Dissolution Profiles Research Articles

Risperidone Pellets, Pycnogenol®, and Glucomannan Gummy Formulation for Managing Weight Gain and ADHD in Autistic Children.

Gummy formulations are defined as gradually or slowly released solid oral dosage forms. Risperidone is an atypical antipsychotic medication used to treat schizophrenia and autism-related irritability. This study presents the development of visually appealing, patient-tailored medicated gummies that act as a novel pharmaceutical form of Risperidone for pediatrics. In this study, two gummy bases were used, one containing Glucomannan and the other containing Gelatin as a gelling agent, where these gummy bases were loaded with coated Risperidone pellets with a controlled release layer. The final products were evaluated for their pH, viscosity, content uniformity, drug content, and dissolution profile. Both formulas showed proper rheology and met content and weight uniformity standards. The release rates for F1 and F2 in the acidic media were 25% and 11%, respectively, after 2 h. At the same time, a full-release profile for Risperidone was noticed in both formulae at pH 6.8 where the release lasts for 24 h. It can be concluded that the chewable semi-solid dosages (gummies) filled with coated pellets are suitable for pediatric patients since pediatrics have drug-related problems which can be solved using high gastro-resistance coated pellets, which also shows a proper release profile for the drug.

In Situ Eutectic Formation in a Polymeric Matrix via Hot-Melt Reactive Extrusion and the Use of Partial Least Squares Regression Modeling for Reaction Yield Determination.

There has been a significant volume of work investigating the design and synthesis of new crystalline multicomponent systems via examining complementary functional groups that can reliably interact through the formation of noncovalent bonds, such as hydrogen bonds (H-bonds). Crystalline multicomponent molecular adducts formed using this approach, such as cocrystals, salts, and eutectics, have emerged as drug product intermediates that can lead to effective drug property modifications. Recent advancement in the production for these multicomponent molecular adducts has moved from batch techniques that rely upon intensive solvent use to those that are solvent-free, continuous, and industry-ready, such as reactive extrusion. In this study, a novel eutectic system was found when processing albendazole and maleic acid at a 1:2 molar ratio and successfully prepared using mechanochemical methods including liquid-assisted grinding and hot-melt reactive extrusion. The produced eutectic was characterized to exhibit a 100 °C reduction in melting temperature and enhanced dissolution performance (>12-fold increase at 2 h point), when compared to the native drug compound. To remove handling of the eutectic as a formulation intermediate, an end-to-end continuous-manufacturing-ready process enables feeding of the raw parent reagents in their respective natural forms along with a chosen polymeric excipient, Eudragit EPO. The formation of the eutectic was confirmed to have taken place in situ in the presence of the polymer, with the reaction yield determined using a multivariate calibration model constructed by combining spectroscopic analysis with partial least-squares regression modeling. The ternary extrudates exhibited a dissolution profile similar to that of the 1:2 prepared eutectic, suggesting a physical distribution (or suspension) of the in situ synthesized eutectic contents within the polymeric matrix.

Improving oral delivery of ciprofloxacin through in situ spray drying and acid counterions

This study explores the application of a novel three-fluid nozzle spray drying technique in formulating in situ ciprofloxacin (CFX) salts for improved oral drug delivery. The used key materials in the study include CFX combined with four different counterions: succinic acid (SA), glutaric acid (GA), adipic acid (AA), and pimelic acid (PA), alongside hydroxypropyl methylcellulose (HPMC) as a matrix agent. The process utilized a three-fluid nozzle spray drying technique to produce CFX salts directly with these acids during the process, creating three types of formulations: pure salts (SALT), solutions of drug and polymer (SOL), and nanoprecipitates of drug within a polymer matrix (SUS). Powder X-ray Diffraction (PXRD) and Scanning Electron Microscopy (SEM) analyses revealed that the formulations predominantly exhibited an amorphous structure with varied particle shapes and sizes. The dissolution profiles of CFX salts show a marked burst release within the initial 5 min, with CFX-GA leading at nearly double the release rate of CFX-AA, after which all formulations rapidly achieve over 90 % dissolution and maintain a stable release up to 30 min. This pattern was attributed to the interactions between the drug salts and HPMC, resulting in a sustained release of CFX. In vivo experiments with rabbits revealed a higher plasma concentration of CFX for CGAH-sus compared to CGAH-sol, highlighting the enhanced bioavailability of the SUS formulation. The amorphous nature of CGAH-sus, with ionization confirmed through Raman spectroscopy, facilitated efficient drug release and absorption in the gastrointestinal tract. This study illustrates the effectiveness of the three-fluid nozzle spray drying method in producing salts with varied physical properties and dissolution profiles, holding potential for advanced oral drug delivery systems.

Modeling and comparison of dissolution profiles for different brands of albendazole boluses

BackgroundAddressing critical veterinary drugs, especially drugs with solubility problems like albendazole, and their implications for therapeutic efficacy, in-vitro dissolution studies can indeed provide valuable insights into how different brands of albendazole boluses perform under standardized conditions, helping to assess their dissolution profiles and potential bioavailability.MethodsSix brands of albendazole 300 mg boluses were collected from December 2020 to May 2021 G.C. The laboratory work was conducted from December 2020 to May 2021 in the National Animal Products and Veterinary Drugs and Feed Quality Assessment Centre (APVD-FQAC) laboratories. The collected brands from government veterinary clinics and private veterinary shops were subjected to model independent and dependent parameters. The dissolution test was conducted according to the USP monograph.ResultsThe study found that none of the six brands met the requirements of the dissolution test, as their API release was less than 80% within the specified 60-minute timeframe according to USP standards. Model independence indicated that only one brand (Alb002 = 3.72) achieved a difference factor of ≤ 15%. The remaining four brands (4/6) did not meet this criterion. However, the similarity factor (f2) revealed that all five brands (5/6) were comparable to the comparator products, with f2 values of \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\ge\\:$$\\end{document}50%. The mean dissolution time results confirmed that three brands (3/6) had the highest dissolution rate and the fastest onset of action. The model-dependent kinetics indicated that the Weibull and Korsemeyer-Peppas models were the best fit for the release of drug substances.ConclusionThe study highlights issues with albendazole boluses’ quality, highlighting the need for national in-vitro dissolution studies. These recommendations could improve quality control, streamline regulatory frameworks, and offer practical, cost-effective methods for evaluating drug efficacy and safety, ensuring veterinary pharmaceuticals meet safety and efficacy standards.

Synthesis of Quarternized Chitosans and Their Potential Applications in the Solubility Enhancement of Indomethacin by Solid Dispersion.

This study was designed to synthesize quarternized chitosans (Q-CS) and explore their potential application in aqueous solubility enhancement of indomethacin (IND), a BCS class-II drug.Three different Q-CS; N,N,N-trimethyl chitosan chloride (TMC), N-(4-N'-methylpyridinylmethyl) chitosan chloride (mPyCS), and N-(4-N',N',N'-trimethylaminobenzyl) chitosan chloride (TmBzCS) were synthesized and characterized through various spectroscopic analysis. Q-CS-based solid-dispersion (SD) composites of IND (Q-CS-IND) were prepared using the spray-drying methodand characterized through Fourier transform infrared (FTIR), scanning electron microscopy (SEM), differential-scanning calorimetry (DSC), and powder X-ray diffraction (P-XRD). The solubility and dissolution profiles of SD-composites of IND were evaluated and compared with physical mixtures (PM). The IND contents were quantified and validated in the composites using UV-Vis spectrophotometer.FTIR and NMR analysis showed the successful preparation of Q-CS. TMC was found with the highest yield (55.13%) and mPyCS with the highest degree of quaternization (DQ) (63.37%). FT-IR analysisof IND-Q-CS composites demonstrated chemical interaction between carbonyl moieties of IND with functional groups of Q-CS. DSC and PXRD analyses demonstrated the transformation of IND in SD compositesfrom crystalline to an amorphous form. All the IND-Q-CS composites were observed with a significant increase in the solubility and dissolution rate of the drug (1996.0µg/min) compared to PM (1306.8µg/min), which is higher than pure IND (791.6µg/min). The contents of IND in TMC, mPyCS, and TmBzCS composites were 97.69-99.92%, 97.66-100.25%, and 97.18-100.11% respectively.Overall, the findings encourage the applications of Q-CS derivatives for increasing IND water solubility and warrant further in vivo biological profiling of IND composites.

Bioequivalence Analysis of Terazosin Hydrochloride Tablets Based on Parallel Artificial Membrane Permeability Analysis.

Parallel artificial membrane permeability analysis (PAMPA) is used to determine the permeability of compounds through concentrated negatively charged phospholipid bilayer barriers. We employed MacroFlux (a scaled-up version of PAMPA) to test the permeation rate of terazosin hydrochloride (TH) tablets and predict in vivo bioequivalence. The dissolution profiles and permeability of one reference formulation, and seven generic TH tablets, were compared. The dissolution profiles of these generic tablets were equivalent to that of the reference drug in four different media. However, the flux and the total permeated amount of some generic TH tablets were below the lower limit of the confidence interval of the original acceptance range in MacroFlux, which implied risk in the bioequivalence test in vivo. We further evaluated potential factors responsible for this discrepancy by µFlux, including active pharmaceutical ingredient (API) permeability and excipient prescriptions. The analysis showed that different properties of API were a main factor leading to biological inequivalence in the MacroFlux assay, while excipient prescriptions did not have an impact on bioequivalence risk. These data indicated that the flux assay may be a helpful as an auxiliary method for predicting bioequivalence of generic drugs and analyze the factors responsible for bioequivalence risk.

The vehicle of administration, feed or water, and prandial state influence the oral bioavailability of amoxicillin in piglets.

Feed and water components may interact with drugs and affect their dissolution and bioavailability. The impact of the vehicle of administration (feed and water) and the prandial condition of weaner piglets on amoxicillin´s oral bioavailability was evaluated. First, amoxicillin's in vitro dissolution and stability in purified, soft, and hard water, as well as release kinetics from feed in simulated gastric and intestinal media were assessed. Then, pharmacokinetic parameters and bioavailability were determined in fasted and fed pigs using soft water, hard water, or feed as vehicles of administration following a balanced incomplete block design. Amoxicillin showed similar dissolution profiles in soft and hard water, distinct from the dissolution profile obtained with purified water. Complete dissolution was only achieved in purified water, and merely reached 50% in soft or hard water. Once dissolved, antibiotic concentrations decreased by around 20% after 24h in all solutions. Korsmeyer-Peppas model best described amoxicillin release from feed in simulated gastric and intestinal media. Feed considerably reduced antibiotic dissolution in both simulated media. In vivo, amoxicillin exhibited significantly higher bioavailability when delivered via water to fasted than to fed animals, while in-feed administration yielded the lowest values. All treatments showed a similar rate of drug absorption. In conclusion, we demonstrated that water and feed components, as well as feed present in gastrointestinal tract of piglets decrease amoxicillin´s oral bioavailability. Therefore, the use of oral amoxicillin as a broad-spectrum antibiotic to treat systemic infections in pigs should be thoroughly revised.

Curcumin- β-Cyclodextrin Molecular Inclusion Complex: A Water-Soluble Complex in Fast-dissolving Tablets for the Treatment ofNeurodegenerative Disorders.

Orally disintegrating tablets (ODTs) have become an excellent choice for delivering drugs as their palatability is greatly improved. In this work, β-cyclodextrin has been used to improve the solubility of curcumin by encapsulating it into the hydrophobic cavity for the treatment of neurodegenerative disorders. The current study aimed to present the design, formulation, and optimisation of fastdissolving oral tablets of curcumin- β-cyclodextrin molecular inclusion complex using a 32-factorial design. The drug-excipient compatibility was studied by FTIR spectroscopy. The inclusion complex of curcumin-β-cyclodextrin was prepared using solvent casting and confirmed using XRD studies. Powder blends were evaluated for flow properties. Tablets prepared by direct compression were evaluated for post-compression parameters. Further, the effect of formulation variables, such as sodium starch glycolate (X1) and Neusilin® ULF2 (X2), on various responses, including disintegration time and dissolution at 2 hours, was studied using statistical models. Post-compression parameters, i.e., hardness (4.4-5 kg/cm2), thickness (3.82-3.93 mm), weight variation (±7.5%), friability (< 1%), wetting time (51-85 seconds) and drug content (96.28- 99.32%) were all found to be within the permissible limits and the disintegration time of tablets with super-disintegrants ranged between 45-58 seconds. The in-vitro dissolution profile of tablets showed that higher SSG and Neuslin® ULF2 levels promoted drug release. For statistical analysis, the 2FI model was chosen. Optimised variables for formulation have been determined and validated with the experimental findings based on the significant desirability factor. The current study reveals the validated curcumin-β-cyclodextrin inclusion complex fastdissolving tablets with SSG and Neusilin® ULF2 to be an ideal choice for effectively treating neurodegenerative disorders.

Enhancing therapeutic effects alginate microencapsulation of thyme and calendula oils using ionic gelation for controlled drug delivery

This study focuses on encapsulating and characterizing essential oils such as thyme and calendula oils, which are known for their therapeutic properties but are limited in pharmaceutical formulations due to their low water solubility and instability, with alginate microspheres. Alginate presents an excellent option for microencapsulation due to its biocompatibility and biological degradability. The ionic gelation (IG) technique, based on the ionic binding between alginate and divalent cations, allows the formation of hydrogel materials with high water content, mechanical strength, and biocompatibility. The microspheres were characterized using FT-IR, SEM, and swelling analyses. After determining the encapsulation efficiency and drug loading capacity, the microspheres were subjected to dissolution studies under simulated digestion conditions. It was observed that the swelling percentage of the microspheres in simulated gastric fluid (SGF) ranged from ∼15% to 100%, while in simulated intestinal fluid (SIF) it ranged from ∼150% to 325%. Thyme oil, with low viscosity, exhibited higher encapsulation efficiency than marigold oil. The highest encapsulation efficiency was observed in A-TO-2 microspheres, while the highest drug loading capacity was observed in A-TO-5 microspheres. During the examination of the dissolution profiles of the microspheres, dissolution rates ranging from 10.98% to 23.56% in SGF and from 52.44% to 63.20% in SIF were observed.

Clinically Relevant Characterization and Comparison of Ryaltris and Other Anti-Allergic Nasal Sprays.

The deposition, residence time, and dissolution profile of nasal suspensions containing corticosteroids play a key role in their in vivo efficacy after administration. However, the conventional methods available to characterize nasal products appear to be unsuitable to exhaustively cover these aspects. The work aims to investigate technological aspects of Ryaltris (mometasone furoate and olopatadine hydrochloride nasal spray) compared to other commercial anti-allergic nasal products, namely, Dymista (azelastine hydrochloride and fluticasone propionate), Nasonex (mometasone furoate), and Avamys (fluticasone furoate). Innovative characterization methods were combined with more traditional approaches to investigate the anti-allergic nasal sprays. These methods applied together allowed to differentiate between the different products and provided a clear picture of the nasal product behavior in terms of drug dissolution and deposition. In particular, the dissolution tests were performed exploiting the Respicell® apparatus, an innovative technique that allows for the investigation of inhalation products. Then, formulation viscosities were considered along with a formulation flow test on an inclined plane. Finally, the intranasal deposition profile of the commercial formulations was determined using a silicon nasal cast. The results highlight in vitro significant differences in terms of viscosity as well as dissolution rate of the nasal products, with Ryaltris showing a higher viscosity and lower flow compared to other products, which, along with a corticosteroid faster dissolution rate than Dymista, suggest a potential advantage in terms of clinical behavior.

Development of a simple and rapid Formulation and evaluation of Metformin HCl extended-release tablets in comparison with Glucophage® XR

Metformin HCl is the first-line therapy for type 2 diabetes. It is available in both immediate-release and extended-release tablet forms, with the extended-release tablet being more beneficial. In this study, 34 formulations using five sustained-release agents, alone or in combination, were evaluated. The granular flowability, angle of repose, bulk Density, tapped Density, compressibility index, and Hausner ratio were assessed. Furthermore, the compressed tablets were tested for appearance, hardness, friability, and in-vitro drug release. Eleven formulations were evaluated for dissolution profiles according to the standards specified in the United States Pharmacopeia. After calculating the similarity factor (f1) and difference factor (f2), eight formulations were identified for further investigation. The combination of xanthan gum and hypromellose (HPMC K100) demonstrated superior results regarding the sustained-release agent amount and tablet appearance. This noteworthy finding led to continuing the study to explore further formulations with different amounts of xanthan gum and Hypromellose K100. As a result, formulation F34 was identified as the optimal choice because of its higher drug-to-polymer ratio. In conclusion, the final formulation is a rapid, cost-effective, and straightforward method due to the less time required for drying, the amount of sustained-release agents, and the number of components.

The Continuous and Reversible Transformation of the Polymorphs of an MGAT2 Inhibitor (S-309309) from the Anhydrate to the Hydrate in Response to Relative Humidity.

Polymorphic control is vital for the quality control of pharmaceutical crystals. Here, we investigated the relationship between the hydrate and anhydrate polymorphs of a monoacylglycerol acyltransferase 2 inhibitor (S-309309). Solvent evaporation and slurry conversion revealed two polymorphs, the hydrate and the solvate. The solvate was transformed into the hydrate by heating. X-ray powder diffraction demonstrated that the hydrate was transformed into an anhydrate via an intermediate state when heated. These crystal forms were confirmed under controlled humidity conditions; the presence of the anhydrate, the intermediate hydrate, or the hydrate depended on the relative humidity at 25 °C. The stoichiometry of S-309309 in water in the hydrate form was 4:1. The hydrates and anhydrates exhibited similar crystal structures and stability. The water of hydration in the intermediate hydrate was 0.1-0.15 mol according to the dynamic vapor sorption profile. The stability and dissolution profile of the anhydrate and hydrate showed no significant change due to similar crystal lattices and quick rehydration of the anhydrate. A mechanism for the reversible crystal transformation between the anhydrate and pseudo-polymorphs of the hydrate was discovered. We concluded that S-309309 causes a pseudo-polymorphic transformation; however, this is not a critical issue for pharmaceutical use.

Optimization and evaluation of modified release solid dosage forms using artificial neural network

This study aims to optimize and evaluate drug release kinetics of Modified-Release (MR) solid dosage form of Quetiapine Fumarate MR tablets by using the Artificial Neural Networks (ANNs). In training the neural network, the drug contents of Quetiapine Fumarate MR tablet such as Sodium Citrate, Eudragit® L100 55, Eudragit® L30 D55, Lactose Monohydrate, Dicalcium Phosphate (DCP), and Glyceryl Behenate were used as variable input data and Drug Substance Quetiapine Fumarate, Triethyl Citrate, and Magnesium Stearate were used as constant input data for the formulation of the tablet. The in-vitro dissolution profiles of Quetiapine Fumarate MR tablets at ten different time points were used as a target data. Several layers together build the neural network by connecting the input data with the output data via weights, these weights show importance of input nodes. The training process optimises the weights of the drug product excipients to achieve the desired drug release through the simulation process in MATLAB software. The percentage drug release of predicted formulation matched with the manufactured formulation using the similarity factor (f2), which evaluates network efficiency. The ANNs have enormous potential for rapidly optimizing pharmaceutical formulations with desirable performance characteristics.

Microbeads produced by prilling/vibration technique: A new way to use polyvinyl alcohol in pediatric and veterinary formulations

Poly(vinyl alcohol) (PVA) is a widely used synthetic polymer and due to its hydrophilicity, biocompatibility, and biodegradability, it is considered a suitable polymer for the formulation of drug delivery systems. In this study, PVA was used in a prilling/vibration technology as a pharmaceutical grade excipient to produce microbeads for oral administration that improve class II drugs' solubility and dissolution rate according to the Biopharmaceutical Classification System (BCS). Specifically, Ibuprofen (IBU) is a weakly acidic drug with low solubility at pH 1.2 and Ketoconazole (KETO), a weakly basic drug characterized by low solubility at pH 6.8. These drugs were selected because of their requirements for specific dosing conditions in children or animals, which often differ from commercially available conventional drugs. The microbeads produced were fully characterized in terms of drug loading, encapsulation efficiency, size, morphology, and drug release experiments were also conducted in a gastric fluid for IBU-loaded microbeads and simulated intestinal fluid for KETO-loaded microbeads. Finally, PVA microbeads were compared with an amorphous solid dispersion (ASDs) of the respective APIs, showing the same increase in solubility and dissolution rate. Therefore, the use of the prilling/vibration technology to produce PVA-based microbeads containing BCS class II drugs improves solubility and dissolution profile, which represent fundamental requirements for good bioavailability. Furthermore, the manufactured microbeads provide a high degree of dosing flexibility, making them suitable for administration in pediatric or veterinary patients with swallowing difficulties and requiring customized dosing.

Establishing Virtual Bioequivalence and Clinically Relevant Specifications for Omeprazole Enteric-Coated Capsules by Incorporating Dissolution Data in PBPK Modeling.

Currently, Biopharmaceutics Classification System (BCS) classes I and III are the only biological exemptions of immediate-release solid oral dosage forms eligible for regulatory approval. However, through virtual bioequivalence (VBE) studies, BCS class II drugs may qualify for biological exemptions if reliable and validated modeling is used. Here, we sought to establish physiologically based pharmacokinetic (PBPK) models, in vitro-in vivo relationship (IVIVR), and VBE models for enteric-coated omeprazole capsules, to establish a clinically-relevant dissolution specification (CRDS) for screening BE and non-BE batches, and to ultimately develop evaluation criteria for generic omeprazole enteric-coated capsules. To establish omeprazole's IVIVR based on the PBPK model, we explored its in vitro dissolution conditions and then combined in vitro dissolution profile studies with in vivo clinical trials. The predicted omeprazole pharmacokinetics (PK) profiles and parameters closely matched the observed PK data. Based on the VBE results, the bioequivalence study of omeprazole enteric-coated capsules required at least 48 healthy Chinese subjects. Based on the CRDS, the capsules' in vitro dissolution should not be < 28%-54%, < 52%, or < 80% after two, three, and six hours, respectively. Failure to meet these dissolution criteria may result in non-bioequivalence. Here, PBPK modeling and IVIVR methods were used to bridge the in vitro dissolution of the drug with in vivo PK to establish the BE safety space of omeprazole enteric-coated capsules. The strategy used in this study can be applied in BE studies of other BCS II generics to obtain biological exemptions and accelerate drug development.

Exploration of Abiraterone acetate loaded Nanostructured lipid carriers for bioavailability improvement and circumvention of fast-fed variability.

Abiraterone acetate (ABA), a biopharmaceutical class IV drug suffers from solubility and permeability pitfalls resulting in limited oral bioavailability and positive food effect, i.e. multi-fold enhancement in drug absorption in the presence of food. This poses difficulties to physicians towards the estimation of dose and dosage regimen required for efficacious therapy of prostate cancer (PCa). Nanostructured lipid carriers (NLC) have demonstrated tremendous outcomes in enhancing the oral bioavailability of various entities along with food effect attenuation. In this study, Quality by design and multivariate analysis was employed for optimization of ABA loaded NLC (ABA NLC). The optimal size, PDI and zeta potential obtained using QbD were 134.6nm, 0.163 and -15.7mV respectively. Ex vivo qualitative and quantitative intestinal permeability studies demonstrated improved traversion of NLC through the intestinal segments. In vitro dissolution profile in biorelevant fast and fed gastric and intestinal media revealed minimal differences for ABA NLC compared to ABA. In vivo pharmacokinetics was performed to decipher the efficacy of ABA NLC in mitigating the food effect of ABA. The studies demonstrated 14.51-fold and 1.94-fold improvement in oral bioavailability during fasted and fed state respectively as compared to free ABA. The absorption mechanism of ABA NLC using chylomicron flow blocking approach conveyed lymphatic uptake as the major mechanism. Cmax fast/fed ratio was 0.9758 whereas, AUC fast/fed ratio was 0.9386, which being nearly equivalent, confirmed the food effect attenuation. Therefore, the results of the study demonstrate optimal pharmacokinetics of ABA NLC and its utility in circumventing the fast fed variability.

Model Independent and Dependent Methods for Dissolution Profiles Comparison: Can we take the Road Less Travelled?

Dissolution testing plays an important role in pharmaceutical development due to its ability to provide critical insight into in vivo performance. Dissolution testing during routine pharmaceutical development can ensure batch-to-batch consistency and helps to ensure that the commercial batches are of representative quality to that of studied in the pivotal clinical studies. For comparing the dissolution profiles, there are multitude of approaches suggested by various regulatory agencies that consist of model independent and dependent approaches. The present review aims to summarize the current understanding of dissolution profile similarity approaches. Dissolution profile comparison approaches suggested by various regulatory agencies were compared and contrasted. Further, detailed procedural aspects were provided for the determination of similarity using model independent and dependent approaches. Model independent approaches such as f2 bootstrap, and Multivariate Statistical Distance (MSD) were portrayed from a practical perspective. Advanced tools such as Bias-Corrected and accelerated (BCa) for f2 bootstrap were discussed in depth. Further, model dependent approaches such as zero order, and Weibull models were discussed from realistic scenarios. Finally, the utility of modeling and simulation approaches such as physiologically based pharmacokinetics model (PBPK) and physiologically based biopharmaceutics model (PBBM) were discussed in the context of their ability and potential to supersede traditional dissolution dissimilarity. Overall, this article acts as a ready-to-use guide for pharmaceutics and biopharmaceutics scientists for effective methodologies for dissolution profile comparison for internal decision-making and regulatory justifications.

A Quality by Design Approach for Optimizing Solid Lipid Nanoparticles of Bedaquiline for Improved Product Performance.

Bedaquiline (BQ) solid lipid nanoparticles (SLNs), which have previously been formulated for parenteral administration, have a risk of patient non-compliance in treating tuberculosis. This research presents a strategy to develop BQ SLNs for oral delivery to improve patient adherence, The upper and lower levels for the formulation excipients were generated from screening experiments. Using 4 input factors (BQ, lecithin, Tween 80, and PEG), a full factorial design from 3 × 2x2 × 2 experiments was randomly arranged to investigate 3 response variables: Particle size distribution (PSD), polydispersity index (PdI), and zeta potential (ZP). High shear homogenization was used to mix the solvent and aqueous phases, with 15% sucrose as a cryoprotectant. The response variables were assessed using a zeta sizer while TEM micrographs confirmed the PSD data. Solid-state assessments were conducted using powdered X-ray diffraction and scanning electron microscopy (SEM) imaging. A comparative invitro assessment was used to determine drug release from an equivalent dose of BQ free base powder and BQ-SLN, both packed in hard gelatin capsules. The sonicated formulations obtained significant effects for PSD, PdI, and ZP. The p-values (0.0001 for PdI, 0.0091 for PSD) for BQ as an independent variable in the sonicated formulation were notably higher than those in the unsonicated formulation (0.1336 for PdI, 0.0117 for PSD). The SEM images were between 100 - 400nm and delineated nanocrystals of BQ embedded in the lipid matrix. The SLN formulation provides higher drug levels over the drug's free base; a similarity factor (f2 = 18.3) was estimated from the dissolution profiles.

Development and Characterization of Lipid Nanoparticles Loaded with Antipsychotic Drugs using Central Composite Design

Background: Fluoxetine and olanzapine combination tablets are available in the market for oral administration in the treatment of depression, but fluoxetine has been shown to have a dose-related side effect due to its high oral dose and ability to undergo excessive first-pass metabolism. Olanzapine has low solubility and low bioavailability. Objective: The objective of this study was to prepare lipid nanoparticles containing fluoxetine and olanzapine to enhance the solubility and dissolution profile of the drugs. Methods: Lipid nanoparticles (LNs) were prepared by high-speed homogenization using the ultrasonication method. Different lipids and surfactants were used to screen out the best lipids, surfactants, and their ratio in the preparation of lipid nanoparticles. Drug and polymer compatibil-ity was examined using FTIR and DSC studies. The formulation was optimized using the central composite design to establish functional relationship between independent variables and respons-es. Optimized batch was characterized using particle size, PDI, zeta potential, % EE, % CDR, and stability. Results: Phase solubility study revealed FLX to have highest solubility in stearic acid and oleic acid, whereas OLZ showed highest solubility in Precirol ATO 5 and oleic acid. Poloxamer 188 was selected on the basis of high entrapment efficiency of the drug. In LNs, no significant interaction between drug and polymer was confirmed by DSC and FTIR. The particle size of optimized batch was found to be 411.5 nm with 0.532 PDI and - 9.24 mV zeta potential. For FLX and OLZ, the %EE and %CDR after 8h were found to be more than 90%. No significant change in %EE and %CDR of the formulation was observed after 4 weeks of storage. Conclusion: Experimental results demonstrated excellent drug entrapment as well as controlled release behavior from optimized LNs of FLX and OLZ at reduced dosage frequency.

Solubility and Dissolution Enhancement of Rosuvastatin Calcium by Using HPMC &amp; Guar Gum Polymers and Formulated into Capsule Dosage Form

The main objective of the current study was to prepare the solid dispersions of Rosuvastatin calcium and formulated into capsule dosage form with the combination of different polymers. Solid dispersions are prepared by fusion method by using combination of polymers in different concentrations such as HPMC and Guar gum. Solid dispersion technique will be selected as an efficient means for improving the solubility, dissolution rate and improves the bioavailability of water insoluble drugs. Solid dispersion of Rosuvastatin by the above mentioned method increases the dissolution rate of Rosuvastatin. These solid dispersions will be evaluated by parameters such as drug content, solubility, X-RD, percentage yield, DSC and in-vitro dissolution profile. The stability study of the formulations as per ICH guideline Q1A in stability chamber both at intermediate and accelerated conditions ascertained that the formulations are stable at wide range of storage conditions.