ENHANCEMENT OF SOLUBILITY AND BIOAVAILABILITY OF BCS CLASS-II AMBRISENTAN: IN VITRO, IN VIVO AND EX VIVO ANALYSIS

Objective: The aim of this investigation was to enhance the solubility and bioavailability of the BCS class II poorly water-soluble drug ambrisentan by solid dispersion (SD) techniques using Gelucire 50/13 as a hydrophilic carrier. Methods: Solid dispersion of ambrisentan was prepared by kneading method using different dug: carrier ratios. Prepared SD was characterized for solubility, drug content, percentage yield, in vitro dissolution, ex vivo permeation and bioavailability. Solid-state characterization was performed by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Results: All the SDs formulations showed increase in drug solubility and dissolution when compared with its pure form. Aqueous solubility of the drug was found to be increased 8.23 fold in SD. DSC study showed that endothermic peak of the drug was disappeared in spectra of SD, confirming its amorphous conversion, XRD study revealed the reduction to almost absence of specific high-intensity peaks of drug which confirmed the reduction of crysatallinity of ambrisentan in SD. SEM of optimized SD formulation demonstrates the complete encapsulation and solubilization drug. In vitro dissolution study showed that optimized SD formulation (ASD4) gives the faster drug release of 101.5% in 60 min, as compare to its pure form and other SD formulations. Conclusion: Solid dispersion ASD4 prepared with 1:4 drug to carrier ratio showed the highest drug solubility and in vitro dissolution. The ex vivo and in vivo studies performed on optimized formulation ASD4 showed enhancement in drug permeability and bioavailability in Gelucire 50/13 based SD formulation.

DEVELOPMENT, OPTIMIZATION AND EVALUATION OF PULSATILE DRUG DELIVERY CAPSULES LOADED WITH CARVEDILOL BY APPLYING QUALITY BY DESIGN

Objective: The purpose of this research is to find the best way for designing carvedilol pulsatile drug delivery system capsules. Methods: The research paves the way to improve the method of preparing carvedilol pulsatile drug delivery by adjusting critical material attributes (CMA) such as coating polymer concentration, critical process parameters (CPP) such as inlet temperature and atomizing air pressure, and their impact on critical quality attributes (CQA) like particle size (PS in nm), entrapment efficiency in percentage (% EE) and amount of drug delivered in percent (%ADR) at 12 h in the carvedilol pulsatile pellets filled capsules by applying the Box-Behnken design. By varying the polymer concentration and process parameters, nearly 15 formulations were created. Results: Based on the influence of CMA, CPP on CQA, the formulation CP13 was determined to be the most optimized formulation among the 15 formulations. The optimized levels of CMA were found to be-1 level of coating polymer concentration and CPP was found to be-1 level of inlet temperature, 0 level of atomizing air pressure and it optimized CQA like PS was found to be 1017.5±8.4 nm, % EE was found to be 96.8±2.8 %, % ADR at 12 h was found to be 88.4±3.4 %. Carvedilol Pulsatile drug delivery system was designed by using optimized fluidized bed coater in order to decrease the usage of attributes, decrease the productivity cost and enhance the usage of specific attributes at fixed concentration for further manufacturing scale. Conclusion: By the current results it was concluded that the optimized CMA and CPP that shown in the results are the suitable attributes for the best formulation of carvedilol pulsatile drug delivery system capsules.

PHYSICAL CHARACTERIZATION OF IN SITU OPHTHALMIC GEL: A CONCISE REVIEW

In situ ophthalmic gel is a type of eye drug preparation that has a higher bioavailability value and has a longer contact time with maximum therapeutic effect and with minimal side effects compared to conventional eye preparations. The preparation of ophthalmic in situ gel is required characterization to make sure that the prepared preparations meet the standards and are safe when used. This journal review aims to look at the methods used in characterizing physical properties in in situ ophthalmic gel formulations with different active substances such as rheology studies, organoleptic tests, pH, clarity, and gelling capacity. In order to get the best formulation of in situ ophthalmic gel preparations so as to provide maximum therapeutic effect.

DEVELOPMENT AND CHARACTERIZATION OF ORO-DISPERSIBLE TABLETS OF METFORMIN HYDROCHLORIDE USING CAJANUS CAJAN STARCH AS A NATURAL SUPERDISINTEGRANT

Objective: The aim of the research work was to explore the use of Cajanus cajan (Pigeon pea) polysaccharide as a superdisintegrant. The novel superdisintegrant has been evaluated for its action by incorporating it into orodispersible tablets of Metformin Hydrochloride. Methods: Cajanus cajan starch was extracted from its seeds and superdisintegrant was developed by microwave modification of the extract. Various characterization tests such as gelatinization temperature, water absorption index, pH, and viscosity were used to identify the microwave-modified polysaccharide. The orodispersible tablets were made using a direct compression process employing varying concentrations of modified Cajanus cajan starch. Prepared tablets were tested for several pre and post-compression parameters and compared with a well-established synthetic superdisintegrant, sodium starch glycolate. The stability studies were conducted on an optimized formulation. Results: Fourier transform infrared spectroscopy study showed that the drug had no interactions with the microwave-modified Cajanus cajan starch. SEM confirmed that Cajanus cajan starch granules exhibited intact granular structure in oval shapes and smooth surfaces. After microwave modification, the Cajanus cajan starch component lost its granular structure, which further led to the generation of surface pores and internal channels, causing overall swelling responsible for superdisintegrant activity. The optimized formulation (ODF5) containing 15 % modified Cajanus cajan starch performed better in terms of wetting time (22.21 s), disintegration time (53.3 s), and in vitro drug release (92%), as compared to formulation prepared by synthetic superdisintegrant (ODF1). Conclusion: The present investigation concluded that modified Cajanus cajan starch has good potential as a superdisintegrant for formulating oro-dispersible tablets. Furthermore, modified Cajanus cajan starch is inexpensive, non-toxic and compatible in comparison with available synthetic superdisintegrants.

LC-MS/MS CHARACTERIZATION OF FORCED DEGRADATION PRODUCTS OF TUCATINIB, A NOVEL TYROSINE KINASE INHIBITOR: DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD

Objective: The current study focused on the development, validation, and characterization of forced degradation products using LC-MS/MS. Methods: A simple, selective, validated and well-defined isocratic HPLC methodology for the quantitative determination of Tucatinib at a wavelength of 239 nm. An isocratic elution of samples was performed on an Inertsil ODS (250x4.6 mm, 5m) column with a mobile phase of 70:30v/v Acetonitrile and formic acid (0.1%) delivered at a flow rate of 1.0 ml/min. MS/MS was used to characterize degradation products formed in the forced degradation study. The validation and characterization of forced degradation products were performed in accordance with ICH guidelines. Results: Over the concentration range of 5-100μg/ml, a good linear response was obtained. Tucatinib's LOD and LOQ were determined to be 0.05 and 0.5, respectively. According to standard guidelines, the method was quantitatively evaluated in terms of system suitability, linearity, precision, accuracy, and robustness, and the results were found to be within acceptable limits. The drug was degraded under acidic, alkaline, and reduction conditions in forced degradation studies. Conclusion: The method was found to be applicable for routine tucatinib analysis. Because no LC-MS/MS method for estimating tucatinib and its degradation products has been reported in the literature. There is a need to develop a method for studying the entire tucatinib degradation pathway.

SIMULTANEOUS ESTIMATION OF AZILSARTAN AND CILNIDIPINE IN BULK BY RP-HPLC AND ASSESSMENT OF ITS APPLICABILITY IN MARKETED TABLET DOSAGE FORM

Objective: This study aims to build up the RP-HPLC process for Azilsartan and Cilnidipine and authenticate the RP-HPLC process according to ICH validation code Q2R1. Methods: System suitability testing was performed to discover the qualifying criterion of the method by injecting the identical standard solution of Azilsartan 40μg/ml and Cilnidipine 10μg/ml in mixture/combination in subsequent optimized chromatographic conditions and the chromatogram was recorded. Moreover, the planned method was validated as per ICH guideline Q2R1 for the following parameters: linearity and range, precision, accuracy, robustness, and determined % recovery. Results: The outcomes of %RSD for retention time and peak area were found to be 0.65 and 1.32 for Azilsartan and 0.85 and 1.90 for Cilnidipine. The correlation coefficient, y-intercept, slope of the regression line were 0.9996,-1127.1, 3313.9, and 0.9993, 1460.2, 2876.4 for Azilsartan and Cilnidipine, respectively. Moreover, the range of this method was observed to be 40-240μg/ml and 10-60 μg/ml for Azilsartan and Cilnidipine, standard concentrations respectively. The % RSD achieved for precision (repeatability) was observed in the range of 1.57 to 2.43 for Azilsartan and 0.70 to 1.88 for Cilnidipine. The % accuracy was found in the range of 96.96 to 101.92% w/w for Azilsartan and 99.19 to101.96%w/w for Cilnidipine. The percent recovery values achieved for Azilsartan were in the range of 99.87 to 106.39% w/w and for Cilnidipine in the range of 94.51 to 105.96% w/w. Conclusion: The author concludes that the simultaneous estimation of Azilsartan and Cilnidipine with predefined objectives was successfully achieved. Moreover, the method was found to be steadfast for the quantification of Azilsartan and Cilnidipine in marketed tablet dosage forms.

EVALUATION OF ANTI-GLYCATION EFFECT AND SAFETY OF SERUM ANTI-AGING FORMULATION CONTAINING GOLD NANOPARTICLES (AUNP) USING SIDAGURI EXTRACT (SIDA RHOMBIFOLIA)

Objective: The purpose of this study is to determine the anti-aging properties and safety of serum containing gold nanoparticles (AuNP) using Sidaguri extract (Sida rhombifolia) through their anti-glycation effect. Methods: The anti-aging effect of serum was performed in vitro by measuring advance glycation end products (AGEs) formed during incubation using a Microplate reader, and safety of serum was performed using hen’s egg chorioallantoic membrane (HET-CAM) method using White Leghorn egg. Results: The study showed that serum formulation had an anti-glycation effect with inhibition percentages are 68.20±6.86% and 74.83%±19.91% for a serum containing 10% and 20% gold nanoparticles and little to no irritation potency for both serum formulations with RI value 0.0 and 0.0, respectively. Conclusion: Due to both their anti-glycation effect and irritation behavior, serum formulation containing gold nanoparticle synthesized using Sidaguri extracts could be utilized as anti-aging cosmetics in the future.

DIACEREIN-LOADED NIOSOMES (DC-NS): A NEW TECHNIQUE TO SUSTAIN THE RELEASE OF DRUG ACTION

Objective: The study's main goal is to develop a suitable niosomes (NS) encapsulated drug for anti-inflammatory effects such as diacerein (DC) and to evaluate the system's vesicle size (VS), entrapment efficiency (EE %), physical stability and in vitro release. Methods: Tween (40 and 60), cholesterol, and stearylamine were used in a 1:1:0.1 molar ratios as non-ionic surfactants. Thin film hydration was used to create the NS. Results: The higher EE% was observed with NS (F11) prepared from tween 60, cholesterol and 2.5 min sonication. These formulations' release patterns were Higuchi diffusion and first order. For the stability study, NS formulations were stored at temperature between 2-8 °C for 60 d retains the most drugs when compared to room and high temperature conditions. Conclusion: The findings of this study have conclusively shown that after NS encapsulation of DC, drug release is prolonged at a constant and controlled rate.

FORMULATION OF EFFERVESCENT GRANULES FROM RED GINGER (ZINGIBERIS OFFICINALE ROSCOE VAR. RUBRUM) EXTRACT AND ITS ANTIOXIDANT ACTIVITY

Objective: Ginger is one of the Indonesian plants that has been used as traditional medicine. The flavonoids and phenols compounds contained high antioxidant activity. This study aimed to formulate effervescent granules (EG) from red ginger (RG) extract and evaluate its antioxidant activity. Methods: The formulation of EG from RG extract was prepared by the wet granulation method using different concentrations of polyvinylpyrrolidone (PVP). Furthermore, the flowability of granules was evaluated, including flow rate, angle of repose, bulk density, tapped density, Carr's index, Hausner ratio, and effervescent time. The physical stability of granules such as organoleptic evaluation, effervescent time, and pH measurement was also evaluated after 28 d of storage, and the antioxidant activity of EG from RG extract was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Results: The result showed that the EG of RG extract was successfully prepared by wet granulation with a concentration of 15%. In addition, the flowability study showed that all formulas of EG from RG extract have good flow properties, and the granules showed excellent flow properties based on Carr′s index results. The effervescent time of granules remained within the acceptable range according to USP, and the physical stability did not change even after 28 d of storage. The IC50 of EG from RG extract was 283.28±3.6 ppm and has moderate in free radicals scavenging activity. Conclusion: EG from RG extract can be used as food supplements to protect the human body from free radicals and inhibit oxidases.

DESIGN, DEVELOPMENT AND EVALUATION OF MOUTH DISSOLVING TABLETS OF TOFACITINIB CITRATE

Objective: This study aims to Formulate Mouth Dissolving Tablets (MDTs) of Tofacitinib Citrate with the increase in bioavailability and patient compliance. Methods: Mouth Dissolving Tablets (MDTs) of Tofacitinib Citrate were developed by full factorial design at 32levelsand prepared by direct compression method using super integrants like sodium starch glycolate, Ludiflash. The tablets were compressed into compacts on a 10 station tablet machine. The bulk drug was characterised by determining, MP, Solubility, pH and FTIR spectra. Results: The weight variation, hardness and diameter, thickness, friability, drug content, wetting time, in vitro disintegration time and in vitro dissolution studies, and stability study, tablet thickness, weight variation and drug content post compression parameters remained consistent and reproducible. All the formulations showed, almost 100 percent of drug release within 75 min. Formulations F1, F2 and F3 were prepared with 5 mg of SSG and 20 mg, 30 mg, and 40 mg Ludiflash which shows % release of drug in the order of F1<F2<F3. Formulations F4, F5 and F6 were prepared with 10 mg of SSG and 20 mg, 30 mg, and 40 mg Ludiflash which shows % release of drug in the order of F4<F5<F6. Formulations F7, F8 and F9 were prepared with 15 mg of SSG and 20 mg, 30 mg, and 40 mg Ludiflash which shows % release of drug in the order of F7<F8<F9. Conclusion: It is concluded that the amount of superdisintegrants decreases disintegration time of tablets, decreases wetting time, increases the cumulative % drug release causes better absorption.