Excipient Compatibility Studies Research Articles

Formulation and in-vitro anticancer activity of nilotinib immediate release and ibrutinib sustained release pellets

Background: Blood cancer is a significant contributor to mortality rates worldwide, and its prevalence is projected to rise on a global scale. This trend places considerable strain on healthcare systems and necessitates the expedited development of innovative treatments by pharmaceutical firms to remain competitive. Conventional pellets produce rapid plasma drug levels, but they might cause side effects, decrease effectiveness, and lead to poor therapeutic management. Ibrutinib and Nilotinib are employed to treat leukemia patients. Methodology: The current research aims to formulate, characterize, and anticancer effect of Nilotinib immediate release (NIR) and Ibrutinib sustained release (ISR) seal sugar-coated pellets. Micrometric properties estimated the characterization of the drug pellets, and surface morphology was estimated using scanning electron microscopy. Drug excipient compatibility studies, stability studies, and in-vitro drug release were accessed. Result & Discussion: The results of pellet formulations FNI-1 to FNI-5 showed that FNI-5 formulations showed 100±6.0 µm size and possessed excellent mechanical strength for giving pellets a good self-life; also, due to the higher drug content up to 99%, FNI-5 was the best suited for pellet formulation and because NIR showed 99.18 ± 2.12 drug release at 2h and ISR 99.03±3.74% up to 12h so that anticancer concentration maintained for prolonged period. The standard dose for cytotoxicity against the THP-1 cell line of Nilotinib was found to be 200 mg, and the maintenance oral dose of Ibrutinib was 140mg, with four times the intake of the drug up to 560 mg. In an in vitro study in FNI-5 (final formulation), the dose of Ibrutinib was reduced to 420 mg. Conclusion: A synergistic effect of Ibrutinib and nilotinib drugs was observed in the inhibition of cancer cell growth, with an IC50 value of 4.585 µg/mL

Mixture Experimentation in Pharmaceutical Formulations: A Tutorial.

Mixture experimentation is commonly seen in pharmaceutical formulation studies, where the relative proportions of the individual components are modeled for effects on product attributes. The requirement that the sum of the component proportions equals 1 has given rise to the class of designs, known as mixture designs. The first mixture designs were published by Quenouille in 1953 but it took nearly 40 years for the earliest mixture design applications to be published in the pharmaceutical sciences literature by Kettaneh-Wold in 1991 and Waaler in 1992. Since then, the advent of efficient computer algorithms to generate designs has made this class of designs easily accessible to pharmaceutical statisticians, although the use of these designs appears to be an underutilized experimental strategy even today. One goal of this tutorial is to draw the attention of experimental statisticians to this class of designs and their advantages in pursuing formulation studies such as excipient compatibility studies. We present sufficient materials to introduce the novice practitioner to this class of design, associated models, and analysis strategies. An example of a mixture-process variable design is given as a case study.

Reactivity of N terminal histidine of peptides towards excipients/impurity of excipients: A case study of liraglutide excipient compatibility study

The selection of quality excipients is a crucial step in peptide formulation development. Apart from excipient incompatibility, process-related impurities or degradants of an excipient can interact with peptide-active pharmaceutical ingredients, forming the interaction products. The formaldehyde has been reported as an impurity of excipient in polyethylene glycol, glycerol, magnesium stearate, microcrystalline cellulose, mannitol, etc. The peptide contains various amino acids such as histidine, lysine, and arginine having free amine groups. These amine groups act as strong nucleophile and can increase the reactivity of peptides. PLGA is the most widely used biodegradable polymer in sustained-release formulations. The hydrolysis of PLGA generates glycolic acid and lactic acid impurities, which can form the interaction product with the amines of peptides. During the formulation development of Liraglutide, we have found few interaction products. The systematic characterization and mechanistic understanding of these interaction products lead us to imidazopyrimidine, glycolyl, and lactolyl moieties. These interaction products have been characterized thoroughly with the use of LC-HRMS, MS/MS, and hydrogen-deuterium exchange mass studies. The study revealed that the reactivity of N-terminal histidine must be considered for formulation development. Moreover, the quality of excipients with respect to presence of impurities must be considered as critical material attributes.

Impact of Penetration Enhancer and Natural Oil on Transdermal Delivery of Modified Karaya Gum Gel

The etodolac based modified karaya gum (MKG) gel was developed using 32 factorial design to enhance the therapeutic effect of gel to treat inflammation. Gels were prepared with different concentrations of MKG and arachis oil using 32 factorial design. The percentage of drug content was found in the range of 96 to 99%, viscosity results shown in the range of 842 CPS to 2560 CPS and in vitro drug release was found to be in range of 38% to 98% respectively. Whereas ex-vivo permeation studies of etodolac gel and pure etodolac solution across the burned pig skin were shown 72% and 42% respectively. The drug and excipient compatibility studies by FTIR confirms that, there is no major functional group change was observed. The results concluded that, the combination of MKG and arachis oil were improved the penetration of etodolac through burned pig skin thereby the combination of PE and oil successfully enhanced the therapeutic effect of etodolac.

Reverse‐phase high‐performance liquid chromatography methodology for film‐forming mafenide spray: Compatibility, assay, and in‐vitro release evaluation using Franz vertical diffusion cell apparatus

AbstractThis paper described a short and precise reverse‐phase high‐performance liquid chromatography (HPLC) method for quantifying mafenide in a film‐forming spray and preliminary in‐vitro release study. Following the International Council for Harmonization guidelines Q2 (R1), the method was validated. The chromatographic separation was achieved using a 10 mM potassium dihydrogen phosphate solution (mobile phase A) mixed with HPLC‐grade methanol (mobile phase B) in an 85:15 v/v ratio. Inert Sustain C8 (4.6 × 250 mm), 5 μm column was selected as the stationary phase. The flow rate was set as 0.8 mL/min, and detection was carried out at a wavelength of 222 nm. The developed HPLC method showed an accuracy between 98% and 102%. The primary diffusion study of film‐forming spray was performed using the Franz vertical diffusion cell apparatus. It was observed that an average of 26.94% of drug releases at 24 h. This indicates the drug has a slower release rate and shows local pharmacological action. The Weibull dissolution model was more fitting with regression square 0.9953. Furthermore, the drug excipient compatibility study revealed no interactions as the only drug peak was found in the chromatographic method, indicating that the chosen excipients were appropriate for a stable formulation.

FORMULATION AND EVALUATION OF NIOSOMAL GEL OF AZELAIC ACID FOR ANTIACNE ACTIVITY

Objective: This study aimed to develop niosomes loaded with azelaic acid (AA) to administer in gel form. The primary objective was to achieve controlled and sustained release of the drug while minimizing potential side effects. Methods: Niosomes were fabricated using a combination of various non-ionic surfactants and cholesterol through the application of thin film hydration technique. Furthermore, the processing parameters were optimized and drug excipient compatibility study was conducted using FTIR spectroscopy. The formulations were extensively characterized in terms of entrapment efficiency, particle size, shape, and in vitro release. Subsequently, the improved niosomal dispersions were employed to formulate gels, which underwent analysis to evaluate their visual properties, pH, and rheological behavior. Stability study was also conducted. Results: Total 15 formulations were prepared, out of which 3 formulations F3, F9 and F15 were found to exhibit maximum entrapment efficiency. These formulation were having particle size 260.1 nm, 272.3 nm and 226.3 nm respectively. In vitro drug release was found to be maximum in F9 formulation. The release was found to be dose-dependent across all formulations, with regression values between 0.97 and 0.99, confirming first-order release kinetics. FTIR spectra indicated the absence of any drug-cholesterol-nonionic surfactant interaction in the formulation. The niosomal gel formulations exhibited optimal performance when stored within the temperature range of 4 to 8 °C. Conclusion: This investigation demonstrates the utility of the thin film hydration technique in effectively incorporating poorly water-soluble medications such as azelaic Acid (AA) into niosomes, resulting in high entrapment efficiency. These findings suggest that niosomes containing AA, when topically applied as a gel, have the potential to be an efficacious treatment for acne.

A QBD WITH THE FRACTIONAL FACTORIAL DESIGN WAS USED TO MATCH THE SIMILARITY BETWEEN RANOLAZINE EXTENDED-RELEASE TABLETS 500 MG AND 1000 MG

Objective: Formulation and development of Ranolazine extended-release Tablets 500 mg and 1000 mg by using QBD with Fractional factorial design to match the similarity with Branded formulation (RANEXA®). Methods: Ranolazine extended-release tablets were developed by using various polymers, Polyquid PA100 and ETHOCEL TMstandard 7 premium and Hypromellose with a wet granulation process. QBD (Quality by Design) approach was used to identify the formulation and process variables that may affect the CQAs (critical quality attributes). Excipient compatibility studies were conducted to identify the interaction between API (active pharmaceutical ingredient) and selected excipients. Additionally, using a two-level, fractional factorial (22+3) design, the DOE (design of experiments) was employed to confirm the impacts of key process factors (fluid uptake and kneading time) on the formulation's ability to match the dissolution (f2) compared to RLD (reference listed drug) and establish a stable formulation. Results: Initial risk assessment was carried out to identify the various attributes such as API flow properties, solubility, PSD, Hygroscopicity, formulation, and process variables to impact the quality of the drug product. Flow properties of API indicate poor flow. Drug and excipients compatible study results indicate that excipients used in the compatibility study are considered compatible with the active ingredient. As per the saturation solubility studies and sink conditions, dissolution media was selected. Significant differences were found among the drug release profile by examining the various levels of polymers and binders. Using a two-level, fractional factorial (22+3) design, optimum process parameters were identified with selected formulation to match the dissolution (f2) similarity with the reference listed drug (RLD); finally, XRD (X-ray diffraction) studies confirm that the crystalline polymorphic forms (Form 1) peaks in optimum formulation (F07) comparable to the reference listed drug. Conclusion: Optimized formulation and process were established with QbD (quality by design) that provides the consistent drug release to match the f2 similarities with the extended-release tablets of RANEXA®(Ranolazine) 500 mg and 1000 mg.

VITAMIN C AND CRANBERRY EXTRACT EFFERVESCENT TABLET FORMULATION, CHARACTERIZATION, AND EVALUATION

Background: Effervescent floating tablets are used oral dosage form, to enhance the patient compliance, drug bioavailability and to increase the absorption rate. Cranberry (Vaccinium macrocarpon), widely used as a preventive agent against urinary tract infections, also suggested for Type II diabetes, myalgic encephalomyelitis, scurvy, and as a diuretic pill for being rich in nutrients and anti-oxidant properties. Objectives: The aim of the study is to formulate and evaluate the effervescent tablets of Cranberry and Vitamin C. Methodology: As per defined criteria of US FDA, effervescent tablet as per composition is formulated by citric acid and sodium bicarbonate and intended to dissolve in water before administration. Active substance and excipient compatibility studies were done by UV and FTIR, resulted absence of any interaction. Pre-formulation studies including Bulk density, tapped density, angle of repose, Hausner’s ratio, Carr’s index and water content. Results: Formulations were evaluated for weight variation, thickness, hardness, pH of solution, drug dissolution time, content uniformity as defined specification of U.S.P and BP. Stability and storage condition studies were also monitored with average results of 96% drug assay and dissolution. All the results showed excellent formulation of tablet and flow properties of granules. Conclusion: Further studies required to approach targeted and spontaneous release of active as optimized effervescence maybe helpful in delivery of actives and enhancing patient compliance.

Application of D-Optimal Mixture Design in the Development of Nanocarrier-Based Darifenacin Hydrobromide Gel.

Darifenacin hydrobromide, a BCS Class II drug, is poorly bioavailable due to extensive first-pass metabolism. The present study is an attempt to investigate an alternative route of drug delivery by developing a nanometric microemulsion-based transdermal gel for the management of an overactive bladder. Oil, surfactant, and cosurfactant were selected based on the solubility of the drug, and surfactant: cosurfactant in surfactant mixture (Smix) was selected at a 1:1 ratio as inferred from the pseudo ternary phase diagram. The D-optimal mixture design was used to optimize the o/w microemulsion wherein the globule size and zeta potential were selected as dependable variables. The prepared microemulsions were also characterized for various physico-chemical properties like transmittance, conductivity, and TEM. The optimized microemulsion was gelled using Carbopol 934 P and assessed for drug release in vitro and ex vivo, viscosity, spreadability, pH, etc. Drug excipient compatibility studies showed that the drug was compatible with formulation components. The optimized microemulsion showed a globule size of less than 50 nm and a high zeta potential of -20.56 mV. The ME gel could sustain the drug release for 8 hours as reflected in in vitro and ex vivo skin permeation and retention studies. The accelerated stability study showed no significant change in applied storage conditions. An effective, stable, non-invasive microemulsion gel containing darifenacin hydrobromide was developed. The achieved merits could translate into increased bioavailability and dose reduction. Further confirmatory in vivo studies on this novel formulation, which is a cost-effective & industrially scalable option, can improve the pharmacoeconomics of overactive bladder management.

Formulation development and evaluation of orodispersible tablet of Azelnidipine by factorial design and its comparison with the marketed formulation

The aim of the present investigation was to prepare an orodispersible tablet of Azelnidipine using superdisintegrant agents like croscarmellose sodium by direct compression method. These formulated tablets were evaluated for drug content, weight variation, friability, hardness, solubility study also, and drug excipient compatibility study. Based on data obtained from pre-compression and post-compression evaluation of batches as well as the factorial design model study f7 batch was selected as the optimized batch. Based on the result obtained from the dissolution profile study it was concluded that the formula responsible for Azelnidipine tablets gives the fastest disintegration as well as absorption of the drug as compared to the conventional marketed tablet dosage form.

Formulation And Evaluation Of Berberine Hydrochloride Film Coated Tablet

The purpose of the present study was to formulate and evaluate Berberine HCl Film coated tablet. Preformulation studies of API were done. The film coated tablets have advantages over conventional oral dosage forms, film coated tablet also influences the release of drug after compression. Film coating also help in making the tablet with good taste masking properties and excellent mechanical strength. It was revealed in the study that cellulosic coating materials were unable to resist the compression forces whereas hydroxypropyl methyl cellulose co-polymers resist the forces. Furthermore, aqueous dispersions of hydroxypropyl methyl cellulose co-polymers showed high flexibility as that of cellulosic materials thereby providing resistance from destructive compressional forces. The Preformulation characteristics were done as per the Pharmacopeial specifications. The drugs and excipients compatibility studies were carried out by FT-IR spectroscopy. Various pre-compressional parameters like bulk density, tapped density, compressibility index and Hausner’s ratio and post-compressional parameters like weight variation, thickness, hardness, friability, disintegration time and drug release were studied. The spectra elucidate that there was no interaction between Drug and excipients. In order to achieve the best optimized product, five different formulations were developed using diluents, binder, glidant, lubricant, and different concentrations of super-disintegrant. The tablets were prepared by using wet granulation method. Optimization was done and it was found that release profile was found to be best with super-disintegrant that is Crospovidone and Enhance DT. Protectab HP-1 coating was done on Berberine HCl tablets. In-vitro release was carried out in medium 6.8 pH Phosphate buffer. The formulation F-5 was showed better drug release and selected as an optimized formulation.

Modafinil-excipient compatibility study using differential scanning calorimetry.

Drug excipient compatibility studies are considered important in successful formulation of drug products. Suggested methods for this purpose are thermal techniques under isothermal or nonisothermal conditions. In this study, modafinil, a wakefulness-promoting drug, was investigated under nonisothermal conditions using differential scanning calorimetry. Four different heating rates, 5, 10, 15, and 20°C/min, were performed for modafinil pure material and its physical mixtures with magnesium stearate (MgSt) or Gelucire 48/16. Activation energy (Ea) was calculated from the straight line of plotting a function of heating rate versus temperature and found that modafinil-Gelucire physical mixture increased Ea. This indicates drug-excipient interaction, supported by evidence from Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. No significant interaction was detected with MgSt.

Development, Optimization and Evaluation of Herbal Patch Formulation for Acne Treatment

Background: More than 85% of young people around the world suffer from acne vulgaris, which is the most prevalent chronic inflammatory skin illness. The study’s objective was to develop a herbal patch formulation contained quercetin, curcuminoids, and berberine HCl for the treatment of acne that utilizing ethyl cellulose and HPMC K4M as polymers and propylene glycol as a plasticizer. Materials and Methods: Drug excipient compatibility study was performed using FT-IR. Preliminary trial was done for screening of polymers and plasticizer concentrations. The combined influence of the two independent variables, namely the concentration of HPMC K4M and ethyl cellulose, on the dependent variables, tensile strength and cumulative % drug release at 24 hr, was examined using a 32 full factorial design. Patches were evaluated for physicochemical parameters. Results: Drug excipient compatibility study revealed that drug and excipients are compatible with each other. The optimized formulation (C0) showed tensile strength 2.56 kg/cm2, cumulative percentage drug release of quercetin, berberine HCl, and curcuminoids at 24 hr were 94.02%, 64.66%, and 94.21%, respectively. Tensile strength increased with an amount of HPMC K4M and Ethyl cellulose increases, the cumulative percentage of drug release decreased as HPMC K4M and ethyl cellulose concentrations were raised. Conclusion: Optimized herbal patch formulation had shown good physico-chemical and mechanical properties. The research shows that the developed formulation has the potential to be a useful replacement for the present medications in the market.

STEP TOWORDS THE FORMULATION OF INJECTABLE HYDROGEL: PREFORMULATION STUDIES OF TERIFLUNOMIDE

Purpose: The aim of formulation of this hydrogel is to treat the osteoarthritis which is one of the common inflammatory autoimmune disorders of joints. The use of conventional drugs like NSAIDs having various side effects.
 The aim of our research was to develop a formulation of injectable hydrogel containing teriflunomide. This study will be helps us for the development of stable, robust and therapeutically effective dosage form.
 Method: Solubility of Teriflunomaide was determined by using various solvents. By using infrared spectrum and absorption maxima the purity of sample was checked. With the help of UV spectrophotometer standard UV curve was developed. Drug excipients compatibility studies were performed using Fourier transform infrared spectroscopy, differential scanning colorimetry, partition coefficient and also short term drug solution stability studies were performed.
 Result: Teriflunomide is soluble in methanol & 0.1 N NaOH on the other hand poorly soluble in distilled water, phosphate buffer (pH 7.4) and 0.1 N HCl. Absorption maxima was observed at 292nm and infrared spectrum was showing the characteristic peaks. The standard curve obtained was linear with correlation coefficient below 1. Log P value obtained at 2.78 it confirms that teriflunomide is having both hydrophilic & hydrophobic nature. After the entire short term stability studies drug was found to be stable in short term stability studies.
 Conclusion: The studies like melting point, FTIR etc suggested that drug selected for the formulation was found to be pure. Partition coefficient values suggested that it is having both hydrophilic and hydrophobic nature. Results obtained from short term stability studies were suggested that drug is stable showing no degradation on phosphate buffer which confirmed by no shift of λ max.

Formulation and Evaluation of Posaconazole Bilayer Delayed Release Tablets Using Solid Dispersion Technique

The aim of present investigation to formulate bilayer tablets of posaconazole by using solvent evaporation technique. Posaconazole belongs to BCS class 2 which has high permeability and low solubility. In order to enhance the solubility of posaconazole solvent evaporation technique was applied where HPMC AS was used as carrier. This tablet consist of two layers of which first layer serves as loading dose which produce immediate release of drug and second layer serves as maintenance dose that provide controlled release of drug. The whole bilayer tablet is coated with Eudragit L30D55 to produce delayed release and protect drug from acid environment in stomach. The drug excipient compatibility study was performed by FTIR and no interaction was found. Croscaramellose was used in immediate release layer as superdisintegrant. Methocel K100M and Methocel E5M are used for sustain drug release in control release layer. The powder blend for evaluated for flow properties like angle of repose, bulk density, tapped density, Carr’s index and Hausner’s ratio which showed good results. Invitro dissolution studies was performed with USP dissolution apparatus 2- Paddle type. Invitro dissolution was performed for 2 hours in 0.1N HCl which showed no drug release followed by 6.8 phosphate buffer for 12 hours. The bilayer tablet showed initial release to provide loading dose of drug followed by controlled release up to 12 hours. Change in concentration of polymer and superdisintegrant showed impact on drug release profile. Increase in concentration of superdisintegrant in immediate release layer showed increased % drug release. Whereas increase in sustain release polymers in controlled release layer showed decrease % drug release. F9 batch showed satisfactory release up to 100% for 12 hours and was selected as best formulation. Reproducible batch for F9 was formulated and called F10 which also showed satisfactory results.

Development and Characterization of Griseofulvin Nanosponges to Enhance Bioavailability

The pharmaceutical industries are more interested in development of novel drug delivery system to overcome the disadvantages of traditional drug delivery system. Now a days, fungal infections are increasing worldwide. Hence the demand of novel dosage form is increased with improved therapeutic effect and minimum side effect. The main aim of this study was to develop griseofulvin loaded ß -cyclodextrin based nanosponges for improving dissolution, oral bioavailability. In the present study, the griseofulvin loaded Nano sponges were prepared by emulsion solvent diffusion method. The six different formulation batches were formulated with varying concentration ratio of drug and polymer. The Preformulation study of the drug was done by UVvisible spectrophotometer. Drug, polymer and excipient compatibility studies were analyzed by FTIR studies. The prepared Nanosponges formulation was evaluated for particle size, zeta potential, polydispersity index, scanning electron microscopy and in-vitro drug release studies. The SEM studies showed the highly porous structure of griseofulvin loaded nanosponges having a sponges-like shape. The entrapment efficiency of optimized batch F4 was found to be 97.69±0.006%. The particle size and zeta potential of optimized batch F4 was found to be 488.59nm and -20.77 respectively. The in-vitro drug release of optimized batch F4 showed the maximum drug release of 75.56% in 8 hrs. The current study successfully developed griseofulvin loaded ß - cyclodextrin based nanosponges to improve dissolution rate, oral bioavailability and masking bitter taste. The polymer used in preparation of nanosponges shows efficient drug release. Griseofulvin loaded nanosponges drug delivery showed prolonged release which is beneficial for chronic fungal infection. Another advantage of formulating novel dosage forms is reduction in dose, dosing frequency and reduced side effects.

Design and Optimization of Floating Microspheres Using Abelmoschus esculentus Natural Polymer

The main objective of the present research study was to fabricate Vildagliptin floating microspheres by ionotropic gelation using natural polymer, Abelmoschus esculentus obtained from the fruits of Abelmoschus esculentus in combination with sodium alginate. Microspheres were prepared and optimized using central composite rotatable design model using design expert software version 12 .The study is focussed on the interaction effects of the three independent variables, natural polymer concentration, sodium alginate concentration and crosslinker concentration, optimization of formulations response surface methodology was used . drug –excipient compatibility studies were carried out by infrared spectroscopic studies. Infrared spectroscopic studies clearly shown that drug and excipients were compatible. Totally 15 formulations were generated taking 8 factorial points, 6 axial points and 1 centre point. Response surface methodology was used to optimize the formulations. To investigate the responses %cumulative drug release, floating time and floating lag time Response surface methodology was used Polynomial equations and model plots of 3 dimensional model surface plots were generated. Vildagliptin optimized microspheres were formulated and a second order, model quadratic model was used to study influence of formulation factors on response variables. Experimental data of Statistical analysis exhibited good coefficient of regression for cumulative in vitro drug release Regression F –ratios for the experimental variables were significant. The experimental values and predicted values are agreed. All fifteen formulations exhibited % yield of 94.35-99.99%, particle size of 124-441µm, %swelling index 64.52-89.65%, floating time of 10.16 to 13.16 and floating lag time of 30.31 to 46.98 sec. F4 formulation is optimized based on cumulative % in-vitro drug release at 2nd hour, 12th hour, floating lag time and floating time values. Predicted and observed results are in agreement 95% confidence intervals. Based on investigation, RSM is the good tool for optimization of formulations.

Fabrication and Characterization of Lercanidipine Hydrochloride Solid Dispersions by Fusion Technique

The authors aimed to design solid dispersions with Lercanidipine Hydrochloride (LCD) with PVP K-30, Poloxamer-188, and HPMC K4M as carriers. Various mixtures of LCD and Polymers (PVP K-30, Poloxamer-188, and HPMC K4M) were made in 1:1, 1:3, 1:5 and 1:7 ratios, and the solid dispersion was prepared by melting tactic, later compressed into tablets. Drug excipient compatibility studies were examined by DSC and FTIR studies. LCD was found to compatible with carriers used. The LCD solid dispersion was measured for physicochemical quality both in solid dispersions SD, and tablet states. The LCD solid dispersions found to have excellent flow possessions and compression assets. The yield of prepared solid dispersion was observed to be more than 90%), and the formulation LPOX-3 has showed a good yield of 98.9±1.95%, The tablets which were compressed from solid dispersions were found to have a uniform in size, shape, color, and consistency. The tablets were observed to have a uniform in thickness, and weight and ranged from 300.2±1.64 to 301.7±1.64 mg. The loss on friability was less than 1%, and the hardness was more than 4 Kg/cm2 indicates significant mechanical strength and the LCD content was also found to be uniform (96.8±1.35 to 99.9±2.34). The solubility of LCD was found to be good in 0.1N HCl and diminished with an increase in pH of the buffer. LCD released from the tablets were firstly by eruption followed by zero order. The dissolution was found to be good in solid dispersions with LCD: Poloxamer-188 at the ratio of 1:5. The results obtained were satisfactory. The study concludes that LCD solid dispersions (LPOX-3) with 1:5 ratios of LCD and Poloxamer-188 was found to be a better carrier than PVP K-30, and HPMC K4M in increasing the solubility of LCD from the solid dispersions.

Formulation Development of Tranexamic Acid loaded Transethosomal Patch for Melasma

Nanotechnology based drug delivery systems are employed to overcome the hitches associated with conventional therapies. Melasma is a chronic, acquired, therapeutically challenging, universally relapsing hyperpigmentation disorder that causes greyish-brown spots on the skin, mainly on the face. Tranexamic acid (TXA) is a newer medication used to treat melasma that can be administered topically as well as orally. TXA has an oral bioavailability of 30-50%. The current study aimed to create a transethosomal (TEL) patch, for transdermal delivery of TXA for the treatment of melasma as an alternative to the oral route's hindrance. The cold technique was used to prepare TEL. They are composed of phospholipid (Phospholipon 90G), ethanol, water, and an edge activator (sodium cholate). Drug excipient compatibility study was done using Differential scanning colorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy techniques. TEL batches were further characterized based on particle size (PS) and entrapment efficiency (EE). The optimized batch's PS and EE were found to be 72 nm and 94%, respectively. The average zeta potential was -16 mV, indicating a stable formulation. Vesicular morphology was monitored by Scanning electron microscopy (SEM) analysis. The in vitro and ex vivo release of TXA was evaluated by Franz diffusion study and showed the release of about 93.97% over the period of 24 hrs, which was better than that of a conventional topical cream. All of the above findings showed that TEL may be a good carrier alternative for delivery of TXA into deeper layers, and hence good for treating melasma.

FORMULATION AND IN-VITRO CHARACTERIZATION OF ABACAVIR SULPHATE EFFERVESCENT FLOATING TABLETS

fter oral administration of Abacavir, rapid absorption occurs from upper part of gastro intestinal tract with peak concentrations occurring at 0.63 - 1 hr after dosing. Conventional drug therapy with tablets produce relatively rapid and high peak blood levels that requires frequent administration to maintain effective range of plasma drug levels. This conventional therapy leads to reduced effectiveness with poor therapeutic management. To overcome the inadequacy of conventional therapy with tablets, floating sustained release Abacavir tablets were developed. Floating sustained release Abacavir Sulphate tablets were prepared by using direct compression method. Tablet were formulated using Ethyl Cellulose with hydrocolloids like Hydroxypropyl Methylcellulose (HPMC K4M) and Carbopol 974P as release retarding polymers, Sodium bicarbonate (NaHCO3) and Citric acid as effervescent agents. Tablets were then evaluated for various physical parameters including hardness, thickness, weight variation, friability, drug content, in-vitro buoyancy, Swelling index and Invitro gastro retentive drug release were conducted. Drug and excipient compatibility studies show that they are compatible with each other. The optimized formulation (F9) shows the hardness of 5.7kg/cm2, tablet thickness of 2.74mm, 0.45% of friability, in-vitro buoyancy was up to 6 hours and % drug release was 90.56% in 6 hours. Drug release kinetics was found to follow non-fickian diffusion. Hence, F9 is considered as optimized formulation based on invitro buoyancy and % drug release.