Biopharmaceutics Classification System Class Research Articles

Solubility-Permeability Interplay of Hydrotropic Solubilization of Piroxicam

: Objectives: In this research paper, an investigation has been made to assess the simultaneous effect of a solubility enhancement approach i.e. hydrotropy on the solubility and apparent permeability of piroxicam. The solubility of piroxicam (PRX) a BCS (biopharmaceutics classification system) class II drug has been increased using a mixed hydrotropy approach. This study is based on identifying the pattern of solubility-permeability interplay and confirming whether every solubility gain results in a concomitant decrease in permeability or permeability remains unaffected. Method: Solid dispersions of PRX were formulated using two hydrotropes viz., sodium benzoate (SB) and piperazine (PP) by solvent evaporation method. A comprehensive 32factorial design was employed to study the effect of hydrotropes on the solubility and permeability of PRX. Subsequently, PRX tablets containing these solid dispersions were formulated and evaluated. Key findings: SB and PP displayed a significant increase in the solubility of PRX ranging from 0.99 to 2.21 mg/mL for F1–F9 batches attributed to the synergistic effect of hydrotropes. However, there is a reduction in PRX permeability with increasing hydrotrope levels. The decline in permeability was notably less pronounced compared to the simultaneous rise in aqueous solubility of PRX. Conclusion: An evident trade-off between permeability and solubility emerged through the mixed hydrotropic solubilisation for PRX. As PRX has generally higher intrinsic permeability, it has been assumed that this permeability loss will not affect the overall absorption of PRX. However, it may affect the absorption of drugs with limited permeability. Therefore, solubility permeability interplay should be investigated during solubility enhancement.

OSMOTIC DRUG DELIVERY SYSTEM OF NICORANDIL: DESIGN AND EVALUATION

Objective: The purpose of the current research was to design a nicorandil formulation with controlled drug release using the principles of osmotic pump technology. Nicorandil is a biopharmaceutical classification system (BCS) class 3 drug, having a shorter plasma elimination half-life and bioavailability of 75 to 80%. Methods: The elementary osmotic pump (EOP) was prepared by coating a cellulose acetate polymer on the prepared core tablet. A 24-factorial design was applied to optimize the parameters for the osmotic tablet. A surface orifice was drilled. Results: Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) results showed that there was no interaction between drugs and excipients. A 24-factorial design was applied to optimize the parameters for the elementary osmotic pump. The optimized batch was characterized for in vitro drug release studies, and the effects of pH, osmotic pressure, and agitation intensity were analyzed. All the batches showed a drug release ranging from 90.48% to 98.78% after 12 hours. There was no change in the drug release pattern at different pHs and agitation intensities. The drug release was found to decrease with the increasing osmotic pressure of the dissolution medium. The results showed that the amounts of sodium chloride and mannitol were positively affecting the drug release, while the plasticizers PEG400 and DBP were not critical. Scanning electron microscopic studies (SEM) showed the integrity and surface morphology of the coating membrane before and after dissolution. The prepared EOP was found to deliver nicorandil at zero-order for up to 12 hours. Conclusion: Nicorandil was developed successfully as a controlled drug delivery during a 12-hour period, with variables optimized by the use of a 24-factorial design.

DEVELOPMENT, OPTIMIZATION AND IN VITRO CHARACTERIZATION OF HALOPERIDOL NANOCRYSTALS USING 32 FACTORIAL DESIGN

Objective: The main aim of the present study was to improve the dissolution rate of Haloperidol nanocrystals and thereby increase their bioavailability. Haloperidol is a typical antipsychotic drug and it is used to treat schizophrenia as well as acute mania and mixed states associated with bipolar disorder. Haloperidol falls into the Biopharmaceutics Classification System (BCS-II) class of drugs (poorly soluble aqueous and highly permeable) and has poor bioavailability. Methods: The present study involves the preparation and optimization of Haloperidol nanocrystals by the anti-solvent precipitation method using Polaxomer407 and polyvinyl pyrrolidone K30 (PVP K30). The prepared nanocrystals were evaluated for various parameters like particle size, zeta potential, % drug content, % yield, surface morphology, drug-excipient compatibility studies (Fourier-transform infrared spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC)), and in vitro dissolution studies. Results: Nine preparations were done and the best preparation amongst them was selected for further studies. F7 preparation containingpolaxomer407 and PVP K30 was selected as optimized preparation based on their evaluation parameters. 32 factorial design was used in the preparation. The particle size of the F7 nanocrystals was 300.2±2.7 nm and the zeta potential-36.3±3.2 mV. The % yield was in the range of 63.62±0.3%-98.21±0.8 %. The drug content of various preparations was found to be in the range of 58.46±0.8%-93.54±0.5 %. In vitro dissolution studies showed the highest % drug release for F7(91.54±0.03%) in 10 h. Conclusion: F7 preparation was found to be having acceptable characteristics and thus selected as optimized preparation.

Development of posaconazole nanocrystalline solid dispersion: preparation, characterization and in vivo evaluation

Objective: Posaconazole (PCZ) is an antifungal drug, which acts by inhibiting the lanosterol-14α-demethylase enzyme. It is a biopharmaceutical classification system class II drug with its bioavailability being limited by poor aqueous solubility. The aim of this study was to improve the oral bioavailability of PCZ by preparing nanocrystalline solid dispersion (NCS). Methods: PCZ-NCS was prepared by a combination of precipitation and high-pressure homogenization followed by freeze-drying. Several different surfactants and polymers were screened to produce NCS with smaller particle size and higher stability. Results: The optimized NCS formulation containing 0.2% Eudragit S100 and 0.2% SLS was found to provide the average particle size of 73.31 ± 4.7 nm with a polydispersity index of 0.23 ± 0.03. Scanning electron microscopy revealed the preparation of homogeneous and rounded particles. Differential scanning calorimetry and X-ray diffraction confirmed crystalline nature of NCS. Nanonization increased the saturation solubility of PCZ by about 18-fold in comparison with the neat drug. Intrinsic dissolution study showed 93% dissolution of PCZ within the first 10 min. In vivo pharmacokinetic study in Wistar rats showed that Cmax and AUC total of PCZ-NCS increased by 2.58 and 2.64-fold compared to the marketed formulation. Conclusion: PCZ-NCS formulation presents a viable approach for enhancing the oral bioavailability of PCZ.

Bioequivalence trials for the approval of generic drugs in Saudi Arabia: a descriptive analysis of design aspects

BackgroundThis retrospective analysis aimed to comprehensively review the design and regulatory aspects of bioequivalence trials submitted to the Saudi Food and Drug Authority (SFDA) since 2017.MethodsThis was a retrospective, comprehensive analysis study. The Data extracted from the SFDA bioequivalence assessment reports were analyzed for reviewing the overall design and regulatory aspects of the successful bioequivalence trials, exploring the impact of the coefficient of variation of within-subject variability (CVw) on some design aspects, and providing an in-depth assessment of bioequivalence trial submissions that were deemed insufficient in demonstrating bioequivalence.ResultsA total of 590 bioequivalence trials were included of which 521 demonstrated bioequivalence (440 single active pharmaceutical ingredients [APIs] and 81 fixed combinations). Most of the successful trials were for cardiovascular drugs (84 out of 521 [16.1%]), and the 2 × 2 crossover design was used in 455 (87.3%) trials. The sample size tended to increase with the increase in the CVw in trials of single APIs. Biopharmaceutics Classification System Class II and IV drugs accounted for the majority of highly variable drugs (58 out of 82 [70.7%]) in the study. Most of the 51 rejected trials were rejected due to concerns related to the study center (n = 21 [41.2%]).ConclusionThis comprehensive analysis provides valuable insights into the regulatory and design aspects of bioequivalence trials and can inform future research and assist in identifying opportunities for improvement in conducting bioequivalence trials in Saudi Arabia.

LIQUID AND SOLID SELF-EMULSIFYING DRUG DELIVERY SYSTEMS (SEDDS) CONTAINING VALSARTAN: STABILITY ASSESSMENT AND PERMEABILITY STUDIES

Objective: Valsartan (VST) is a Biopharmaceutical classification system (BSC) class II active ingredient with a bioavailability of approximately 25% and is utilized to treat high blood pressure (hypertension). This study aimed was to showcase the stability and increase the permeability of VST by developing self-emulsifying drug delivery systems (SEDDS) and solidified SEDDS (S-SEDDS) formulations. Material and Method: The ratios of the components were determined by the pseudo-ternary phase diagram, and the characterization studies were conducted in the previous study. Stability was performed in long-term (25±2˚C, 60±5% relative humidity) and accelerated (40±2˚C, 75±5% relative humidity) conditions. The intestinal permeability of SEDDS formulations was evaluated by Caco-2 cells. Result and Discussion: Formulations for 12 month, droplet sizes were found to be 67.52 ± 5.26 nm and 176.93 ± 17.34 nm for SEDDS of VST (VST-SEDDS) and S-SEDDS of VST (VST-S-SEDDS), respectively. During this period, polydispersity indexes were: VST-SEDDS, 0.56±0.1; VST-S-SEDDS, 0.58±0.05. Both formulations increased VST permeability across Caco-2 cells: VST-SEDDS by 2.32x (powder) and 2.18x (commercial); VST-S-SEDDS by 1.38x (powder) and 1.30x (commercial). The formulation components did not have cytotoxic effects. These results demonstrated that newly developed VST-SEDDS and VST-S-SEDDS formulations with high permeability may be a desirable approach for antihypertensive therapy.

Optimizing Paclitaxel Oral Absorption and Bioavailability: TPGS Co-Coating via Supercritical Anti-Solvent Fluidized Bed Technology.

Supercritical anti-solvent fluidized bed (SAS-FB) coating technology has the advantages of reducing particle size, preventing high surface energy particle aggregation, improving the dissolution performance and bioavailability of insoluble drugs. The poor solubility of Biopharmaceutics Classification System (BCS) class IV drugs poses challenges in achieving optimal bioavailability. Numerous anti-cancer drugs including paclitaxel (PTX) belong to the BCS class IV, hindering their therapeutic efficacy. To address this concern, our study explored SAS-FB technology to coat PTX with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) onto lactose. Under our optimized conditions, we achieved a PTX coating efficiency of 96.8%. Further characterization confirmed the crystalline state of PTX in the lactose surface coating by scanning electron microscopy and X-ray powder diffraction. Dissolution studies indicated that SAS-FB processed samples release over 95% of the drug within 1 min. Moreover, cell transmembrane transport assays demonstrated that SAS-FB processed PTX samples co-coated with TPGS had an enhanced PTX internalization into cells and a higher permeability coefficient compared to those without TPGS. Finally, compared to unprocessed PTX, SAS-FB (TPGS) and SAS-FB processed samples showed a 2.66- and 1.49-fold increase in oral bioavailability in vivo, respectively. Our study highlights the efficacy of SAS-FB co-coating for PTX and TPGS as a promising strategy to overcome bioavailability challenges inherent in BCS class IV drugs. Our approach holds broader implications for enhancing the performance of similarly classified medications.

Assessment of Inter-Individual Pharmacokinetic Variability of Voriconazole Based on Bile Salt Disparities using POP-PK Modeling

Background and Objectives: Voriconazole is a powerful biopharmaceutics classification system (BCS) class II antifungal agent with vast inter-individual pharmacokinetic variability. Bile salts have recently emerged as potential contributors to such variations. Based on population PK modeling and in-vitro biorelevant dissolution investigations, the current study intends to evaluate the inter-individual variability of voriconazole in pediatrics. Methods: All models were developed using PK-Sim software. A simulated population consisting of 100 pediatric individuals was established following the baseline model development. Further, experimentally obtained in-vitro dissolution data of voriconazole based on the bile salt differences representing different pediatric age groups were incorporated into a qualified pediatric model. Simulated plasma concentration-time profiles were then evaluated by comparing model-predicted parameters with that of the baseline model to draw inferences. Result: Each model was created and validated successfully. The pediatric subjects were shown to have larger inter-individual variability than adult subjects. Additionally, simulations based on individual parameter estimations from the final model showed that after administering a 4 mg/kg peroral dose of voriconazole, the anticipated Cmax values of the adult model were within a two-fold range compared to that of the pediatric model. However, upon comparison, the model-predicted population pk profiles of children, infants, and neonates showed minimal variations in the Cmax values. Conclusion: In pediatrics, voriconazole inter-individual variability was significantly influenced by the concentration of gut bile salts. Furthermore, the present research can be carried forward along with population PK modeling and sufficient clinical data for dose recommendations in special populations as well as in diseased conditions.

Solubility Enhancement of Poorly Water-Soluble Aceclofenac by Amalgamation Micronization and Solid Dispersion Techniques

Aceclofenac is a poorly aqueous soluble Biopharmaceutical Classification System (BCS) class II drug that has bioavailability problems after oral administration due to low aqueous solubility. There are numerous solubility modification approaches and they also have process limitations. Hence, the present research work aims to use two different solubility enhancement techniques (Micronization with Solid dispersion) simultaneously to counter individual limitations of techniques. The micronization technique increases the solubility of pure aceclofenac through increasing particle surface area, but it produces charged micronized material, leading to segregation and clumping of micronized material. Hence, micronized material handling during dosage form manufacturing is quite difficult. In the present research work, aceclofenac material is micronized by air jet mill to produce materials of below 25 μm size ranges. This micronized aceclofenac material is further encapsulated in a solid dispersion technique to produce amorphous aceclofenac materials. Solid dispersion of micronized aceclofenac was prepared by various techniques like physical kneading, solvent evaporation, melting and a combination thereof using different polymers (Polyox 301, HPMC, cetostearyl alcohol and glyceryl behenate). The prepared solid dispersion formulation (SD-31, SD-22, SD-23 and SD-30) exhibited an increase in the dissolution of aceclofenac as compared to pure aceclofenac. Various characterization techniques (Differential scanning calorimetry (DSC), X-ray Diffraction (XRD) and scanning electron microscope (SEM)) also reveal that aceclofenac crystallinity is significantly minimized in Solid dispersion formulation of SD-31, SD-22, SD-23 and SD-30. This selected solid dispersion (SD-31 and SD-22) also exhibited good stability (Photostability and stability at 40°C/75% RH after 3 months).

Formulation Development and Evaluation of Montelukast Sodium Paper Tablets for Enhanced Drug Release

In this study, the technique of paper-based tablets was evaluated for solubility enhancement of montelukast sodium (MS), an anti-asthmatic, Biopharmaceutical Classification System (BCS) class II medication. Initially, the potential for compressing regular paper into tablets was rigorously examined. Results demonstrated that paper may be utilised to make tablets, regardless of type of the paper utilized. The medicinal quality was satisfactory; and entire tablets of the batch met the Indian Pharmacopeia’s criteria. Compressing drug-loaded paper resulted in the formation of drug-loaded tablets. The MS loaded tablets prepared using kitchen roll paper delivered the best results. The tablet was disintegrated in 27 seconds, and drug release of MS was enhanced by 1.88 folds. The tablets were sufficiently hard, and they did not get broken during friability studies. Also, the tablets passed the other evaluation parameters. These paper tablets were also stable under accelerated storage conditions.

Improving the equilibrium solubility of Nateglinide by synthesizing a novel Nateglinide co-crystal with a single-crystal structure

Nateglinide (NTG) is clinically used to treat type II diabetes. NTG is a Biopharmaceutics Classification System class II drug and is thus almost insoluble in water, limiting its oral bioavailability. The solubility of drugs can be increased through various methods; however, these methods have several limitations. Therefore, this study used solvent evaporation combined with the ultrasonic method to prepare an NTG-isonicotinamide (INA) co-crystal to improve the solubility of NTG and characterized the co-crystal using scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, single-crystal X-ray diffraction (SCXRD), and Fourier transform infrared spectroscopy. The SCXRD results demonstrate that the newly formed crystal material belongs to the P21 monoclinic crystal system. A single crystal was formed by NTG and INA in a stoichiometric ratio of 2:2; the crystallographic information is as follows: a = 8.9552 Å, b = 12.6413 Å, c = 21.5877 Å, α=90°, β=98.463 (6)°, γ=90°, Z = 4, R1=0.0712, and wR2=0.1284. The equilibrium solubility of the co-crystal was more than twice that of NTG, suggesting that it is suitable for further research on its bioavailability and improvement in clinical application.

In Vivo Predictive Dissolution and Biopharmaceutic-Based In Silico Model to Explain Bioequivalence Results of Valsartan, a Biopharmaceutics Classification System Class IV Drug.

The purpose of this study was to predict the in vivo bioequivalence (BE) outcome of valsartan (VALS, BCS class IV) from three oral-fixed combination products with hydrochlorothiazide (HCTZ, BCS class III) (Co-Diovan® Forte as reference and two generic formulations in development) by conducting in vivo predictive dissolution with a gastrointestinal simulator (GIS) and a physiologically based biopharmaceutic model (PBBM). In the first BE study, the HCTZ failed, but the VALS 90% CI of Cmax and the AUC were within the acceptance limits, while, in the second BE study, the HCTZ 90% CI of Cmax and the AUC were within the acceptance limits, but the VALS failed. As both drugs belong to different BCS classes, their limiting factors for absorption are different. On the other hand, the gastrointestinal variables affected by the formulation excipients have a distinct impact on their in vivo exposures. Dissolution tests of the three products were performed in a GIS, and a PBBM was constructed for VALS by incorporating in the mathematical model of the in vitro-in vivo correlation (IVIVC) the gastrointestinal variables affected by the excipients, namely, VALS permeability and GI transit time. VALS permeability in presence of the formulation excipients was characterized using the in situ perfusion method in rats, and the impact of the excipients on the GI transit times was estimated from the HCTZ's in vivo results. The model was able to fit the in vivo BE results with a good prediction error. This study contributes to the field by showing the usefulness of PBBM in establishing in vitro-in vivo relationships incorporating not only dissolution data but also other gastrointestinal critical variables that affect drug exposure in BCS class IV compounds.

Lack of Effect of Antioxidants on Biopharmaceutics Classification System (BCS) Class III Drug Permeability

The addition of antioxidants to pharmaceutical products is a potential approach to inhibit nitrosamine formation, particularly in solid oral dosage forms like tablets and capsules. The objective was to assess the effect of ten antioxidants on the permeability of four Biopharmaceutics Classification System (BCS) Class III drugs. Bi-directional drug permeability studies in the absence and presence of antioxidants were performed in vitro across MDCK-II monolayers. No antioxidant increased drug permeability, while the positive control sodium lauryl sulfate always increased drug permeability. Results support that any of the ten antioxidants, up to at least 10 mg, can be added to a solid oral dosage form without modulating passive drug intestinal permeability. Additional considerations are also discussed.

Third-Generation Solid Dispersion Through Lyophilization Enhanced Oral Bioavailability of Resveratrol.

Resveratrol (RES) is a biopharmaceutical classification system (BCS) class II compound with low solubility and high permeability. Several strategies have been explored to overcome the low bioavailability of RES, making the formation of solid dispersions (SDs) one of the most promising. This study aimed at the development of a RES third-generation SD prepared by lyophilization as a strategy to improve RES solubility, dissolution, and oral bioavailability. Eudragit E PO was selected as the hydrophilic carrier in a 1:2 (RES:carrier) ratio, and Gelucire 44/14 as the surfactant, at 16% (w/w) of RES. Differential scanning calorimetry (DSC), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), polarized light microscopy (PLM), X-ray powder diffraction (XRPD), and particle size distribution (Morphologi 4 Malvern) were used for solid-state characterization and to confirm the conversion of RES to the amorphous state in the SD. Third-generation SD presented an 8-, 12-, and 8-fold increase of RES solubilized compared to pure RES at pH 1.2, 4.5, and 6.8, respectively, and a 10-fold increase compared to the physical mixture (PM), at pH 6.8, after 24 h. In the gastric environment, the dissolution rate of third-generation SD and PM was similar, and 2-fold higher than pure RES after 30 min, while at pH 6.8, third-generation SD presented approximately a 5-fold increase in comparison to pure RES and PM. Third-generation SD presented higher in vitro intestinal permeability compared to its PM and second-generation SD (without Gelucire 44/14). A 2.4 and 1.7-fold increase of RES permeated, respectively in Caco-2 and Caco-2/HT2-MTX models, was obtained with third-generation SD compared to PM, after 3 h. Third-generation SD allowed a 3-fold increase of RES bioavailability compared to second-generation SD, after oral administration of 200 mg/kg of RES to Wistar rats. Enhanced RES oral bioavailability was obtained not only by solubility and dissolution improvement, but also by the interference of Gelucire 44/14, with RES metabolism, and inhibition of P-gp-mediated efflux. The presence of excipients like Gelucire 44/14 in the SD allows for greater bioavailability of orally administered RES, making it easier to obtain some of the physiological benefits demonstrated by this molecule.

Characterization and In vitro Dissolution Assessment of Pitavastatin-polyvinyl Pyrrolidone and Kollicoat®IR Solid Dispersions Prepared by Solvent Evaporation and Fusion Methodologies

Pitavastatin (PTV) is a potent lipid lowering drug that acts on hepatocytes by blocking the 3-hydroxy-3- methylglutaryl-CoA reductase enzyme. As a Biopharmaceutical Classification System (BCS) Class II drug, PTV possesses very low water solubility; hence, poor bioavailability leads to poor drug delivery to the target organ. The study aims to develop various PTV solid dispersion (SD) formulations and to investigate the release profile of PTV SD systems. Different PTV physical mixing and SD formulations were prepared using polyvinylpyrrolidone (Kollidon®90F) and Kollicoat®IR hydrophilic polymers by fusion and solvent evaporation approaches. The efficacy of the formulations was evaluated by in vitro PTV release studies. Subsequently, the characterization of SD formulations was performed using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The in vitro release studies confirmed that all the developed formulations showed a comparatively better release percentage (75.31–98.45%) than the pure PTV (61.76%) after 60 min. Additionally, the outcomes showed that raising the concentration of both polymers improved PTV's ability to dissolve. In comparison to physical mixing formulations, SD formulations made using fusion and solvent evaporation processes performed better during dissolution. The TGA, DSC, and FTIR studies confirmed that the tested SD formulations (1:2, 1:3 ratios) were stable at high temperatures with a reduction in crystallinity and no notable interaction between the drug and polymers. The SEM analysis showed that the PTV was evenly spread out in the carriers and that the crystal-like structure of the PTV had changed into an amorphous form. Bangladesh Pharmaceutical Journal 27(1): 37-50, 2024 (January)

Formulation Development and Assessment of Solid Dispersion and Hydrotropy for BCS Class II Drug Solubility Enhancement

Aim: This study aimed to evaluate the potential of different hydrophilic polymers to increase Arteether's water solubility. Background: Arteether is classified as a class II biopharmaceutical in the Biopharmaceutical Classification System (BCS), with low water solubility (17 g/mL) and dissolution rate, resulting in poor bioavailability. Objective: The goal of this research is to improve the water solubility of Arteether (ART) by using a solid dispersion and hydrotropic approach with a variety of carriers, such as PEG-6000 PVP K-30, Poloxamer- 188, Poloxamer-407, HPMC E 15LV, HPMC K-100M, sucrose, and mannitol, sodium benzoate, sodium citrate, Urea, nicotinamide, and beta-cyclodextrin. Methods: Melting and evaporation methods were used to make the solid dispersion. Instrumental examinations, including XRD, DSC, FTIR, and SEM, confirmed any physical changes caused by the interaction of ART and carriers. Results: The most significant increase in water solubility of Arteether was discovered with CD: PEG600:Pol -407, and the highest enhancement in solubility was 67 times. While 37.34 times and 49 times increase in solubility was observed at 1:4.3:3.7 weight ratio of AE: PEG-6000:Poloxamer-407 40 percent mix of nicotinamide, respectively. The in vitro results show that ART's dissolution rate in the solid dispersion system was dramatically reduced compared to pure drug. This might be because of the drug's enhanced wettability, dispersion ability, and transition from crystalline to amorphous form. Compared to the ART itself, the permeability of Arteether from solid dispersion was increased up to 7 times. However, the permeability of solid cyclodextrin dispersion was extremely low, just 4.42 times. This may be due to the drug encapsulation in the cyclodextrin cavity. Conclusion: This research successfully developed and optimized various polymer and solubility enhancement approaches for Arteether, resulting in increased water solubility, which may improve Arteether's oral bioavailability. The findings of this study might be utilized to develop an oral dosage of Arteether with enhanced bioavailability.

Characterization and Improvement Dissolution Profile of the Hydrochlorothiazide-β-Cyclodextrin Inclusion Complex using Kneading Method

Hydrochlorothiazide is a drug antihypertensives are classified into Biopharmaceutics Classification System (BCS) class IV, so required technique formulation to improve solubility, one of them with complex inclusion. The inclusion complex was prepared with a kneading method with a comparison amount of hydrochlorothiazide - β- cyclodextrin 1:1 (F1) mol, 2:1 (F2) mol, and a physical mixture prepared in a ratio of 1:1 mol. This research aims to see the effect of complex formation inclusion on dissolution rate and characteristics of physicochemical properties of hydrochlorothiazide. Complex inclusions formed are characterized by scanning electron microscopy (SEM), and infrared spectrophotometer (FT-IR). X-ray diffraction, differential scanning calorimetry (DSC), and dissolution profiles. Characterization of physicochemical results analysis diffraction X-rays show that powder complex inclusion hydrochlorothiazide with β-cyclodextrin experiences decline peak intensity approaches a more amorphous nature. Characterization results FT-IR analysis shows No interaction chemistry exists between hydrochlorothiazide β-cyclodextrin. SEM analysis shows morphology substance active Already coated with β- cyclodextrin. DSC analysis shows a decline in enthalpy of the complex inclusions that indicate physical interactions form a simple eutectic mixture. Research results show that complex inclusion hydrochlorothiazide - β-cyclodextrin can repair characteristic physicochemical and can increase hydrochlorothiazide dissolution profile in a way significant (p<0.05) compared with powder The physical mixture with the highest dissolution results was shown by the F1 inclusion complex (82.843 %).

Aerosolizable Pyrazinamide-Loaded Biodegradable Nanoparticles for the Management of Pulmonary Tuberculosis.

Background: Pyrazinamide is a Biopharmaceutical Classification System class III antibiotic indicated for active tuberculosis. Methods: In the present work, pyrazinamide-loaded biodegradable polymeric nanoparticles (PNPs) based dry powder inhaler were developed using the double emulsion solvent evaporation technique and optimized using design of experiments to provide direct pulmonary administration with minimal side effects. Batches were characterized for various physicochemical and aerosol performance properties. Results: Optimized batch exhibited particle size of 284.5 nm, % entrapment efficiency of 71.82%, polydispersibility index of 0.487, zeta potential of -17.23 mV, and in vitro drug release at 4 hours of 79.01%. Spray-dried PNPs were evaluated for drug content, in vitro drug release, and kinetics. The particle mass median aerodynamic diameter was within the alveolar region's range (2.910 μm). In the trachea and lung, there was a 2.5- and 1.2-fold increase in in vivo deposition with respect to pure drug deposition, respectively. In vitro drug uptake findings showed that alveolar macrophages with pyrazinamide PNPs had a considerably higher drug concentration. Furthermore, accelerated stability studies were carried out for the optimized batch. Results indicated no significant change in the evaluation parameters, which showed stability of the formulation for at least a 6-month period. Conclusion: PNPs prepared using biodegradable polymers exhibited efficient pulmonary drug delivery with decent stability.

Formulation and Characterization of Mefenamic Acid Self Nanoemulsifying Drug Delivery System (SNEDDS) Preparations

Mefenamic acid is included in BCS (biopharmaceutical classification system) class II, namely high permeability and low solubility. This research aims to obtain a good formula for oleic acid oil, tween 80, and PEG 400 according to the characterization test of emulsification time, % transmittance, drug loading, globule size, and zeta potential. This research was an experimental study by formulating mefenamic acid in the form of SNEDDS which was made 1 formula was made in the form of SNEDDS with the composition of oleic acid, tween 80, and PEG 400 and characterization tests were carried out for emulsification time, % transmittance, drug loading, globule size, zeta potential. The yield of the oleic acid formula is 1%, tween 80 is 8%, and PEG 400 is 1%. The emulsification time characterization test resulted in 17 seconds, % transmittance of 97%, drug loading of 179.81 mg, globular size of 85.8 nm and zeta potential of -1.6 mV.

Formulation, Development, and Characterization of Carboxymethyl Chitosan Triggered Calcium Carbonate Hybrid Microspheres for Sustained Delivery of Quetiapine: In-vitro and Ex-vivo Studies

Quetiapine (QTP) is a moderately water-soluble biopharmaceutical classification system (BCS) class II antipsychotic drug used to treat schizophrenia. Carboxymethyl chitosan (CMC) microspheres were prepared using a co-precipitation approach. The Quetiapine was translocated to the brain through a nasal route using carboxymethyl chitosan-calcium carbonate (CMC-CaCO3) hybrid microspheres. During this process, optimization controlled the size of the microspheres by controlling the volume of solution, precipitating agent, and concentration ratios of the precursors. The optimized batch showed a narrow size distribution with high stability in the dispersed phase as characterized by dynamic light scattering. Preliminary characterization revealed crosslinking formation between the carboxymethyl groups of chitosan and the CaCO3 may be responsible for the spherical structure. The preliminary evaluations were done with Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), and UV visible spectroscopy (UV-Vis). The surface morphology was assessed by scanning electron microscopy that showed the microscale range of the spherical-shaped particles. The ex-vivo mucoadhesive studies suggested a high binding affinity toward mucin, having a sustained release effect for up to 8 h.