Accelerated Stability Studies Research Articles

IN SILICO DOCKING STUDY OF HERBAL COMPOSITION AND DEVELOPMENT OF MOUTH DISSOLVING TABLETS FOR COMMON RESPIRATORY DISEASES THEREOF

Objective: The present study aims to develop a novel mouth dissolving tablets containing a combination of herbal extracts and a bioactive constituent and evaluating it for activity against common respiratory diseases (in silico studies). Methods: Docking study was done to provide a scientific foundation, keeping the traditional knowledge as a base. Four trial batches were developed. The final batch was then formulated and various pre and post-compression and assays were performed to evaluate the formation of good quality of product. The final batch was prepared by the method of direct compression and taken for accelerated stability studies. Results: The final batch containing 10 % active ingredients, 7.5 % super-disintegrant and 47 % diluent was found to be stable, easily producible and economic. Conclusion: This research work grasps possibilities for researchers in the development and evaluation of mouth-dissolving tablets with significant bioactive potential against common respiratory diseases.

Temperature and pH-dependent stability of fentanyl analogs: Degradation pathways and potential biomarkers.

The collection, storage, and transport of samples prior to and during analysis is of utmost importance, especially for highly potent analogs that may not be present in high concentrations and are susceptible to pH or thermally mediated degradation. An accelerated stability study was performed on 17 fentanyl analogs (fentalogs) over a wide range of pH (2-10) and temperature (20-60°C) conditions over 24 h. Dilute aqueous systems were used to investigate temperature and pH-dependent kinetics using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Liquid chromatography-quadrupole/time-of-flight-mass spectrometry (LC-Q/TOF-MS) was used for structural elucidation of degradants. With the exception of remifentanil, all fentalogs evaluated were stable at pH 6 or lower. Fentalogs were generally unstable in strongly alkaline environments and at elevated temperatures. Remifentanil was the least stable drug and N-dealkylated fentalogs were the most stable. Fentanyl degraded to acetylfentanyl, norfentanyl, fentanyl N-oxide, and 1-phenethylpyridinium salt (1-PEP). A total of 26 unique breakdown products were observed for 15 of the fentanyl derivatives studied. Common degradation pathways involved N-dealkylation, oxidation of the piperidine nitrogen, and β-elimination of N-phenylpropanamide followed by oxidation/dehydration of the piperidine ring. Ester and amide hydrolysis, demethylation at the propanamide, and O-demethylation were observed for selected fentalogs only. The potential for analyte loss should be considered during the pre-analytical phase (i.e., shipping and transport) where environmental conditions may not be controlled, as well as during the analysis itself.

Hemocompatible and biocompatible hybrid nanocarriers for enhanced oral bioavailability of paclitaxel: in vivo evaluation

Oral administration of BCS class IV anticancer agents has always remained challenging and frequently results in poor oral bioavailability. The goal of the current study was to develop hybrid nanoparticles (HNPs) employing cholesterol and poloxamer-407 to boost paclitaxel's (PTX) oral bioavailability. A series of HNPs with different cholesterol and poloxamer-407 ratios were developed utilizing a single-step nanoprecipitation technique. The PTX loaded HNPs were characterized systematically via particle size, zeta potential, polydispersity index, surface morphology, in vitro drug release, FTIR, DSC, XRD, acute oral toxicity analysis, hemolysis evaluation, accelerated stability studies, and in vivo pharmacokinetic analysis. The HNPs were found within the range of 106.6±55.60 – 244.5±88.24 nm diameter with the polydispersity index ranging from 0.20±0.03 – 0.51±0.11. SEM confirmed circular, nonporous, and smooth surfaces of HNPs. PTX loaded HNPs exhibited controlled release profile. The compatibility between the components of formulation, thermal stability, and amorphous nature of HNPs were confirmed by FTIR, DSC, and XRD, respectively. Acute oral toxicity analysis revealed that developed system have no deleterious effects on the animals' cellular structures. HNPs demonstrated notable cytotoxic effects and were hemocompatible at relatively higher concentrations. In vivo pharmacokinetic profile (AUC0-∞, AUMC0-∞, t1/2, and MRT0-∞) of the PTX loaded HNPs was improved as compared to pure PTX. It is concluded from our findings that the developed HNPs are hemocompatible, biocompatible and have significantly enhanced the oral bioavailability of PTX.

Development, optimization, and in-vivo bioavailability study of erlotinib hydrochloride loaded microsponge for colon targeting

The present investigation aimed to develop as well as optimize microsponge containing erlotinib hydrochloride (ETB) that was composed of ethyl cellulose (EC) and pectin. The water solubility and enzymatic susceptibility make it easier to fabricate the microsponge formulation. The ETB loaded microsponge was manufactured using quasi-emulsion solvent diffusion process. By this technique, organic solution of the primary component is emulsified with stabilizing agents that are soluble in water. To design the formation of the microsponge, 32 factorial design was implemented. It was investigated how the response variables like particle dimension, entrapment efficiency, ETB diffusion at 12 ​h were influenced by independent variables such as rotation speed and the pectin to ethyl cellulose ratio. The optimal microsponge formulation loaded with ETB (F0) composed of 1:2.8 ratio of pectin to ethyl cellulose (EC) with stirring rate at 478 ​rpm. Particle dimension, entrapment efficiency, and ETB release at 12 ​h from optimized formulation were shown 104.89 ​± ​0.62 ​nm, 82.36 ​± ​2.85 ​%, and 85.49 ​± ​1.84 ​% respectively. The In-vivo pharmacokinetic study conducted on rabbit model shows a significant improvement in bioavailability. The optimized microsponge formulation has been found to have a higher Cmax than the ETB aqueous suspension. The stability of the formulation has been determined by the accelerated stability study of optimized microsponge formulation. This study indicated that the optimized formulation retained its stability even after 90days. In general, the present investigation demonstrated that drug loaded microsponge based formulation is a suitable method to improve the therapeutic efficacy and bioavailability of ETB.

Exploring the potential of carbocisteine loaded microparticulate system by using ccd model for the treatment of respiratory infections

Background: Multi-particulate drug delivery systems (microbeads) deliver drugs over an extended period, distributing them evenly throughout the gastrointestinal tract and minimizing local irritation. Microbeads are small, solid, free-flowing particulate carriers that contain drug particles that have been dispersed and are either crystalline in solution. Aim: The present work explores the potential of the carbocisteine-loaded floating microparticulate drug delivery system. Methodology: Floating microbeads were prepared using the ionotropic gelation method and optimized using Central Composite Design. Result and discussion: Floating microbeads of prepared carbocisteine were evaluated for the FTIR study, which reveals no interaction between the drug and other excipients. Buoyancy time, drug content, particle size, and % drug release were also characterized; it found that drug release was 90.24 %, up to 17 hours, 250 to 220 µm, and drug content 96.67%, respectively, for the optimized batch. An accelerated stability study was performed, showing that the formulation was stable. Floating microparticulate drugs were prepared, and batch B-3 was optimized based on in-vitro buoyancy and release patterns. The floating ability of the beads was observed visually for 10 to 17 hr, and an increase in polymer concentration decreased the swelling of the beads. Conclusion: The results obtained from the formulation batch B-3 show good results for all the parameters tested. Floating microbeads could be the best possible approach to deliver drugs with the benefit of reduced dosing frequency

Design of Optimized Solid Lipid Nanoparticles of Montelukast Sodium and Assessment of Oral Bioavailability in Experimental Model.

The objective of the reported work was to develop Montelukast sodium (MS) solid lipid nanoparticles (MS-SLNs) to ameliorate its oral bio-absorption. Herein, the highpressure homogenization (HPH) principle was utilized for the fabrication of MS-SLNs. The study encompasses a 23 full factorial statistical design approach where mean particle size (Y1) and percent entrapment efficiency (Y2) were screened as dependent variables while, the concentration of lipid (X1), surfactant (X2), and co-surfactant (X3) were screened as independent variables. The investigation of MS-SLNs by DSC and XRD studies unveiled the molecular dispersion of MS into the SLNs while TEM study showed the smooth surface of developed MSSLNs. The optimized MS-SLNs exhibited mean particle size (MPS) = 115.5 ± 1.27 nm, polydispersity index (PDI) = 0.256 ± 0.04, zeta potential (ζ) = -21.9 ± 0.32 mV and entrapment efficiency (EE) = 90.97 ± 1.12 %. The In vivo pharmacokinetic study performed in Albino Wistar rats revealed 2.87-fold increments in oral bioavailability. The accelerated stability studies of optimized formulation showed good physical and chemical stability. The shelf life estimated for the developed MS-SLN was found to be 22.38 months. At the outset, the developed MS-SLNs formulation showed a significant increment in oral bioavailability and also exhibited excellent stability in exaggerated storage conditions.

Solidification of deep eutectic solvent containing fimasartan through wet impregnation and exploration of flow attributes by modified SeDeM-SLA expert system

The solidification of deep eutectic solvent (DES) through wet impregnation techniques on inert solid carriers is an interesting approach that offers better processing attributes and excellent stability. Herein, DES of Fimasartan (FS) was developed to improve its solubility and bioavailability. The selected DES-FS was solidified by wet impregnation method employing Nesulin US2 and Aerosil 200. The SeDeM-SLA (solid–liquid adsorption) system was employed to investigate flow attributes of solidified DES-FS. Further, the selected solidified DES-FS (A) was characterized by Fourier transforms infrared spectroscopy (FTIR), Powder X-ray diffraction (PXRD), Differential scanning calorimetry (DSC), Scanning electron microscopy (SEM). The DES comprising Choline Chloride (ChCl): Glycerol (Gly) (1:3) revealed maximum drug solubility (35.6 ± 2.2 mg/mL) and thus opted for solidification. Solidification through wet impregnation was employed using 1:0.5 ratios (DES-FS to carriers). The Index of Good Flow (IGF) value was calculated from the SeDeM-SLA expert system, which indicates the better flow characteristics of solidified DES-FS, particularly with Neusilin US2 [SDES-FS (A)]. The solid-state evaluation data of SDS-FS (A) suggested a transition of FS to an amorphous form, resulting in an increment in solubility and dissolution. A similar trend was reported in the in vivo pharmacokinetic study, which indicated a 2.9 folds increment in the oral bioavailability of FS. Furthermore, excellent stability, i.e., a shelf life of 28.44 months, reported by SDES-FS (A) in accelerated stability studies, suggests better formulation perspectives. In a nutshell, the present study evokes the potentiality of performing solidification through wet impregnation and successful implementation of the SeDeM-SLA expert model, which could find wide applications in pharmaceutical science.

Diltiazem Hydrochloride Floating Matrix Tablet: Formulation and in vitro-in vivo Evaluation.

Diltiazem hydrochloride is a calcium channel-blocker with a plasma elimination half-life of 4.4 ± 1.3 h and has a narrow absorption window. So, this work aimed to prepare a gastro-retentive floating matrix tablet. The direct compression method was used to manufacture tablets. 32 factorial design was applied for optimization, taking Hydroxypropyl Methylcellulose K100M (HPMC K 100M) and the amount of sodium bicarbonate as independent factors and cumulative percentage release at 1 h, at 6 h, and at 12 h and floating lag time as dependent variables. The high amount of HPMC K100M and sodium bicarbonate shows good results. The optimized preparation was evaluated for differential scanning calorimetry, in-vivo gastric retention in male albino rabbits, kinetic modeling, and stability study. An in vivo study revealed gastric retention of tablets up to 6 h in healthy male Albino rabbits. The stability study indicated no significant change in the buoyancy and release profiles of the drug. From this study, it can be concluded that the gastro-retentive diltiazem hydrochloride floating matrix tablet was successfully prepared and retained inside the rabbit stomach for up to 6 h and was stable under accelerated stability study.

A novel compounded cyproheptadine hydrochloride oral solution: Accelerated stability study and effects on glucose and lipid metabolism in Wistar rats

The present study developed a compounded oral solution (COS) containing an active component cyproheptadine hydrochloride (CY) in association with pharmaceutical adjuvants. The main objective is to demonstrate the stability of this solution and the in vivo effects on serum and liver parameters of glucose and lipid metabolism. After 180 days of analysis the COS showed physicochemical stability (pH and specific gravity) when submitted to different temperatures (24 °C and 40 °C), but the chemical stability, presented by the content of CY (%) in the formulation, showed that the degradation rate of CY increased 20x when submitted to a stress condition (40 °C). Male Wistar rats were treated with IOS 1.5 (industrial oral solution 1.5 mg.kg-1) or saline for 21 days and IOS 5.0 or COS (5 mg.kg-1) or placebo by gavage for 23 days. Treatment with IOS 1.5 increased liver cholesterol by 30 % without changing liver and body weight in this group. In contrast, treatment with IOS and COS (5 mg.kg-1) increased final body weight by 8 % compared to placebo. Interestingly, the COS group had increased liver glycogen accompanied by reduced food intake compared to IOS. However, COS and IOS 5.0 did not induce changes in adipose tissue weight, liver weight, as well as serum glucose, triacylglycerol and cholesterol levels. This work provides us with data that prove the stability of the compound solution at room temperature, as well as inducing an increase in the final body weight of rats with no alteration in glucose and lipid metabolism.

Besifloxacin HCl Ophthalmic In situ Gel: Design, Optimization, In vitro and Ex vivo Investigation

The present work aimed to formulate and evaluate Besifloxacin Hydrochloride (HCl) ophthalmic in situ gel for conjunctivitis, based on temperature triggered gelation system to increase ocular residence time, bioavailability and patient compliance. Different formulations were prepared by using Poloxamer 407 and Poloxamer 188 as temperature sensitive as well as mucoadhesive polymers. Design expert software version 11 was used to optimized the formula. Optimized batch having Poloxamer 407 (24.80% w/v) and Poloxamer 188 (14.53% w/v) was evaluated for visual appearance, clarity, gelation temperature, gelling capacity, rheological property, ex vivo, in vitro release and accelerated stability studies. Histopathological study was carried out using Goat cornea and revealed no change in histopathology of the tissues. Formulation was found to be effective against the Escherichia coli and Staphylococcus aureus. Cumulative % drug release of Besifloxacin HCl ophthalmic in situ gel after 8 hours was found to be 96.47 %.

FORMULATION AND STABILITY EVALUATION OF ANTI-OBESITY NUTRACEUITCAL BLEND OF WHITE KIDNEY BEAN EXTRACT (PHASEOLUS VULGARIS L.), PROPOLIS ETHANOLIC EXTRACT AND CRPIC3

Objective: This study aimed to formulate and evaluate the stability profile of an anti-obesity nutraceutical combination in different dosage forms. Methods: Active and inactive ingredients were formulated into pharmaceutical dosage forms. The quality parameters of the dosage forms were determined, followed by accelerated stability testing (40±2 °C and 75±5% Relative Humidity (RH)) for 180 d was completed to evaluate their physical, chemical and microbiological attributes throughout the storage period. Results: Pre-formulation parameters of the powder blend of active and inactive ingredients for each dosage form showed a satisfactory flowability with Hausner's ratio falling between 1.16 and 1.18, average angle of repose between 22.29° and 22.90° and acceptable compressibility with Carr’s index below 25%. Tablets assessments were acceptable with a mean friability value of 0.21±0.03%, hardness of 4.12±0.09 kg/cm2. The average disintegration time of 5 min 10 sec for tablets and 4 min and 30 sec for capsules. The accelerated stability study revealed that tablet dosage forms are stable for longer period that can reach up to 180 d (24 mo real-time), while sachets and capsules are stable for a period of 135 d (18 mo real-time). Conclusion: The anti-obesity blend of White Kidney Bean Extract (WKBE), Propolis Ethanolic Extract (PEE) and CrPic3 can be successfully formulated in acceptable and convenient dosage forms that can be stable for 18-24 mo.

DESIGN, DEVELOPMENT AND IMPROVEMENT OF AN EMULGEL CONTAINING SILVER NANOPARTICLES AND VITAMIN D-3 FOR ITS POTENTIAL TO ACCELERATE THE HEALING OF WOUND

Objective: The aim of this research work was to prepare a topical emulgel based dosage form incorporated with vitamin D-3 and silver nanoparticles to reduce the wound healing time in any kind of wound. Methods: Central Composite Design (CCD) was applied for the optimization of emulgel by using Design expert software. Three responses (pH, viscosity, and in vitro drug release) and two factors (Carbopol concentration and stirring duration) were chosen, and Statistical Analysis of Variance (ANOVA) revealed that all the factors were significantly affecting the responses. Silver Nanoparticles (SNPs) was prepared with Green Tea Extract (GTE) and evaluated for particle size, Poly Dispersity Index (PDI), zeta potential and Fourier Transform Infra-red (FTIR) spectroscopy and revealed that SNPs of desired range and stability have been synthesized. Here excision wound model was used to evaluate the wound healing activity of formulation in vivo. Results: Maximum in vitro release 88.2±2.1 has shown by the optimized formulation F13, pH and viscosity were also found in optimum range i.e., 6.2±0.4 and 1672±33 respectively, followed by Korsmeyer and Peppas model. Total eight groups were designed for animal study and silver sulphadiazine was used as marketed formulation. F13 formulation was further evaluated for in vivo data, it was revealed that emulgel loaded with high dose of vitamin D-3 along with silver nanoparticles has shown 100.5±1.7% wound contraction, while marketed formulation has shown 103.7±1.1% wound contraction, which was much similar with test formulation. Cytotoxic cell study was done using assay on chicken egg, formulation has not shown any cytotoxic behaviour like haemolysis and cell damage on chick embryo’s blood vessels. Accelerated stability study of the optimized formulation was also performed to check whether the formulation was stable or not and it was revealed that optimized formulation was found stable for the period of six months. Conclusion: It was revealed that emulgel loaded with high dose of vitamin D-3 and SNPs found suitable to accelerate wound healing and showed almost similar response in wound contraction on comparison with marketed formulation. This emulgel promised to controlled the delivery of the drug for the longer duration.

Accelerated stability modeling of recrystallization from amorphous solid Dispersions: A Griseofulvin/HPMC-AS case study

Amorphous solid dispersions (ASDs) represent an important approach for enhancing oral bioavailability for poorly water soluble compounds; however, assuring that these ASDs do not recrystallize to a significant extent during storage can be time-consuming. Therefore, various efforts have been undertaken to predict ASD crystallization levels with kinetic models. However, only limited success has been achieved due to limits on crystal content quantification methods and the complexity of crystallization kinetics. To increase the prediction accuracy, the accelerated stability assessment program (ASAP), employing isoconversion (time to hit a specification limit) and a modified Arrhenius approach, are employed here for predictive shelf-life modeling. In the current study, a model ASD was prepared by spray drying griseofulvin and HPMC-AS-LF. This ASD was stressed under a designed combinations of temperature, relative humidity and time with the conditions set to ensure stressing was carried out below the glass transition temperature (Tg) of the ASD. Crystal content quantification method by X-ray powder diffraction (XRPD) with sufficient sensitivity was developed and employed for stressed ASD. Crystallization modeling of the griseofulvin ASD using ASAPprime® demonstrated good agreement with long-term (40 °C/75 %RH) crystallinity levels and support the use of this type of accelerated stability studies for further improving ASD shelf-life prediction accuracy.

Development and Evaluation of Polyherbal Hair Dye Formulation

Background and objectives: Hair care products including hair dye play an important role in the maintenance and enhancement of appearance and overall wellbeing of the hair. Most of the hair dye available in the market contains harmful chemicals that may cause allergic reactions or irritation of the scalp. The objective of this study focuses on the formulation and evaluation of hair dye as creams and gels with different shades by using herbs. Methodology: The collected plants were authenticated, and shade dried. Then, extractions were done using water, ethanol, and methanol. Preliminary testing was conducted to obtain burgundy, brown and black by manipulating the ratios. Later, almond oil, coconut oil, beeswax and Carbopol-934 gel were added to ease the penetration. Finally, accelerated stability studies were done to check the physical and microbial stability of the product. Results: Eight different shades of hair dye were formulated in gel and cream form. Among them gel formulation F5 and F6 as well as the cream formulations F1, F2, F3, F4, F7 and F8 demonstrated good staining and better colour intensity. The accelerated stability studies of F1 to F8 revealed that there is no change in the physical evaluation and no evidence of microbial contamination. Conclusion: The output of this research is suitable for all races and age group because it is not a permanent hair dye that might have a restriction for some groups of races. As such, this hair dye is fully formulated with natural sources by considering in the reduction of severe side effects to the consumers.

On the Feasibility of Rugose Lipid Microparticles in Pressurized Metered Dose Inhalers with Established and New Propellants.

Pressurized metered dose inhalers (pMDIs) require optimized formulations to provide stable, consistent lung delivery. This study investigates the feasibility of novel rugose lipid particles (RLPs) as potential drug carriers in pMDI formulations. The physical stability of RLPs was assessed in three different propellants: the established HFA-134a and HFA-227ea and the new low global-warming-potential (GWP) propellant HFO-1234ze. A feedstock containing DSPC and calcium chloride was prepared without pore forming agent to spray dry two RLP batches at inlet temperatures of 55 °C (RLP55) and 75 °C (RLP75). RLPs performance in pMDI formulations was compared to two reference samples that exhibit significantly different performance when suspended in propellants: well-established engineered porous particles and particles containing 80% trehalose and 20% leucine (80T20L). An accelerated stability study at 40°C and relative humidity of 7% ± 5% was conducted over 3months. At different time points, a shadowgraphic imaging technique was used to evaluate the colloidal stability of particles in pMDIs. Field emission electron microscopy with energy dispersive X-ray spectroscopy was used to evaluate the morphology and elemental composition of particles extracted from the pMDIs. After 2weeks, all 80T20L formulations rapidly aggregated upon agitation and exhibited significantly inferior colloidal stability compared to the other samples. In comparison, both the RLP55 and RLP75 formulations, regardless of the propellant used, retained their rugose structure and demonstrated excellent suspension stability comparable with the engineered porous particles. The studied RLPs demonstrate great potential for use in pMDI formulations with HFA propellants and the next-generation low-GWP propellant HFO-1234ze.

Gum odina prebiotic induced gut modulation for the treatment of colon cancer on Swiss albino mice: By using capecitabine loaded biopolymeric microsphere

A complex illness with a current global hazard, colon cancer has many different manifestations. The efficacy of colon cancer therapy can be affected by the bacteria in the digestive tract. It is hypothesised that novel prebiotics like Gum Odina is emerging as preventative therapy to fight chronic gut illnesses by gut microbiota modulatory therapy when compared to traditional intervention. The first-line chemotherapy drug for colon cancer, capecitabine, lacks a carrier that can extend its half-life. Here, we use the prebiotic gum odina – sodium alginate conjugate to create a capecitabine loaded biopolymeric microspheres, which were previously established as excellent tools for colon cancer therapy. The accelerated stability study exhibited that the alteration in physicochemical properties was found to be negligible. When administered orally to mice with colon cancer, capecitabine raises intra-tumoral capecitabine concentration and slows drug elimination in the blood. Optimized formulation improves anti-tumor immunity over free capecitabine and decrease the tumor volume from 8 ± 6.59 mm3 to 5.21 ± 2.79 mm3. This prebiotics based microsphere combine's gut microbiota manipulation with chemotherapy to offer a potentially effective colon cancer treatment.

Mucoadhesive Buccal Tablet Formulation of Azithromycin dihydrate for treatment of Upper Respiratory Tract Infection

The buccal drug delivery system is a versatile delivery system which can be designed for local or systemic effect. The objective of the study was to developed patient complacent tablet which can give sustain release of antibacterial agent for relief of upper respiratory tract infection. Azithromycin dihydrate is a semi-synthetic macrolide antibiotic widely used to prevent bacterial infections in the upper respiratory tract. The mucoadhesive buccal tablets of azithromycin dihydrate were formulated by varying concentrations of polymers (natural and synthetic), glidant and other excipients. The drug-excipient compatibility studies were carried out through DSC and FTIR studies. The selected excipients were found to be compatible. Further the dry blend of drug-excipients was evaluated for pre-compression properties. The prepared tablets were evaluated as per the general monograph for tablets of IP. The studies were also carried out to evaluate sustained release of the drug and mucoadhesivity of the tablets. A 23 level (2 level and 3 factors) factorial design was navigated to study the effect of natural, synthetic polymers and the glidant on mucoadhesive strength and percentage cumulative drug release at 8 hours. The responsive variables were analysed using ANOVA by Design-Expert version 12.0. It was concluded that these excipients significantly affected the response variables. The optimized tablet formulation was found to have an adequate mucoadhesion and a cumulative percentage release. The final product was performed for accelerated stability studies, optimized formulation was found to be stable at room temperature and accelerated temperature for three months.

FORMULATION, CHARACTERIZATION AND OPTIMIZATION OF FOLIC ACID-TAILORED DAIDZEIN SOLID LIPID NANOPARTICLES FOR THE IMPROVED CYTOTOXICITY AGAINST COLON CANCER CELLS

Objective: The study aims to formulate and optimize daidzein-conjugated folic acid solid lipid nanoparticles (DZN-FA SLNs) to improve bioavailability and target site specificity for the treatment of colon cancer, a significant global health concern associated with high morbidity and mortality. Methods: DZN-FA SLNs were prepared using the microemulsion method. They were prepared and optimized using design expert software. Physicochemical characterization like differential light scattering (DLS), Fourier transformed infrared spectroscopy (FTIR), scanning electron microscope (SEM), In vitro drug release and In vitro cell line studies and accelerated stability studies were carried out in the optimized batch formulation. Results: The results indicated that particle size for optimized DZN-FA SLNs was in the range of 212 to 620 nm, zeta potential of-20 mV, drug entrapment efficiency of 72%. In vitro drug release for the prepared formulation showed 53% over 48 h. Conclusion: The optimized DZN-FA SLNs could aid in a better formulation targeting colon cancer cells, thereby reducing systemic effects. The optimized DZN-FA SLNs have demonstrated excellent inhibitory properties on Caco-2 cells, with an IC50 value of 10 µg/ml, offering a promising innovation in cancer treatment by providing targeted and effective therapy for colon cancer while minimizing the impact on normal cells.

Development of In-situ Gel of Bupropion Hydrochloride-loaded Chitosan Nanoparticles using an Inotropic Gelation Method for Smoking Cessation via Nose to Brain: In-vitro and Ex-vivo Characterization and Evaluation

Introduction: Tobacco use is the leading preventable cause of various diseases, disabili-ties, and death. It is estimated that 480000 deaths annually are attributed to cigarette smoking, in-cluding secondhand smoke exposure. The treatment of brain disorders is particularly challenging due to the presence of a variety of formidable obstacles to delivering drugs selectively and effec-tively to the brain. The blood-brain barrier (BBB) and first-pass metabolism constitute the major obstacle to the uptake of drugs into the brain following systemic administration. Intranasal delivery offers a non-invasive and convenient method to bypass the BBB and avoid first-pass metabolism, which leads to the delivery of therapeutics directly to the brain. Objective: The objective of this study was to develop an In-situ gel of Bupropion Hydrochloride-loaded chitosan nanoparticles using the inotropic gelation method for Smoking Cessation via the nose to the brain to improve the bioavailability of Bupropion Hydrochloride, avoiding first-pass me-tabolism and bypassing Blood Brain Barrier. Methods: Fourier transform infrared spectroscopy (FTIR) was used to determine the identity and purity of the drug. A UV Spectrophotometer was employed in the analytical procedure. Chitosan nanoparticles loaded with bupropion HCl were made using the ionic gelation method, and then the optimized batch was made using simulated in-situ gelation. Utilizing Central composite design, op-timization was done by Design Expert-13. Evaluation of polymeric nanoparticles was performed by measuring their particle size, PDI, and entrapment efficiency. Additionally, they were tested for drug release in vitro. The final nanoparticles were subsequently tested for gelation using nasal simulation fluid, and an ex vivo investigation was also conducted. An ion-sensitive polymer gellan gum was used as a gelling agent, which formed an immediate gel and remained for an extended period. The finished formulation was also subjected to several characteri-zations, including TEM and FTIR. Results: The developed formulation was stable and showed enhanced contact time in the nasal mu-cosa, minimizing the frequency of administration. In-vitro studies through Franz diffusion cell and Ex-vivo studies on sheep nasal mucosa showed good results. In the Histopathological study, the op-timized batch was found to be safe and stable in an accelerated stability study for one month. Conclusion: Bupropion HCl-loaded chitosan nanoparticles In-situ gel proved to be suitable for the administration of Bupropion HCl through the nasal route. The ease of administration coupled with less frequent administration enhanced patient compliance. The formulation was found to be liquid at the formulated condition and formed gel in the presence of ions present in the nasal mucosa. The gel formed in situ showed sustained drug release. The formulations were less viscous before instilla-tion and formed a strong gel after instilling in the nasal cavity.

Optimization and characterization of xanthan gum based multiparticulate formulation for colon targeting

To optimize and characterize xanthan gum multi-particulate formulation for colon targeting, which increases the residence time at the absorbing surface of the colon. Xanthan gum was dispersed in cold water containing drug and was permitted to expand for 2 ​h. Sodium alginate was blended well in 10 ​ml of water. Xanthan gum solution containing the drug was added to sodium alginate solution and 0.3 ​ml of glutaraldehyde was added to the dispersion, with constant stirring. Then, polymer-drug solution was added dropwise into 5% w/v calcium chloride solution with continuous stirring, producing microspheres filtered by Whatman filter paper and dried at 30 ​°C–40 ​°C. Microspheres were performed by chemical cross-linking with glutaraldehyde, which increased the maximum drug entrapment efficiency up to 73.63 ​± ​0.65% with an increasing concentration of xanthan gum polymer 0.7% w/v for the optimized F6 batch. Better results were found by increasing the polymer concentration along with the glutaraldehyde concentration. The kinetics of drug release for the F6 batch was considered as an optimized batch because the regression value was found to be 0.997 in the peppas model. The accelerated stability study on the optimized F6 batch performed to learn whether the drug has any change during its period of usability. The polysaccharide remains intact in the stomach and intestine and the drug was released in the colon with low toxicity and biodegradability. The present studies showed that optimizing and characterizing xanthan gum multi-particulate formulation for colon targeting gives metronidazole the most effective and controlled delivery.