performance and Comprehensive Evaluation of Formulation Parameters

This study focuses on formulating and assessing an in-situ gastro-retentive gel for precise delivery of verapamil hydrochloride to the stomach, aiming to extend its residence time and improve targeted delivery. Gels were synthesized in-situ using a cation-controlled gelation method, incorporating varied blends of pectin and HPMCK4M. Design Expert’s box behnken design was employed to assess responses such as buoyancy lag time, water uptake, and cumulative drug discharge. Results revealed that the developed gels exhibited a total float time exceeding 10 hours, with formulation T-2 showing the least floating lag time and a cumulative drug release of 99.40 ± 3.24% over 10 hours. This suggests effective prolongation of the gastric residence time, enabling controlled verapamil hydrochloride release. Additional evaluations, including appearance, pH, viscosity, in-vitro gel formation, drug content, density, and gel force, supported the robustness of the developed gels. Subsequent in-vitro dissolution and stability studies affirmed consistent active ingredient content, highlighting formulation stability over time. In conclusion, this study demonstrates that the in-situ gels effectively extend gastric residence time, facilitating controlled verapamil hydrochloride release, marking significant advancements in drug delivery systems and targeted drug delivery within the gastrointestinal tract.