Invitro Dissolution Research Articles

Content Uniformity and Invitro Dissolution of Amlodipine Half Tablets

Tablet splitting technique is a practice that is carried out in hospitals and community pharmacies. The aim is to achieve dose flexibility, reduce tablet size, ease swallowing, and save cost. This technique is prone to variation in the weight of split tablets, mass loss, and content uniformity. Its effectiveness is subject to the tablet characteristics, method of splitting, and patient’s knowledge and skill. This practice increases the risk of inaccurate dosing, uneven distribution of drug substances, and potential loss of efficacy or adverse effects. This study aimed to determine the effect of splitting amlodipine tablets on weight variation, content uniformity, and in-vitro dissolution. Four brands of amlodipine 10mg tablets from the Kenya pharmaceutical market were evaluated. For each brand, weight variation and content uniformity tests were conducted as per the European Pharmacopoeia. Dissolution test was performed on 6 split tablets according to the British Pharmacopoeia. All the brands of amlodipine half tablets tested for weight variation were within acceptable limits. Only one individual mass was outside the 85-115% limit of the average weight, being 83.87%. Three of the four brands complied with the content uniformity test. One brand had 2 split tablets having amlodipine content out of the limit of 85-115%. Three brands complied with the dissolution test requirement for amlodipine tablets at the S1 stage. One brand had at least 75% of the amount of amlodipine (5mg) dissolved for the half tablets that were tested. The study shows variation in content uniformity and dissolution test for one brand each. All the brands met the pharmacopeia requirements for the tablet weight variation test.

Comparative in-Vitro dissolution study of some sitagliptin generic tablets under biowaiver conditions by UV-Spectroscopy

The objective of this study is to evaluate the bioequivalence of generic sitagliptin tablets from different manufacturers using in-vitro dissolution study under biowaiver conditions through UV Spectroscopy, and compare them with the innovator brand. The dissolution media consisted of three different buffers with varying pH levels, including HCl Buffer pH 2.0, Phosphate Buffer pH 4.0, and Phosphate Buffer pH 7.2. The dissolution process was conducted using a USP type-2 dissolution apparatus with a 900 ml basket. The rotational speed of the paddle was set at 50 RPM, while maintaining a temperature of 37.5°C +/- 2°C. Samples were collected at four different intervals as recommended by the USFDA, which were 15, 30, 45, and 60 minutes. Validation parameters such as Accuracy, Precision, Linearity, LOD, and LOQ were assessed. The dissolution profiles exhibited no significant variability between different brands and within the same brand. Furthermore, the dissolution results of all tablet formulations, including the innovator brand, were analysed using the difference factor (f1) and similarity factor (f2). The findings from this study indicate that both generic brands of sitagliptin tablets meet the USFDA dissolution specifications and can be considered interchangeable.

In-Vitro Dissolution Study of Solid Dispersion Adsorbate of Nateglinide by Eco-Friendly Liquid Chromatography-Tandem Mass Spectrometric Method through Harmonized Approach of White Analytical Chemistry and Analytical Quality by Design

In-Vitro Dissolution Study of Solid Dispersion Adsorbate of Nateglinide by Eco-Friendly Liquid Chromatography-Tandem Mass Spectrometric Method through Harmonized Approach of White Analytical Chemistry and Analytical Quality by Design

Formulation & Evaluation of Anti Migrane Mouth Dissolving Tablet

The objective of this study is to improve the safety, efficacy, and rate of action of the existing molecule by utilising novel techniques to the administration of medication. This will be accomplished by the application of novel approaches. Orally disintegrating pills containing rizatriptan benzoate were made by the direct compression technique in order to provide migraine sufferers with a more expedient manner of gaining relief from their condition. For the purpose of this inquiry, a 32-factororial design method was utilised, and eight different formulations were examined for each of the super disintegrants that were explored. There were a number of tests that were performed on the batches of tablets that were manufactured. These tests included weight variation, hardness, friability, wetting time, invitro dispersion time, drug content, and invitro dissolution. A UV spectrophotometric approach that is easy, sensitive, rapid, accurate, cost-effective, and repeatable was created in order to identify the dose form of Rizatriptan Benzoate tablets. This method was designed in order to determine the dose form. It has been determined that rizatriptan benzoate has the maximum absorbance at a wavelength of 225 nm, and its molar absorption is measured to be 1.619 Ao. According to Beer's law, the application of the law was observed between 1 and 10 μg/ml. In order to validate the conclusions of the investigation, statistical analysis and recovery studies were carried out. In order to validate the method, a number of various criteria were utilised. These criteria included linearity, accuracy, limit of detection (LOD), limit of quantification (LOQ), Sandell's sensitivity, and specificity were among the criteria that were utilised. The practice of determining the regular dosage of Rizatriptan Benzoate in both tablet and bulk forms was found to be one that is accurate and precise via the utilisation of the preferred method. This was identified through the utilisation of the recommended method. A time period ranging from fifteen to thirty seconds was required for the optimised formulation to be distributed throughout the body. Furthermore, it demonstrated a greater water absorption ratio and released 99.60% of the medication over a period of two minutes and fifteen seconds. This was in addition to everything else that it shown.

Cubosomal nanoformulation increase invitro dissolution and anticancer activity of Fisetin in A549 lung cancer cells.

Aim: To prepare fisetin (FIS) cubosomal nanoformulation to increase aqueous solubility and anticancer activity. Methods: Top-down method using glyceryl monooleate (GMO) and Pluronic F-127. Results: Optimized using 2% GMO and 1% Pluronic F-127, reported 93.07nm particle size, 80.10% drug entrapment, and reports more than 50% enhanced in vitro drug release than native FIS. MTT assay reports IC50 Values of FIS 16.59μg/ml and optimized cubosomal FIS nanoformulation (FISCUB) 12.18μg/ml. The colony numbers observed in clonogenic assay for FISCUB were 8.33±0.58 and FIS 11.67±1.15. In flow cytometry study, apoptotic cells in FISCUB and FIS-treated A549 cells were found to be 33.4 and 6.83% respectively. Conclusion: A stable cubosomal nanoformulation of FIS showed enhanced aqueous solubility and anticancer activity.

Comparison of solubility profiles for pioneer and generic monensin premixes in biorelevant simulated intestinal fluid based on shake flask extractions.

In the United States, a generic Type A medicated article product can gain the FDA approval by demonstrating bioequivalence (BE) to the pioneer product by successfully conducting a blood level, pharmacodynamic, or clinical BE study. A biowaiver can be granted based on several criteria, assuming the dissolution of the test and reference products represents the only factor influencing the relative bioavailability of both products. Monensin is practically insoluble in H2O per the USP definition. Previously published data from a comparison study of monensin dissolution profiles from the pioneer product and four generic products using biorelevant media showed that generic monensin products demonstrated different dissolution profiles to the pioneer product in these USP biorelevant rumen media. This follow-up study compared the solubility profiles in simulated intestinal fluid (cFaSSIF, pH 7.5) for the pioneer product and four generic products. The generic monensin products demonstrated different invitro dissolution profiles to the pioneer product in biorelevant media. The differences demonstrated in solubility and dissolution profiles are of concern regarding the potential efficacy of generic monensin in cattle. There are also additional concerns for the potential development of Eimeria resistance in cattle receiving a sub-therapeutic dose of monensin from a less soluble generic product.

Formulation and Evaluation of Pulsatile drug delivery of Albuterol sulphate and Theophylline drugs using modified Pulsincap technology

Albuterol Sulphate and Theophylline are used as anti-asthma agents. The objective of the present investigation was to design develop and evaluate a modified pulsincap drug delivery system of Albuterol Sulphate and Theophylline for the treatment of Asthma. The body of capsule was made insoluble with water by cross linking with formaldehyde. This modified capsule was completely filled with drug with polymer such as HPMCK15M, HPMC K 100M, PVPK-30 to expel the drug after predetermined lag time. A hydrogel plug was inserted in the body of a capsule to obtain desired drug release after a lag time for chronotherapy of asthma. Untreated capsule was attached to the treated body and was released. The drug was exerted to precompression parameter such as Angle of repose, Bulk density, Tapped density, Car’s index Hassner’s ratio. These capsules were subjected to further post formulation studies such as weight variation, drug content, invitro dissolution studies separately. The pre and post formulation parameters were found to be within permissible limit. The mere compatibility of drug, polymer and excipients were determined by Fourier transform infrared analysis (FTIR) and UV-Visible spectroscopy (UV). The results showed that drug was completely compatible with polymer and excipients. In vitro dissolution were carried out by using pH 6 .8 and pH 7.4 buffers. Based on the result obtained F5 Formulation shows good dissolution profile. Higuchi, Hixson crowell. Koresmeyer peppas to evaluate the kinetics and drug release. The drug release follows first order kinetics and the mechanism was found to be NON FICKS DIFFUSION.
 Keywords: Albuterol Sulphate, Theophylline, modified pulsincap drug delivery system, FTIR, Dissolution

Use of physiologically-based pharmacokinetic modeling to understand the effect of omeprazole administration on the pharmacokinetics of oral extended-release nifedipine.

Proton pump inhibitors (PPIs) can affect the release of drugs from their dosage forms invivo by elevating the gastric pH. Our recent clinical study has demonstrated that drug-drug interactions (DDIs) exist between a PPI, omeprazole, and nifedipine extended-release formulations, where systemic exposure of nifedipine was increased in subjects after multiple-dose pretreatment of omeprazole. However, the mechanism of the observed DDIs between omeprazole and nifedipine has not been well-understood, as the DDI may also be mediated through CYP3A4 enzyme inhibition in addition to the elevated gastric pH caused by omeprazole. This study used physiologically-based pharmacokinetic (PBPK) modeling and simulations to investigate the underlying mechanism of these complex DDIs. A formulation exhibiting differences in invitro dissolution across physiological pH range and another formulation where pH does not impact dissolution appreciably (e.g., an osmotic pump) were chosen to characterize the potential impact of pH. The PBPK models incorporated two-stage invitro release profiles via US Pharmacopeia 2 apparatus. PBPK simulations suggest that the elevated gastric pH following multiple-dose administration of omeprazole has a minimal effect on nifedipine pharmacokinetics (PKs), whereas CYP3A4-mediated DDI is likely the main driver to the observed change of nifedipine PKs in the presence of omeprazole. Compared to the osmotic formulation, the slightly increased exposure of nifedipine can be accounted for by the enhanced drug release in the pH-dependent formulation. The reported model-based approach may be useful in DDI risk assessments, product formulation designs, and bioequivalence evaluations.

Smart green spectrophotometric assay of the ternary mixture of drotaverine, caffeine and paracetamol in their pharmaceutical dosage form

Three green and facile spectrophotometric methods were developed for the assay of Petro® components; drotaverine HCl (DRT), caffeine (CAFF), and paracetamol (PAR). The three methods depend on measuring the absorbance of the studied drugs through their ethanolic solution. The first derivative spectrophotometry (FDS) at (Δλ = 10) were good parameters for DRT and CAFF resolution; DRT and CAFF could be well calibrated using FDS at 320 and 285 nm, respectively. PAR could be estimated at 308 nm utilizing the second derivative spectrophotometry (SDS). Method II relies on the double divisor ratio derivative spectroscopy (DDRDS). The first derivative was applied on each drug where they would be assayed at 309, 288, and 255 nm for DRT, CAFF, and PAR, respectively. Method III depends on the mean centering (MCR) technique. DRT, CAFF, and PAR could be determined at 309, 214, and 248 nm, respectively. The concentrations were rectilinear in the ranges of 2–20 µg/mL for DRT, 1.5–15 µg/mL for CAFF, and 2–40 µg/mL for PAR in double devisor and mean centering but PAR from 5 to 40 µg/mL in derivative method. Method validation was performed according to ICH guidelines assured by the agreement with the comparison method. In addition, greenness assessment of the proposed methods was investigated. The application of the proposed method was extended to analyse tablet dosage form and performing invitro dissolution testing.

Formulation and Evaluation of Letrozole Nanosuspension By Probe Sonication Method using Box-behnken Design

Background: Letrozole (LTZ), is an aromatase inhibitor used for the treatment of hormonally positive breast cancer in postmenopausal women. Letrozole is categorized as a BCS class I drug. It has poor water solubility, rapid metabolism and a range of side effects. Objective: Nanosuspension is a technique which enhances the drug's solubility and bioavailability, resulting in a faster start of effect. The present study was aimed, to formulate nanosuspension using probe sonication method for the enhancement of solubility of Letrozole using poloxamer-188 as stabilizer. The formulation scheme was generated by using Box-Behnken design which is a statistical tool of design of experiments (DOE). Results: Total seventeen formulations were performed for letrozole nanosuspension as suggested by Box-Behnken design by employing probe sonication method. The selected formulations are characterized for particle size and zeta potential. The formulations were checked on percentage of bias in between predicted value and observed value and evaluated for drug content and invitro dissolution study. The formulation was optimized using Box-Behnken design based on invitro cumulative drug release. Among all the formulations NS4 (500mg poloxamer-188, 100mg Letrozole and sonication time of 20mints) was considered to be best with minimum Particle size of 923.5nm, Zeta potential value of -28.7mV, 96.36% of drug content and 94.02% of drug release within 2 hours. Solubility was determined by shake flask method. The solubility of pure drug was found to be only 10%. The solubility studies were performed for the optimized formulation of NS4 showed that the solubility has enhanced up to 90% when compared to pure drug. Conclusion: Thus, the present results revealed that Letrozole nanosuspension solubility has enhanced up to 90% when compared to pure drug by using poloxamer-188 as stabilizer.

Formulation and Evaluation of Famotidine Gastroretentive Floating Tablet by Using Biopolymer

HPMC K4M, HPMC K15M, and HPMC K100M polymers are used in this study to make floating tablets of famotidine hydrochloride. Drug Delivery systems that are floating in the stomach have a lower bulk density than gastric fluids, therefore they stay buoyant in the stomach for a lengthy period of time without impacting gastric emptying rate. In the treatment of gastroesophageal reflex disease (GERD) and peptic ulcer (PUD). Famotidine is a histamine H2 receptor antagonist (GERD). Famotidine is an excellent option for a floating drug delivery system because of its short half-life, brief time in the stomach, and repeated doses. Melt-granulation technique was used to make famotidine floating tablets using HPMC K4M, HPMC K15M, and HPMC K100M. In vitro buoyancy, drug polymer compatibility (IR Research), weight fluctuation, hardness, friability, thickness, drug content and invitro dissolution experiments were all performed on the floating tablets. Using in vitro buoyancy and dissolvability experiments, we were able to establish that the micromeritic characteristic were excellent. HPMC K100M-based formulation F4 has an excellent in vitro buoyancy lag time and floating time, and in vitro dissolution investigations demonstrate a 96.78 percent release for 12 hours. As a result of the findings of this research, it can be concluded that famotidine floating tablets provide the potential for longest- term drug delivery and a consequent reduction in dosage frequency. Keywords: Gastroretentive floating tablet, Famotidine, Formulation and Evaluation, Biopolymer

In-Vitro Dissolution Study protocol for various Vaginal Dosage Forms

The vaginal mucosa is well recognized as a route for delivering variety of drugs. Considerable number of anti-fertility drugs have been successfully delivered through vaginal and uterine canals. The goal of this review is to summarize the present clinical state of intravaginal medicines and IUDs, with a prime focus on the available in-vitro dissolution study methods and their importance. At present different vaginal drug delivery systems are available in the market and a few are under clinical trial. The accurate estimation drug release profile of any of such dosage form is primarily depends on the standard dissolution study protocol. The vaginal delivery system is an effective site for local and systemic drug delivery, and a range of innovative formulation strategies are being researched for its development. The concept behind the study is mainly lies on the fact that the standard dissolution protocol may vary based on formulation type, its design and its therapeutic goals.

Stable Solid Dispersion Incorporated Sustained Release Oral Gel of 23 mg Donepezil Hcl

The objective of the present study is to formulate and evaluate stable solid dispersion incorporated sustained release oral gel of donepezil Hcl. Solid dispersions were prepared using HPMC K100M and stearic acid using physical mixture, co-grinding and fusion methods and incorporated into the previously prepared gel bases using sodium CMC and sodium alginate and suitable formulation was optimised. All the formulations were subjected to physicochemical evaluation parameters. Solid dispersions of donepezil were prepared with HPMC K100 and stearic acid by using different methods like physical mixtures, co grinding and fusion method in the ratios of 1:1, 1:2 and 1:3. From the invitro dissolution studies, it was found that SD made by co grinding and fusion method showed sustained release and were selected and incorporated into the gel formulations made of SCMC 4% and sodium alginate 4%. The release studies of solid dispersion incorporated gel SD-HPMC K100M showed (SDG1) 87.55% and (SDG2) 88.9% at 8th hour and SD-stearic acid showed (SDG3) 83.26% and (SDG4) 82.57% at 8th hour. It was concluded that stearic acid solid dispersions incorporated in sodium CMC gels (SDG3) were optimised using short term stability studies with no leakage of drug in comparison to solid dispersions of HPMC K100M in sodium CMC gel l. Physico-chemical evaluation parameters were carried out for optimised formulations and found to be within limits. The optimized SD incorporated gel formulation of donepezil can be an alternative to SR tablet in improving the compliance of the geriatric patients.

Formulation development and evaluation of Orally Disintegrating Tablets Rizatriptan Benzoate

Formulation research is oriented towards safety, efficacy and quick onset of action of existing drug molecule through novel concepts of drug delivery. Orally disintegrating tablets of Rizatriptan benzoate were prepared by direct compression method to provide faster relief from pain to migraine sufferers. About eleven formulations for the present study were carried out. Croscarmellose sodium, Crospovidone and Sodium starch glycolate (SSG) were used as superdisintegrants, while microcrystalline cellulose was used as diluent. The prepared batches of tablets were evaluated for weight variation, hardness, friability, wetting time, invitro dispersion time, drug content and invitro dissolution studies. The formulation containing combination of Croscarmellose sodium and Sodium starch glycolate showed rapid invitro dispersion time as compared to other formulations. The optimized formulation dispersed in 8 seconds. It also showed a higher water absorption ratio and 99.58% of drug is released within 2 minutes.

Colon targeted dosage form of Capecitabine using folic acid anchored modified carbon nanotube: in vitro cytotoxicity, apoptosis and in vivo roentgenographic study

Objective Development of dosage form comprising of Capecitabine loaded carbon nanotubes for its targeted delivery to the colon. Method Single walled carbon nanotubes (SWCNT) were functionalized by -COOH and Chitosan along with Folic acid. Capecitabine was loaded in these SWCNT’s, and the system was analyzed by FTIR, SEM and Raman spectroscopy. Percent drug loading was assessed and the cytotoxicity (COLO320DM and HT29) was verified by using MTT and SRB assay. The apoptosis study was carried out by flowcytometry. The system was enclosed in an enteric coated capsule with pH sensitive polymers and characterized for invitro disintegration, dissolution and invivo roentgenographic studies. Results FTIR, Raman and XRD studies indicated the confirmation of attachments, whereas SEM exhibited size range of 200-500 nm. Drug loading capacity was observed to be 94.63 ± 1.07%. Cytotoxicity studies of Capecitabine and FA–CHI-F-SWCNT-Capecitabine against COLO320DM by using MTT assay showed that FA–CHI-F-SWCNT- Capecitabine exhibited 86.45 ± 0.5788% inhibition whereas pure Capecitabine showed 50.52 ± 0.3106% inhibition. Against HT29, the % inhibition was observed to be 82.76 ± 0.4668% and 56.41 ± 0.2316% respectively for FA–CHI-F-SWCNT-Capecitabine and pure Capecitabine. In case of SRB assay of COLO320DM, the FA–CHI-F-SWCNT-Capecitabine exhibited 89.62 ± 0.4095% inhibition and Capecitabine showed 84.36 ± 0.2559% inhibition, whereas against HT29, FA–CHI-F-SWCNT-Capecitabine showed 81.36 ± 0.2958% inhibition and Capecitabine exhibited 90.62 ± 0.4196% inhibition. Conclusion FA–CHI-F-SWCNT loaded system revealed better cytotoxicity as compared with pure Capecitabine against two different cell lines. Invivo studies revealed that the prepared capsule formulation remained intact in the stomach thereby preventing drug release in the gastric milieu.

ROLE OF FUNCTIONALIZED GUAR GUM IN SOLID DISPERSION OF NON-STEOIDAL ANTI-INFLAMMATORY DRUG

The current investigation was developed to study the role of functionalized guar gum as carrier in solid dispersion of iboprofen. The solid dispersion technique using aminated guar gum would be an effective approach for increasing the solubility and increasing dissolution behaviour of ill fathomable medicament than the native guar gum. The results of FTIR and DSC studies confirmed that there is no chemical interaction or no incompatability between the drug and excipients. The invitro dissolution study was performed for the the prepared formulations. Based on the results SD3 was shown highest drug release 99.41% within 24hrs. Stabiliy study was conducted as per ICH guidelines and the falloutsrevealed that there is no physical or chemical change.it may be concluded that solubility of ibuprofen can br improved by using functionalized guar gum in the solid dispersion, which provides a wide scope for the therapeutic efficiency.

Evaluation of the In-Vitro Dissolution Permeation Systems 1 (IDAS1) as a potential tool to monitor for unexpected changes in generic medicaments in poorly regulated markets

Panama, like most Latin American countries, has insufficient regulatory safeguards to ensure the safety and efficacy of all pharmaceutical products in the market, a situation that results in a two-tier system, where affluent citizens can afford innovator products while poor citizens must consume ‘generics’ of uncertain quality. Given that one lot of each drug product is analyzed every five years during registration while commercial lots are not, and since most products are not bioequivalent but simply copies or similars, there is a concern that commercial and registration lots of these ‘generics’ may not be of the same quality. The objective of this study was to assess the ability of various in vitro quality control tests to detect difference among five amlodipine products available in the Panamanian market: four ‘generics’, made in various countries, and the innovator, made in Germany and used as reference listed drug in Panama (Pan-RLD). The innovator manufactured in the United States (US-RLD) was used to compare the two RLDs. The Content Uniformity test, 30-min Dissolution test and multiple-pH Dissolution Profiles did not show any difference among the products. However, the in vitro dissolution absorption system 1 (IDAS1) showed a statistically significant difference in the amount dissolved between Pan-RLD and three out of the four ‘generics’, and significantly lower permeated amount for all the ‘generics’ compared with Pan-RLD; only US-RLD was similar to Pan-RLD. Thus, IDAS1 showed promise as a potential tool that authorities in weakly regulated markets can use to monitor for possible lot-to-lot product changes, which can help improve the quality of pharmaceutical products available to their entire populations. The significance of the similarity between the innovators made in Germany and the United States and their difference from the ‘generics’ (manufactured in other countries) is not known but deserves investigation.

In-Vitro Dissolution and Characterization of Self-Emulsifying Drug Delivery System of Artemisinin for Oral Delivery

Artemisinin is a compound extracted from Artemisia Annua. Artemisinin is used globally as the first-line antimalarial drug. Despite its high efficacy against the malaria parasite, artemisinin has low bioavailability because it has low solubility in water. This present study was conducted to prepare and characterize the self-emulsifying drug delivery system of artemisinin to increase the dissolution profile of artemisinin. The stability of the resulting emulsion was observed visually for 6 hours. Droplet size, polydispersity index, and zeta potential of the emulsion were measured using Nano Particle Analyzer. The optimum formulation was evaluated with the dissolution test and compared with the artemisinin crystal. Several formulations have good stability of the resulting emulsions where no creaming or flocculation was formed during the observation. Droplet sizes of the resulting emulsions ranged from 114.17-247.93 nm and the polydispersity index of the emulsions ranged from 0.35- 0.56. Zeta potential values of the selected formulations were found in the range of -23.23 - -2.33 mV. Fourier Transform Infrared Spectroscopy spectra of self-emulsifying drug delivery system showed the presence of artemisinin in the formulation with lactone and peroxide peaks. The dissolution of artemisinin in the self-emulsifying drug delivery system was significantly increased compared to artemisinin crystal. Artemisinin was released up to 98,6 %in 150 minutes in self-emulsifying drug delivery system formulation.

Fabrication and Characterization of Surface Engineered Rifampicin Loaded Lipid Nanoparticulate Systems for the Potential Treatment of Tuberculosis: An InVitro and InVivo Evaluation.

The main aim of the present investigation highlights the development of mannose appended rifampicin containing solid lipid nanoparticles (Mn-RIF-SLNs) for the management of pulmonary TB. The developed Mn-RIF-SLNs showed particle size of Mn-RIF-SLNs (479±13nm) which was found to be greater than that of unconjugated SLNs (456±11nm), with marginal reduction in percentage entrapment efficiency (79.41±2.42%). The invitro dissolution studies depicted an initial burst release followed by sustained release profile indicating biphasic release pattern, close-fitting Weibull model having least F-value. The cytotoxicity studies using J774A.1cell line represented that the developed SLNs were non-toxic and safe as compared to free drug. Fluorescence imaging and flow cytometric (FACS) analysis depicted significant (1.79-folds) intracellular uptake of coumarin-6 (fluorescent marker) loaded Mn-C6-SLNs. The invivo pharmacokinetic studies in sprague-dawley rats were performed and Mn-RIF-SLNs showed remarkable enhancement in terms of relative bioavailability (~17-folds) as compared to its drug solution via oral administration. The biodistribution studies revealed higher lung accumulation (1.8-folds) of Mn-RIF-SLNs as compared to the Un-RIF-SLNs. In conclusion, the developed Mn-RIF-SLNs could serve as a promising tool for delivering the drug cargo to the site of infection (lungs) in the treatment of TB.

Optimization and Evaluation of Self-nanoemulsifying Drug Delivery System for Enhanced Bioavailability of Plumbagin.

Plumbagin, a potential bioactive lipophilic molecule, possesses limited solubility and low oral bioavailability. The purpose of the present study was to examine the potential of the self-nanoemulsifying drug delivery system for improving solubility and oral bioavailability of plumbagin. The self-nanoemulsifying drug delivery system was formulated from Capmul MCM (oil), Tween 20 (surfactant), and propylene glycol (cosurfactant). Central composite design was employed as statistical tool to optimize the formulation variables, X1 (oil) and X2 (surfactant: co-surfactant mixture ratio), of the self-nanoemulsifying drug delivery system. The responses studied were droplet size, self-emulsification time, % of drug release in 15 min, and equilibrium solubility. The optimized liquid self-nanoemulsifying drug delivery system was adsorbed on Neusilin US2 and characterized for flow properties, X-ray diffractometry, differential scanning calorimetry, in vitro dissolution, in vivo anti-inflammatory activity, and bioavailability study in Wistar rats, as well as ex vivo permeation study. The droplet size, polydispersity index, self-emulsification time, and equilibrium solubility of the optimized formulation were 58.500 ± 1.170 nm, 0.228 ± 0.012, 17.660 ± 1.520 s, and 34.180 ± 1.380 mg/mL, respectively. Its zeta potential, transmittance value, and cloud point were - 28.200 ± 1.200 mV, 99.200% ± 0.600, and 90 °C, respectively. Drug release was found to be 93.320% ± 1.090. In vivo anti-inflammatory study confirmed more enhanced activity from the self-nanoemulsifying drug delivery system than with pure plumbagin. Pharmacokinetic study in rats revealed that solid self-nanoemulsifying drug delivery system had 4.49-fold higher bioavailability than pure plumbagin. Ex vivo permeation study demonstrated 1.75-fold increased intestinal permeability of the self-nanoemulsifying drug delivery system than pure plumbagin. The developed self-nanoemulsifying drug delivery system is a useful solid platform for improving solubility and oral bioavailability of plumbagin.