Biopharmaceutics Classification System Research Articles

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.

Key Challenges, Influencing Factors, and Future Perspectives of Nanosuspensions in Enhancing Brain Drug Delivery.

Many brain diseases pose serious challenges to human life. Alzheimer's Disease (AD) and Parkinson's Disease (PD) are common neurodegenerative diseases that seriously threaten human health. Glioma is a common malignant tumor. However, drugs cannot cross physiological and pathological barriers and most therapeutic drugs cannot enter the brain because of the presence of the Blood-brain Barrier (BBB) and Blood- -brain Tumor Barrier (BBTB). How to enable drugs to penetrate the BBB to enter the brain, reduce systemic toxicity, and penetrate BBTB to exert therapeutic effects has become a challenge. Nanosuspension can successfully formulate drugs that are difficult to dissolve in water and oil by using surfactants as stabilizers, which is suitable for the brain target delivery of class II and IV drugs in the Biopharmaceutical Classification System (BCS). In nanosuspension drug delivery systems, the physical properties of nanostructures have a great impact on the accumulation of drugs at the target site, such as the brain. Optimizing the physical parameters of the nanosuspension can improve the efficiency of brain drug delivery and disease treatment. Therefore, the key challenges, influencing factors, and future perspectives of nanosuspension in enhancing brain drug delivery are summarized and reviewed here. This article aims to provide a better understanding of nanosuspension formulation technology used for brain delivery and strategies used to overcome various physiological barriers.

Study of celecoxib dissolution process in the mixtures of ethanol and propylene glycol at different temperatures

ABSTRACT Categorised as a nonsteroidal anti-inflammatory drug targeting the COX-2 enzyme over COX-1, celecoxib (CXB) demonstrates high membrane permeability and low aqueous solubility, placing it in class II of the biopharmaceutical classification system. Therefore, comprehension of its solubility behaviour under different configurations is desirable. The current study explores CXB solubility in propylene glycol and ethanol binary mixtures by varying temperature and cosolvent concentration, using the shake-flask method followed by spectroscopy analysis. The results show increased solubility of CXB in this mixture as ethanol mass fraction and temperature increase. Several cosolvency models were used to correlate data, including van't Hoff, Jouyban-Acree, Jouyban-Acree-van't Hoff, and mixture response surface/modified Wilson models. The mathematical models’ accuracy was investigated through mean relative deviation. The Gibbs and van't Hoff equations were employed to establish the thermodynamic features of CXB dissolution.

Enhancing the solubility of carbamazepine using ionic liquids: An experiment and theoretical calculation

This work investigates the solubility and dissolution mechanism of the insoluble drug, carbamazepine (CBZ), classified as class II drug in the Biopharmaceutical Classification System, in environmentally friendly solvent ionic liquids (ILs). The COSMO-RS model is used to identify suitable ILs for solubilizing CBZ. Experimental data of six ILs confirms the accuracy of the model, validating its usefulness for IL selection. The solubility of CBZ is influenced by both the anionic structure and temperature. Cytotoxicity tests on HUVEC and GES-1 cells show that all ILs are safe for CBZ dissolution. Based on solubility and toxicity data, [EMIM][Ac] is determined to be the optimal IL.The dissolution mechanism of CBZ in ILs is explored using the σ-profile calculated from the COSMO-RS model and quantum chemical (QC) analysis. ILs with anions that have effective hydrogen bond (HB) acceptability ([Ac]-) are found to be the most efficient solvents for CBZ solvation. ILs with longer alkyl chains in the imidazole cations exhibit reduced polarity, increasing their affinity with CBZ. Therefore, [EMIM][Ac] is the superior IL choice due to its moderate polarity in [EMIM]+ and ideal cationic characteristics with long alkyl chains, along with the strong HB acceptability of [Ac]- anions. The findings have significant implications for choosing appropriate solvents, namely ionic liquids, for CBZ, as well as for selecting solvents with comparable structures for other medicines.

Optimization of Nanoemulsion Formula Containing Erythromycin with VCO and Varying Concentrations of Tween-80 and PEG-400

Erythromycin, a macrolide antibiotic is classified into Biopharmaceutical Classification System (BCS) class II which has low solubility in water. The low solubility corresponds to the bioavailability in the blood. One strategy to increase the solubility of Erythromycin is the formulation of erythromycin in nanoemulsion. This research aims to form nanoemulsion using the PIT (Phase Transition Temperature) method for obtaining the optimum formula of erythromycin nanoemulsion using virgin coconut oil (VCO) can be found with varying concentrations of Tween 80 surfactant and PEG 400 cosurfactant. The selection of the optimum formula was assisted by Design Expert software with the Factorial design method 22. The basis for determining the optimum formula is based on the results of organoleptic characterization tests, adsorption efficiency (%EE), percent transmittance, viscosity test, pH test, and stability test. The optimum formula was nanoemulsion which had a concentration of Tween 80 25% and PEG 400 25% as a desirability value of &lt;1. The results of the optimum formula showed that the particle size was 170.6±12.8594 nm, polydispersity index (PDI) 0.403±0.04406, and zeta potential -8.8667±0.25697 mV and had an appropriate stability without phase separation during stability test.

Enhancement of Solubility by Hydrotropic Techniques of Lercanidipine HCl: In-situ Nasal Gel Development

Lercanidipine HCl is a novel, third-generation, potent, vasoselective 1, 4- dihydropyridine calcium channel antagonist and a Biopharmaceutical Classification System (BCS) class II drug that aids in preventing hypertension. The final aim of the present work was to promote the solubility of lercanidipine HCl via hydrotrophy and then include it in the in-situ gel formulation. This enhancement of drug solubility was carried out by using citric acid as a hydrotropic agent. Simultaneously, using a mixture of two polymers, namely Poloxamer 407, a thermosensitive polymer with reversible thermal characteristics. Carbopol 940P is a high-viscosity builder exploited for developing in-situ gel. The optimization of preliminary batches of mixtures of both polymers was highly accepted by using 32 factorial designs. F4 was found to be highly optimized, according to all the evaluation parameters and Poloxamer 407 (18% w/v) and Carbopol 940P (0.2% w/v), with drug release of 93.23%. Goat mucosa ex-vivo investigation yielded a value of 79.14% flux at 6 hours. According to ICH guidance, the in-situ Lercanidipine HCl gel has turned up to be stable following a 6-month stability investigation. Thus, the subsequent thermoreversible in-situ gel was scouted to act as a potent nasal distributor with greater bioavailability and patient compliance for the nasal medication.

Formulation Development and Evaluation of Ticagrelor Oral Dispersible Tablets by Using Co-processed Superdisintegrants

Ticagrelor is a contemporary anti-platelet drug that inhibits the aggregation of platelets by blocking the adenosine phosphate (ADP) receptors of the subtype P2Y12; generally utilized in patients who have a previous history of myocardial infarction or with acute coronary syndrome to prevent occurring of myocardial infarction, cardiovascular death and stroke in future. This study focuses on the development of formulation development &amp; assessment of an oral dispersible tablet of ticagrelor, a Biopharmaceutical Classification System (BCS) class 4 drug, by using the co-processed superdisintegrants to enhance drug dissolution and bioavailability. Wet granules with different concentrations of co-processed superdisintegrants developed the tablets. This study includes seven formulations that were formulated using the different selected excipients. The various batches were assessed for physical characteristics, disintegration, dissolution studies, hardness and friability. In-vitro dissolution investigations were conducted for formulations. S1 to S7 at time points 5, 15 and 30 minutes. According to the results of the formulation S7 was discovered to be the optimum formulation, as shown 102.89% drug release at 5 minutes and a disintegration time of 16 seconds. Thus, it appears that S7 is the most suitable formulation of ticagrelor oral dispersible tablet in order for enhanced bioavailability.

Formulation Development and Evaluation of Ticagrelor Oral Dispersible Tablets by Using Co-processed Superdisintegrants

Ticagrelor is a contemporary anti-platelet drug that inhibits the aggregation of platelets by blocking the adenosine phosphate (ADP) receptors of the subtype P2Y12; generally utilized in patients who have a previous history of myocardial infarction or with acute coronary syndrome to prevent occurring of myocardial infarction, cardiovascular death and stroke in future. This study focuses on the development of formulation development &amp; assessment of an oral dispersible tablet of ticagrelor, a Biopharmaceutical Classification System (BCS) class 4 drug, by using the co-processed superdisintegrants to enhance drug dissolution and bioavailability. Wet granules with different concentrations of co-processed superdisintegrants developed the tablets. This study includes seven formulations that were formulated using the different selected excipients. The various batches were assessed for physical characteristics, disintegration, dissolution studies, hardness and friability. In-vitro dissolution investigations were conducted for formulations. S1 to S7 at time points 5, 15 and 30 minutes. According to the results of the formulation S7 was discovered to be the optimum formulation, as shown 102.89% drug release at 5 minutes and a disintegration time of 16 seconds. Thus, it appears that S7 is the most suitable formulation of ticagrelor oral dispersible tablet in order for enhanced bioavailability.

Effects of Functional Biomaterials on the Attributes of Orally Disintegrating Tablets Loaded with Furosemide Nanoparticles: In Vitro and In Vivo Evaluations.

Furosemide (FUR) is a diuretic used to relieve edema, congestive heart failure, cirrhosis, end-stage renal disease, and hypertension. FUR is a class IV according to the Biopharmaceutics Classification System. It is practically insoluble in water. This study aimed to optimize and formulate porous orally disintegrating tablets (ODTs) prepared by sublimation and loaded with FUR nanoparticles prepared by using a planetary ball mill. Different functional biomaterials called stabilizers were used to stabilize the nanoparticle formula. Pluronic F-127 was the optimum stabilizer in terms of particle size (354.07 ± 6.44), zeta potential (-25.3 ± 5.65), and dissolution efficiency (56.34%). The impact of the stabilizer concentration was studied as well, and a concentration of 3% showed the smallest particle size (354.07 ± 6.44), best zeta potential value (-25.3 ± 5.65), and percentage of dissolution rate (56.34%). A FUR-loaded nanoparticle formula was successfully prepared. The nanoparticle formula was stabilized by using 3% pluronic F-127, and 3% was chosen for further study of the incorporation into oral disintegration tablets prepared by the sublimation technique. The impact of the matrix sublimating agent and superdisintegrant on the ODTs' attributes (in vitro disintegration, wetting time, and in vitro dissolution efficiency) was studied using 32 full factorial designs. In vivo, the diuretic activity was tested for the optimized FUR ODTs by calculating the Lipschitz value using rats as an animal model. The stability of the ODTs loaded with FUR nanoparticles was assessed under accelerated conditions for 6 months. Finally, the ODT formula loaded with FUR NPs showed a rapid onset of action that was significantly faster than untreated drugs. Nanonization and ODT formulation enhances the dissolution rate and bioavailability of FUR. Many factors can be controlled to achieve optimization results, including the formulation and process parameters.

Qualification of In Vitro Dissolution Absorption System 2 (IDAS2) with Caco-2 and MDCK Cell Monolayers: Dose Sensitivity Study Using BCS Class I and III Drugs.

This study aimed to validate the In vitro Dissolution Absorption System 2 (IDAS2) containing a biological barrier of Caco-2 or Madin-Darby canine kidney (MDCK) cell monolayer through dose sensitivity studies. Metoprolol and propranolol were selected as Biopharmaceutics Classification System (BCS) Class I model drugs, and atenolol as a Class III model drug. The IDAS2 is comprised of a dissolution vessel (500 mL) and two permeation chambers (2 × 8.0 mL) mounted with Caco-2 or MDCK cell monolayer. One or two immediate-release tablet(s) of the model drug were added to the dissolution vessel, and the time profiles of dissolution and permeation were observed. Greater than 85% of metoprolol and propranolol (tested at two dosing concentrations) were dissolved by 15 min, and all drugs were fully dissolved by 30 min. All three drugs were more permeable across Caco-2 cells than MDCK cells with a linear increase in permeation across both cells at both dose concentrations. Thus, the dose sensitivity of the IDAS2 was demonstrated using both cell barriers. These results indicate a successful qualification of IDAS2 for the development/optimization of oral formulations and that MDCK cells can be utilized as a surrogate for Caco-2 cells.

Spectroscopic characterization and pharmacokinetic evaluation of amorphous solid dispersions of glibenclamide for bioavailability enhancement in Wistar rats.

Oral bioavailability of glibenclamide (Glb) was appreciably improved by the formation of an amorphous solid dispersion with Poloxamer-188 (P-188). Poloxamer-188 substantially enhanced the solubility and thereby the dissolution rate of the biopharmaceutics classification system (BCS) class II drug Glb and simultaneously exhibited a better stabilizing effect of the amorphous solid dispersion prepared by the solvent evaporation method. The physical state of the dispersed Glb in the polymeric matrix was characterized by differential scanning calorimetry, X-ray diffraction, scanning electron microscope and Fourier transform infrared studies. In vitro drug release in buffer (pH 7.2) revealed that the amorphous solid dispersion at a Glb-P-188 ratio of 1:6 (SDE4) improved the dissolution of Glb by 90% within 3h. A pharmacokinetic study of the solid dispersion formulation SDE4 in Wistar rats showed that the oral bioavailability of the drug was greatly increased as compared with the market tablet formulation, Daonil®. The formulation SDE4 resulted in an AUC0-24h ~2-fold higher. The SDE4 formulation was found to be stable during the study period of 6 months.

Cellulose- and Saccharide-Based Orally Dispersible Thin Films Transform the Solid States and Dissolution Characteristics of Poorly Soluble Curcumin.

This study aimed at developing and optimizing the orally dispersible thin film (ODTF) containing a plant-derived drug-curcumin (CUR). CUR belongs to a biopharmaceutical classification system (BCS) class IV compound that requires improving its water solubility and tissue permeability preceding formulation. An ODTF was applied to produce a solid dispersion matrix for CUR to resolve such solubility and permeability problems. The film-forming polymers used in the study were cellulose-based (hydroxypropyl methylcellulose/HPMC and carboxymethylcellulose/CMC) and saccharide-based maltodextrin (MDX). Poloxamer (POL) was also employed as surfactant and solubilizer. The solvent casting technique was applied to produce the films. The ethanolic solution of CUR was mixed with an aqueous solution of POLs and then incorporated into different film-forming polymers prior to casting. The processing of the CUR with POL solution was intended to aid in the even dispersion of the drug in the polymeric matrices and enhance the wettability of the films. The physical state and properties of the films were characterized in terms of their morphology, crystallinity of the drug, and phase miscibility of the mixtures. The dissolution profile of the films was also evaluated in terms of dissolution rate and dissolution efficiency. The obtained ODTF products were smooth and flat-surfaced. Physical characterization also indicated that the CUR was homogeneously dispersed in the ODTFs and no longer existed as crystalline material as revealed by X-ray diffraction (XRD). The CUR was also not phase-separated from the films as disclosed by differential scanning calorimetry (DSC). Such dispersion was achieved through the solubilizing effect of POLs and compact polymeric film matrices that prevented the CUR from recrystallization. Furthermore, the ODTFs also improved the dissolution of CUR by 3.2-fold higher than the raw CUR. Overall, cellulose-based films had favorable physical properties compared with saccharide-based films.

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 AUCtotal 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.

Amelioration of tableting properties and dissolution rate of naproxen co-grinded with nicotinamide: preparation and characterization of co-grinded mixture

Objective and significance Reducing the dimensions, when other additives are present, shows potential as a method to improve the dissolution and solubility of biopharmaceutical classification system class II drugs that have poor solubility. In this investigation, the process involved grinding naproxen with nicotinamide with the aim of improving solubility and the rate of dissolution. Methods Naproxen was subjected to co-milling with urea, dimethylurea, and nicotinamide using a planetary ball mill for a duration of 90 min, maintaining a 1:1 molar ratio for the excipients (screening studies). The co-milled combinations, naproxen in its pure milled form, and a physical mixture were subjected to analysis using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), and solubility assessment. The mixture displaying the highest solubility (naproxen-nicotinamide) was chosen for further investigation, involving testing for intrinsic dissolution rate (IDR) and Fourier-transform infrared spectroscopy (FTIR) after co-milling for both 90 and 480 min. Results and conclusion The co-milled combination, denoted as S-3b and consisting of the most substantial ratio of nicotinamide to naproxen at 1:3, subjected to 480 min of milling, exhibited a remarkable 45-fold increase in solubility and a 9-fold increase in IDR. XRPD analysis of the co-milled samples demonstrated no amorphization, while SEM images portrayed the aggregates of naproxen with nicotinamide. FTIR outcomes negate the presence of any chemical interactions between the components. The co-milled sample exhibiting the highest solubility and IDR was used to create a tablet, which was then subjected to comprehensive evaluation for standard attributes. The results revealed improved compressibility and dissolution properties.

Physicochemical Characterization of Hydroxyapatite Hybrids with Meloxicam for Dissolution Rate Improvement.

Organic-inorganic hybrids represent a good solution to improve the solubility and dissolution rates of poorly soluble drugs whose number has been increasing in the last few years. One of the most diffused inorganic matrices is hydroxyapatite (HAP), which is a biocompatible and osteoconductive material. However, the understanding of the hybrids' functioning mechanisms is in many cases limited; thus, thorough physicochemical characterizations are needed. In the present paper, we prepared hybrids of pure and Mg-doped hydroxyapatite with meloxicam, a drug pertaining to the Biopharmaceutical Classification System (BCS) class II, i.e., drugs with low solubility and high permeability. The hybrids' formation was demonstrated by FT-IR, which suggested electrostatic interactions between HAP and drug. The substitution of Mg in the HAP structure mainly produced a structural disorder and a reduction in crystallite sizes. The surface area of HAP increased after Mg doping from 82 to 103 m2g-1 as well as the pore volume, justifying the slightly high drug amount adsorbed by the Mg hybrid. Notwithstanding the low drug loading on the hybrids, the solubility, dissolution profiles and wettability markedly improved with respect to the drug alone, particularly for the Mg doped one, which was probably due to the main distribution of the drug on the HAP surface.

Formulation, Optimization and Evaluation of Solid Dispersion of Deferasirox Using Factorial Design

Deferasirox, an oral iron-chelating agent, is a poorly soluble drug (Biopharmaceutical Classification System class II) having insufficient solubility in physiological fluids resulting in low bioavailability of the drug. The idea behind the present study was to explore the prospects of solid dispersion as a prolific method to enhance the dissolution rate of drug using a water soluble polymer. The solid dispersion was prepared by the solvent evaporation technique using Polyvinyl pyrrolidone with different drug to carrier and solvent ratio. Formulations were characterized through attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), Powder X-ray diffraction (XRD), and in vitro release studies. A 32 factorial design was implemented to obtain optimum solubility, % yield, and optimization of solid dispersion (SD) also quantitates the influence of PVP on the solubility and dissolution profile. Thedrug-to-carrier and solvent ratio was chosen as independent variable, while %yield, drug content, and saturation solubility were chosen as dependent variables. The results showed that the optimized formulation of SD-DFX was able to significantly enhance its solubility. The SD containing a dispersion of Deferasirox with PVP show an exceptional rise in the solubility. This study describes the development of solid dispersion that significantly improved the solubility and bioavailability of DFX. The FTIR studies indicate the interaction between the drug and polymer. The DSC and XRD analysis indicated that the drug was in an amorphous state when dispersed in the polymer. It is resolved that the SD method significantly improves the solubility and dissolution rate, which could also be exploit for other poorly water soluble drug candidates. Keywords: Deferasirox , Polyvinyl pyrrolidone, solid dispersion, Factorial design, Solubility

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 tradeoff between permeability and solubility emerged through the mixed hydrotropic solubilization 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.

New Hydrophilic Matrix Tablets for the Controlled Released of Chlorzoxazone.

The modified release of active substances such as chlorzoxazone from matrix tablets, based on Kollidon®SR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on Kollidon®SR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20-40 w/w % Kollidon®SR, 3-7 w/w % chitosan while the auxiliary substances: Aerosil® 1 w/w %, magnesium stearate 0.5 w/w % and Avicel® up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0-2 h) and the second (2-36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1-the similarity factor, and f2-the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample.

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.