Accelerated Stability Studies Research Articles

Formulation and evaluation of oral dispersible tablet of nimesulide by direct compression method

Based on Biopharmaceutics Classification System (BCS), nimesulide is a class II drug, characterized by low solubility and high permeability. Thus, its dissolution represents a limiting step in the drug absorption process which directly affects the bioavailability of the drug. Oral Dispersible tablets (ODTs) of nimesulide overcome the problem related to dissolution by enhancing the rate of dissolution by decreasing the disintegration time and making it easy to administer to patients who refuse to swallow a tablet. In the present study, different formulations of nimesulide were prepared to vary the concentration of superdisintegrants: crospovidone, croscarmellose sodium, sodium starch glycolate along with other excipients: PVP K-30, Aerosil, Mannitol, and Magnesium stearate by direct compression method. Precompression and post-compression parameters were evaluated and also the effect of different concentrations of superdisintegrants on the release profile of Nimesulide ODT was studied. The final data revealed that a combination of 10% crospovidone and 8.33% SSG i.e. formulation B4 was found best combination with the lowest dispersion time of 40 seconds, lowest disintegration time of 19.16 seconds, and lowest wetting time of 15 seconds as compared to other formulations. All other studied parameters were found to be satisfactory for all ODT formulations for Nimesulide. It was concluded that Nimesulide can be successfully formulated as oral dispersible tablets using various superdisintegrants in different concentrations by direct compression method. The optimized batch can be subjected to real-time and accelerated stability studies to determine the shelf life for commercial use.

Potential use of red hibiscus flower extract for the production of spray-chilled microparticles: Characterization, stability, and bioaccessibility in vitro of anthocyanins

Microparticles (MLP) containing red hibiscus flower (Hibiscus rosa-sinensis) anthocyanins were produced by spray chilling, and characterized for physicochemical parameters, accelerated stability, and gastrointestinal release profile. Fully hydrogenated palm oil and cocoa butter were used as wall materials, at a lipid blend to hibiscus extract ratio of 70:30 (w/w). The lipid blends containing fully hydrogenated palm oil (FHPO) and cocoa butter (CB) were produced by ultrasound-assisted technique in the following FHPO to CB ratios: 100:0 (Control), 75:25, 50:50, 60:40, and 40:60. Increasing the cocoa butter content reduced the melting temperature and increased the unstable polymorphic behavior of the microparticles, resulting in amorphous characteristics. The microparticles exhibited higher viscosity, more agglomerates, and holes on the surface, and greater diameters. Characteristic peaks corresponding to the hibiscus extract were observed in the infrared spectra of the spray-chilled microparticles, indicating that the microencapsulation did not affect the anthocyanins. The antioxidant capacity of the red hibiscus anthocyanins ranged from 75 % to 79 %, with the best result observed for the treatment MLP_75:25. Higher antioxidant activities were observed for the lipid blends containing lower cocoa butter concentrations. Concerning the release profile of anthocyanins, the simulated GI digestion in vitro showed reduced release in the gastric tract and more intense release in the intestinal tract for an effective absorption of the antioxidant compounds in the small intestine. Furthermore, the treatment MLP_75:25 showed the highest encapsulation retention and lower total color difference in the accelerated stability study. Overall, the microparticles from all treatments were light-sensitive and thermosensitive at 35 °C. Thus, it is recommended to store the particles in a dark environment at temperatures below 35 °C for an effective use of the microparticles as natural food colorants.

B-100 Hbsag Performance Improvement of Novel MASTM Infectious Controls for Serology Diagnostic Tests

Abstract Background Hepatitis B is a liver infection caused by the Hepatitis B virus. While preventable by vaccination, Hepatitis B remains prevalent across the globe. While prevalence is low in many areas of the world, there are still regions in which the prevalence is considered to be high. Hepatitis B surface antigen (HBsAg) can be one of the first indicators of Hepatitis B infection, and it is a commonly screened diagnostic test to determine if a patient is immune, susceptible, or has acute or chronic HBV infection. While HBsAg is a critical marker in diagnosing a patient, it presents unique challenges. The Thermo Scientific™ MAS™ Omni™ Infectious BSI Positive Control Panel* is a multi-constituent IVD control containing anti-HIV-1/2, anti-HBc, anti-HCV, and anti-HTLV I/II antibodies, as well as Hepatitis B surface antigen (HBsAg) in a human plasma-based matrix. Development and Stability Studies were conducted to evaluate and ensure optimal analyte performance throughout the shelf-life duration. As this is a multi-constituent control, the HBsAg challenges must be adequately addressed to ensure the integrity and reliability of the results of all analytes. Two specific areas of focus are HBsAg instability at increased temperature and HBsAg-Fibrinogen interaction in plasma products. We report here the continued development and assessment of HBsAg in the MAS™ Omni Infectious Controls family. Methods The BSI Positive Control Panel was evaluated with IVD assays to assess Shelf-Life and demonstrate the effect of elevated temperature and fibrinogen on HBsAg. Shelf life of the products was determined by real-time, accelerated, open vial, and in-use stability monitoring. Additionally, open-vial stability monitoring demonstrates the relationship between HBsAg and fibrinogen within the control products. Between Month 0 and 12, samples were run neat without processing. At Month 12, samples were centrifuged to verify the validity of the open-vial stability claim. Results The evaluation of the BSI Positive Control Panel demonstrates the effects of temperature and fibrinogen on HBsAg. The Real-Time and Accelerated stability studies combine to demonstrate the effect of elevated temperatures on HBsAg within the multi-analyte control. The Open-Vial stability studies completed at 0 and 12 months combine to demonstrate the effect of fibrinogen on HBsAg within the multi-analyte control. Conclusions The MAS™ Omni Infectious control products will perform optimally provided the proper sample processing and storage conditions are implemented. Improper storage at elevated temperatures will result in degradation at an increased rate for the HBsAg present in the sample. Additionally, it is imperative that the proper raw materials are chosen in the production of the multi-analyte controls. When using plasma products, it is best to use defibrinated plasma. For extra precaution, raw material should be centrifuged and filtered prior to production to avoid degradation due to fibrinogen. Reliable, high-quality controls are vital in ensuring that clinical diagnostic assays are functioning properly. *Availability of product in each country depends on local regulatory marketing authorization status

Unified chromatography in drug development: Exploiting chaotropic/kosmotropic salts for an accelerated method development

Recent trends in supercritical fluid chromatography (SFC) introduced an innovative gradient profile called Unified Chromatography (UC), which pushes the amount of liquid modifier up to 80–100 % of the total mobile phase composition. These new conditions allow the full transition from a supercritical to a liquid state, unifying the benefits of both SFC and liquid chromatography. However, to facilitate the use of UC for industrial drug development, a stronger effort is needed to streamline and simplify its method development and optimization. In this work, a quick and novel method development procedure for UC is introduced, enabled by the first-time use of novel additives in SFC/UC that exploit chaotropic/kosmotropic properties. A comprehensive view on some fundamental properties, such as the amount of liquid modifier blended with supercritical CO2 (scCO2) and the percentage of water added in the mobile phase is given, to clarify the benefits of using either a chaotropic salt (NaClO4), kosmotropic (HCOONa) or salt with mixed properties (NaOMs – sodium methanesulfonate). With this expanded knowledge, challenging separations of nucleosides, nucleotide, indoles, triazoles and related derivates have been accomplished with UC. Finally, we provide an example of UC delivering a faster and better method for an AbbVie pipeline compound under accelerated stability study. The combined use of scCO2-based chromatography and the novel additive NaClO4 ensures the retention and elution of all degradation species generated at different conditions, where RP-HPLC failed to provide satisfactory performance.

Preparation, statistical optimization, in-vitro evaluation and characterization of solid lipid nanoparticles of an anti-retroviral drug Nevirapine

Nevirapine-loaded solid lipid Nanoparticles (SLNs) were manufactured using lipid and emulsifying agent by hot homogenization method. The goal of research was to formulating a SLN system to target the HIV reservoir which is mostly found in the lymphatic system and to conquer the obstacle of drug itself. Also, nearly 50% of antiviral drugs fall within BCS class 2, which have low solubility. 44% antiviral drugs belongs to BCS class 3 have inadequate permeability and 6% belongs to class 4 with inadequate solubility and inadequate permeability. Depending on the NVP solubility and stable formulation, stearic acid as a lipid and poloxamer 188 and tween 80 as an emulsifying agent were chosen and SLNs were manufactured with the help of hot homogenization method. Optimization of independent variables such as lipid concentration, emulsifying agent concentration and no. homogenization cycle was carried. The effect of independent variables on the dependent variables i.e. particle size and entrapment efficiency was studied. Optimized formulation which was lyophilized (L-SLN) and this L-SLN additionally characterized using DSC, SEM and XRD analysis. Also, in-vitro drug release of optimized batch studied in 0.04 M Sodium phosphate buffer pH 6.8 containing 2% SLS, demonstrated 41.83% release at the end of 24th hr. Absence of low intensity in XRD indicated the presence of amorphous SLNs. SEM showed the morphology of SLNs. No prominent changes observed in the accelerated stability studies.

A Study on the Stability and Antimicrobial Efficacy of a Newly Modeled Teat Dip Solution Containing Chlorhexidine.

Despite much focus on mastitis as an endemic disease, clinical and subclinical mastitis remains an important problem for many herds. Reducing the usage of antibiotics for mastitis treatment allows the risks to be minimized related to the development of antimicrobial resistance and the excretion of antibiotics into the environment. The aim of the study was to determine the physico-chemical properties, stability and antimicrobial effect of a newly formulated biocide for post-milking udder hygiene containing a thickener made from hydroxypropyl guar gum, an antiseptic chlorhexidine digluconate and teat skin-friendly components including glycerol, Mentha Arvensis herbal oil and Aesculus hippocastanum extract. Hydroxypropyl guar gum was used as a thickener to provide the physical parameters and to retain the viscosity at 1438 mPa.s. The physical and chemical properties of the product, including the 12-month stability, were tested in long-term and accelerated stability studies. The product was effective against the primary mastitis pathogens, including Staphylococcus aureus, Streptococcus uberis, Escherichia coli, Candida albicans and Aspergillus niger.

Development and In Vitro-In Vivo Correlation Evaluation of IMM-H014 Extended-Release Tablets for the Treatment of Fatty Liver Disease.

This study aimed to develop extended-release tablets containing 25 mg IMM-H014, an original drug formulated by a direct powder pressing method based on pharmaceutical-grade hydrophilic matrix polymers such as hydroxypropyl methylcellulose, to establish an in vitro-in vivo correlation (IVIVC) to predict bioavailability. The tablets' mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single-factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were determined in five dissolution media, in which the drug released from the hydrophilic tablets followed the Ritger-Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate-buffered saline medium (pH 7.5) for a further 24 h. Accelerated stability studies (40 °C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmacokinetics study in beagle dogs showed that compared to the IMM-H014 immediate release preparation, the maximum plasma concentration of the extended-release (ER) preparation was significantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on the area under curve, indicating that the optimal formulation has an obvious ER profile, and a good IVIVC was established, which could be used to predict in vivo pharmacokinetics based on the formulation composition.

Flavour enhancement strategy for herbal beverages and kinetic modelling of their antioxidant and sensory properties in accelerated storage conditions

Herbal infusions and beverages are part of culinary practices and home remedies of many ethnic groups globally. Centella asiatica, Enhydra fluctuans, Eryngium foetidum and Marsilea minuta are four important herbs that used to be consumed in different East and South Asian countries due to their health benefit. The herbs are not very acceptable by the millennials due to their off flavour and bitterness. In this study, Centella asiaitica was found to be an appropriate candidate for herbal beverages among the said four herbs. A Centella based beverage was developed that can deliver high antioxidant activity together with acceptable sensory properties. Out of the two common methods of herbal beverage preparation (i.e., infusion and decoction), infused beverage was adopted owing to its better sensory acceptance. The grassy flavour of the Centella infused beverage was masked with Khasi mandarin (Citrus reticulata) peel powder (90% Centella asiatica powder with 10% Khasi mandarin peel powder). Further, the accelerated storage study revealed that Centella asiatica powder was stable during ambient storage conditions (RH 61% and 32 °C), whereas the sensory acceptability, physicochemical properties, and the antioxidant potential of the powder degraded significantly at higher temperature (45 °C and RH 82%) especially with UV exposure. The impact of storage conditions on the most critical quality parameters i.e., colour, pH, and antioxidant capacity was estimated with a first-order degradation model. All the antioxidant capacity values showed different intrinsic rates of decay and the half-life of lipid peroxidation values was shortest among the four antioxidant capacity values. This work reports a unique accelerated stability study protocol to screen the packaging and storage conditions for herbal powders. Additionally, the results suggested, Citrus peel blending is a novel approach to make herbal beverages more acceptable to consumers due to better sensory perception and enhanced stability of the herbal powder.

MAP-box: a novel, low-cost and easy-to-fabricate 3D-printed box for the storage and transportation of dissolving microneedle array patches

Research on the use of microarray patches (MAPs) has progressed at an unprecedented rate over the years, leading to the development of many novel drug delivery systems. As the technology approaches patients, there are several key aspects that ought to be addressed in order to facilitate the smooth translation of MAPs from bench to bedside. One integral factor includes the choice of devices and packaging for the storage of MAPs. In the current work, a slide-and-seal box, MAP-box, was developed for the storage of dissolving MAPs, using fused-deposition modelling. The device has been designed to act as a pill-box for MAPs not only to provide protection for MAPs from the environment, but also to improve patient’s adherence to treatment. The overall design of the MAP-box was simple, yet offers the capability of sealing and protecting dissolving MAPs up to 30 days. Donepezil HCl was formulated into a dissolvable MAP, which was used to treat dementia related to Alzheimer’s disease. This compound was used as a model formulation to evaluate the utility of the 3D printed MAP-box when placed under three storage conditions: 5 °C and ambient humidity, 25 °C and 65% relative humidity and 40 °C and 75% relative humidity. It was shown that the slide-and-seal box was able to confer protection to MAPs for up to 30 days under accelerated stability study conditions as the drug loading, mechanical properties and insertion properties of MAPs remained unaffected when compared to the unpackaged MAPs stored under these same parameters. These preliminary data provide evidence that the MAP-box prototype may be of great utility for the storage of single or multiple MAPs. Nevertheless, future work will be needed to evaluate their patient usability and its application to different types of MAP systems to fully validate the overall robustness of the prototype.Graphical

Devitrification of lyoprotectants: A critical determinant for bacteriophages inactivation in freeze-drying and storage

Bacteriophages as promising natural antibacterial additives are widely used in food processing and storage. Although freeze-drying is an economical and efficient way to preserve phages, so far there is limited data for phage freeze-drying and key factors that inactivate phages during freeze-drying and storage remain unknown. Here we systemically compared different types of saccharides/polyols (dextran 5000, glucose, sucrose, trehalose, mannitol, and xylitol) as lyoprotectants and their potential ratios for phage freeze-drying. The pH and osmotic pressure tolerance of bacteriophages were determined and all lyoprotectant solutions were within the tolerance range of phages. Combined with thermodynamic data, it was found that only completely vitrified formulations (glucose, sucrose, and trehalose) could preserve phages during freeze-drying. Selected freeze-dried phages were further arranged for an accelerated stability study. Most formulations stored at higher temperatures (≥25 ℃) presented devitrification, resulting in a significant drop in phage titer. 10% (w/v) of sucrose was recommended as the best formulation for freeze-dried phage storage with less devitrification and a better fitting coefficient (R2 = 0.9592) to the Arrhenius equation, predictively reaching shelf-time as 1093.3 days at 4 ℃ storage. These findings implied that the devitrification of lyoprotectants was the critical determinant for bacteriophage inactivation both in freeze-drying and storage.

DEVELOPMENT AND CHARACTERIZATION OF PALONOSETRON HYDROCHLORIDE JELLIES

Aim and objective: Dysphagia is one of the most common diseases mainly in geriatric and podiatric populations. As swallowing is the main difficulty in dysphagic patients, in that situation medicated jelly preparations are the best alternative to conventional doses forms (tablets and capsule doses form). This research article is aimed at the formulation and evaluation of Palonosetron hydrochloride oral jelly to avoid swallowing related issues in paediatric and geriatric patients and to improve its bioavailability. Methods: Two methods i.e., congealing and heating were chosen to prepare sucrose-based jellies. All prepared formulation were evaluated on different parameters like physical appearance, drug content, pH and dissolution study, stability study etc. Results: All formulation was found free from any type of gritty particles. Out of all formulations MJ1 was found best formulation on the basis of drug release profile i.e., 79.22% within 30 mins. Accelerated stability studies also confirmed that MJ1 and MJ2 are the best formulations. Conclusion: This study concludes that Palonosetron hydrochloride can be delivered successfully by the means of jellies to avoid first pass metabolism. Peer Review History: Received: 4 March 2023; Revised: 26 April; Accepted: 20 June 2023, Available online: 15 July 2023 Academic Editor: Dr. Emmanuel O. Olorunsola, Department of Pharmaceutics & Pharmaceutical Technology, University of Uyo, Nigeria, olorunsolaeo@yahoo.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Rola Jadallah, Arab American University, Palestine, rola@aauj.edu Dr. Ogbonna B. Onyebuchi, Nnamdi Azikiwe University, Awka, Nigeria, summitpharm@yahoo.com

Identification of Quercetin, Kaempferol and Luteolin from Methanolic Extract of <i>Corchorus depressus</i> and its Pre-Clinical Wound Healing

Corchorus depressus Linn. (Tiliaceae) has been extensively utilized in Odisha, India, and is considered sacred and religious in addition to being used in Pakistan, Baluchistan, and Sind for ethnopharmacological purposes. Ethno-pharmacological claims and lack of sufficient scientific data with respect to the wound-healing activity of the plant encouraged us to the preparation of herbal formulation and its evaluation against wound-healing models with the identification of the phytoconstituents present in the plant extract. The physiochemical properties of the plant like ash value, the preliminary phytochemical screening, the HPLC, HPTLC, FTIR analysis, and the dermal toxicity of the methanolic extract were carried out using standard methods. A stability study was conducted on the prepared ointment formulations. With the help of in vivo excision, incision, dead-space wound, mice-burn model, and along with in vitro stimulation of Interleukin-10 models, the wound healing potential was evaluated. The granulation tissue was collected for nitric oxide estimation and histopathological analysis. The tensile strength of the granuloma tissue and hydroxyproline content were estimated using standard methods. The methanolic extract ointment resulted in a steady contraction of wounds with time and caused significant inhibition in the level of nitric oxide in the scar tissue and aggregation of macrophages in histological examination. The incision model showed a significant (381.33±4.58, p<0.05) increase in the tensile strength of granuloma tissue when compared to the control (156.5±5.75). The dead space wound model demonstrated that the plant extract significantly increased (75.43±2.97, p<0.001) hydroxyproline content against the control. Methanolic extract ointment caused significant wound healing and reduced epithelialization time in the mice burn model from the 12th day till the 24th day as compared to the negative control. Observations of hematological and serum biochemical changes in the dermal toxicity study suggested that the herbal extracts are safe for use topically. In the accelerated stability study, there were no marks of physical instability in the prepared ointment. IR spectral analysis was successfully used to detect flavanones like Luteolin and flavonol such as Quercetin and Kaempferol in methanolic extract. The present findings provide scientific evidence that the plant Corchorus depressus Linn. (Tiliaceae) displayed wound healing activity, corroborating its traditional use by the Tribals of Odisha and the Indian system of medicine.

Formulation Intervention to Overcome Decreased Kinetic Solubility of a Low Tg Amorphous Drug.

This technical note investigated the loss of dissolution rate during accelerated stability studies with a dry blend capsule formulation containing an amorphous salt of drug NVS-1 (Tg 76°C). After 6 m at 40°C/75%RH, dissolution of NVS-1 was ≤40% of initial value. Scanning electron microscope characterization of the undissolved capsule contents from samples stored at 50°C/75%RH for 3 weeks showed agglomeration with a distinct "melt and fuse" morphology of particles. At elevated temperature and humidity conditions, undesired sintering among the amorphous drug particles was observed. Humidity plasticizes the drug as the stability temperature (T) gets closer to the glass transition temperature (Tg) of the amorphous salt (i.e., smaller Tg-T); a decreased viscosity favors viscoplastic deformation and sintering of drug particles. When moisture is adsorbed onto agglomerated drug particles, partial dissolution of the drug forms a viscous surface layer, further reducing the rate of dissolution media penetration into the bulk solid, hence the slower dissolution rate. Formulation intervention focused on the use of L-HPC and fumed silica as disintegrant and glidant and the removal of the hygroscopic crospovidone. Reformulation improved dissolution performance at short-term accelerated stability conditions of 50°C (± 75%RH); however, sintering to a lesser extent was still observed at high humidity, impacting the dissolution rate. We infer reducing the impact of moisture at high humidity conditions in a formulation with a 34% drug load is challenging. Future formulation efforts will focus on the addition of water scavengers, reducing drug load by ~50% to physically separate drug particles by water-insoluble excipients, and optimizing disintegrant levels.

Development of solid lipid nanoparticles of diacerein in a stable oral liquid dosage form using a central composite design

Diacerein (DCN) is used mainly to treat degenerative diseases, such as osteoarthritis. DCN is marketed commercially in solid dosage forms. Liquid formulations of diacerein (DCN) have been hindered by its poor chemical stability in aqueous media. This work aims to develop a novel, stable, oral, liquid preparation of DCN having a concentration of 50 mg/5 ml. Solid lipid nanoparticles (SLNs) of DCN were prepared using cetyl alcohol as the lipid matrix and Tween 80® as a surfactant. A quality-by-design approach was utilized to optimize DCN-SLNs. The optimum DCN-SLNs were dispersed in a structured vehicle to formulate the liquid dosage form. This liquid preparation was subjected to accelerated stability studies at 40 °C and 75% RH for 6 months. The potential of the liquid preparation to minimize the diarrheal effect of DCN was assessed. Optimum concentrations of cetyl alcohol (2%) and Tween 80® (0.9%) were chosen to obtain the desired characteristics of SLNs. Interestingly, we determined that 0.05% of citric acid was the maximum concentration that can be added to the liquid preparation of diacerein to modify its pH without compromising its stability. The results of the stability studies show that the liquid preparation was robust and it withstood storage conditions (40 °C, 75% RH) for 6 months. The encapsulation of diacerein helps to protect it from degradation and significantly reduced the occurrence of diarrhea as a side effect (p < 0.0001). Liquid preparations of DCN-SLNs can thus be marketed as a new dosage form.

Formulation and Evaluation of Gastro-retentive Drug Delivery System of Novel Famotidine Phospholipid Complex

Famotidine is an H2 receptor antagonist belonging to the BCS Class II, characterized by low solubility and limited oral bioavailability. The current study encompasses the formulation of novel famotidine phospholipid complex (FHC) with the aid of design of experiments (Central Composite Design) using solvent evaporation technique to overcome the disadvantages of Famotidine. To further enhance the physicochemical properties of FHC, it was incorporated into gastro-retentive floating tablets (GRDDS) using direct compression technique with sodium bicarbonate as a gas generating agent and its properties were compared to famotidine floating tablets. The pre-compression parameters, namely bulk density, tapped density, Hausner’s ratio, Carr’s compressibility index and angle of repose were evaluated. The flow properties of FHC granules were found to be better than the plain famotidine granules. The postcompression parameters, namely thickness, hardness, friability, weight variation, drug content and swelling index showed better results for FHC as compared to famotidine floating tablets. In-vitro buoyancy study indicated that the floating lag time for FHC tablets (110 ± 0.021 seconds) was higher than famotidine tablets (36 ± 0.033 seconds) owing to the higher molecular weight of phosphatidylcholine. But the total floating time for FHC tablets was found to be more than 18 hours and for famotidine tablets it was ~12 hours, indicating the improved residence time and buoyancy. The in-vitro dissolution study depicted that the cumulative release for FHC tablets (99.84 ± 0.058%) was enhanced 1.07 fold than Famotidine tablets (92.73 ± 0.028%) and 1.6 fold than marketed tablet, Famocid (62.24 ± 0.023%). When kinetic modeling was performed, famotidine tablet followed zero order kinetics, whereas FHC tablet followed Higuchi model indicating a modified and sustained release pattern. The statistical analysis for %cumulative release performed using ANOVA and Dunnett’s test showed the p-value to be below 0.05 (0.0043) indicating that the analysis model was significant. An accelerated stability study was performed for a period of 6 months at 25 ± 2°C; 60 ± 5% RH. FHC tablets showed a better stability profile than famotidine tablets. In conclusion, FHC gastro-retentive floating tablets showed improved flow properties, post compression properties, better drug content, improved in-vitro buoyancy and enhanced cumulative release and stability profile.

DESIGN, FORMULATION, AND IN-VITRO EVALUATION OF IMMEDIATE RELEASE TABLET OF ETORICOXIB USING QUALITY BY DESIGN (QbD) APPROACH

Introduction: The current research aimed to formulate and evaluate the immediate-release tablet of etoricoxib. Etoricoxib belongs to BCS class II drugs; hence the solubility was enhanced using different techniques, thus achieving the dissolution of the drug. The formulation with maximum solubility enhancement was selected as the final formulation for the preparation of immediate-release tablets. Material and Methods: These tablets were prepared using the wet granulation technique. Sodium starch glycolate was used as a super disintegrant, microcrystalline cellulose was used as a binder, and sodium bicarbonate was used as effervescent material for the preparation of an immediate-release tablet. Different trial batches were prepared and the formulations were optimized using design expert software. The optimized formulation was prepared and evaluated for different post-compression parameters. Results and Discussion: The disintegration time was found to be 2 minutes 16 seconds and the percent cumulative drug release was found to be 90.30%. The pharmacokinetic behavior of the drug was studied and first-order kinetics was found to be the best fit model for immediate-release tablets. The accelerated stability study for the immediate-release tablet was carried out at 40℃ ±75% RH and different parameters were evaluated and were found within specified limits. Conclusion: Thus immediate release tablets of etoricoxib were found to be a promising candidate for the treatment of acute pain or arthritis.

Formulation and Evaluation of Punica granatum L Seed Oil-loaded Cosmetic Cream: Its In-vitro Antioxidant Activity

Cosmetic creams for the antioxidant activity of Punica granutum L seed oil (PSO) were formulated in different concentrations of oil in F1 to F6 formulations of cosmetic creams and their physicochemical properties were evaluated. There are several different pharmacological actions attributed to P. granutum L seed oil. The prepared cream was evaluated its properties like pH, resistance to flow, spreadability size, and surface charge value, and ex-vivo release study were performed. All results are found within the limit and it complies with the specification as per requirements. Good in-vitro DPPH scavenging activity was observed from the optimized batches throughout the preparation. To determine the stability profile, cosmetic creams containing PSO (Batches F1 through F6) were exposed to a three-month accelerated stability study in accordance with ICH recommendations. From this study it was concluded that prepared batches used for various treatments of skin disorders.

A universal tool for stability predictions of biotherapeutics, vaccines and in vitro diagnostic products

It is of particular interest for biopharmaceutical companies developing and distributing fragile biomolecules to warrant the stability and activity of their products during long-term storage and shipment. In accordance with quality by design principles, advanced kinetic modeling (AKM) has been successfully used to predict long-term product shelf-life and relies on data from short-term accelerated stability studies that are used to generate Arrhenius-based kinetic models that can, in turn, be exploited for stability forecasts. The AKM methodology was evaluated through a cross-company perspective on stability modeling for key stability indicating attributes of different types of biotherapeutics, vaccines and biomolecules combined in in vitro diagnostic kits. It is demonstrated that stability predictions up to 3 years for products maintained under recommended storage conditions (2–8 °C) or for products that have experienced temperature excursions outside the cold-chain show excellent agreement with experimental real-time data, thus confirming AKM as a universal and reliable tool for stability predictions for a wide range of product types.

Shelf-Life Evaluation and Comparative High-Performance Thin-Layer Chromatography Profile of Amavatari rasa: A Preliminary Study

ABSTRACT Background: In addition to safety and efficacy data, it is important to establish quality parameters for all drugs, including shelf life. Shelf life is the length of time that a product may be stored without becoming unfit for use, consumption, or sale. Every product in this universe has a definite shelf life. In Ayurveda texts, shelf life is known as Saviryata avadhi that is defined as the time period during which the potency (Virya) of any drug remains unaffected. Amavatari Rasa (AR) is an important formulation being used in Ayurvedic therapeutics; however, its shelf life is not reported till date. Aims and Objectives: This study aimed to evaluate shelf life of AR through accelerated stability study. Materials and Methods: Accelerated stability study and comparative high-performance thin-layer chromatography (HPTLC) profile were done to evaluate the shelf life of the AR. The formulation was prepared by using authentic raw material in the departmental laboratory by the following classical guidelines. It was evaluated by analyzing changes in physicochemical profiles of the product after keeping it at specific temperature (40°C ± 2°C) and relative humidity (75% ± 5%). Analysis was carried out at the intervals of 0, 3, and 6 months. Average 10% degradation time was calculated and extrapolated to find the shelf life as per the ICH guidelines. Results and Conclusion: In the present study, shelf life of AR was found to be 48 months; similar Rf values obtained in HPTLC analysis of AR initially and after 6 months showed the minimum deterioration of the product.

Intranasal Delivery of Leuprolide Acetate Chitosan Nanoparticles for Treatment of Alzheimer’s Disease

Background: Alzheimer’s is one of the primary causes and the most prevalent form of age-related dementia worldwide. There is an urgent surge to find an effective treatment for AD due to its social implications on society. Aim: Present research work aims to develop Chitosan nanoparticles of leuprolide acetate for the treatment of Alzheimer’s disease by delivery through the intranasal route. Methods: Chitosan nanoparticles encapsulating leuprolide acetate were prepared using the ionic ge-lation method and optimized using a central composite design. The optimized nanoparticles were evaluated by DSC study, TEM analysis, release study of the drug in vitro and ex vivo, histopatholo-gy study, and accelerated stability study, In vivo kinetic and dynamic study. Results: The optimized formulation exhibited particle size of 254.3 ± 10.7 nm, % EE of 85.6 ± 0.8 %, and zeta potential of +18.0 ± 0.2 mv. The release of drug from optimized nanoparticles in vitro was in a sustained manner, with only 75.7 % drug released at 48 hours. Higher permeation of the drug from nanoparticles (Papp =5.44 ± 0.34 x 104) was observed in the diffusion study ex vivo. Sheep nasal toxicity and accelerated stability study proved the intranasal safety and stability of the developed formulation. The in vivo drug uptake study indicated a greater brain drug concentration from chitosan nanoparticles than from plain drug solution. The anti-Alzheimer potential was also evident from behavioural studies and histopathology study of rat brain. Conclusion: Thus, the chitosan nanoparticulate formulation of leuprolide acetate was found to have great potential for Alzheimer’s disease management.