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 - 400 nm 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.

Preparation and Evaluation of Berberine-Excipient Complexes in Enhancing the Dissolution Rate of Berberine Incorporated into Pellet Formulations.

Berberine is used in the treatment of metabolic syndrome and its low solubility and very poor oral bioavailability of berberine was one of the primary hurdles for its market approval. This study aimed to improve the solubility and bioavailability of berberine by preparing pellet formulations containing drug-excipient complex (obtained by solid dispersion). Berberine-excipient solid dispersion complexes were obtained with different ratios by the solvent evaporation method. The maximum saturation solubility test was performed as a key factor for choosing the optimal complex for the drug-excipient. The properties of these complexes were investigated by FTIR, DSC, XRD and dissolution tests. The obtained pellets were evaluated and compared in terms of pelletization efficiency, particle size, mechanical strength, sphericity and drug release profile in simulated media of gastric and intestine. Solid-state analysis showed complex formation between the drug and excipients used in solid dispersion. The optimal berberine-phospholipid complex showed a 2-fold increase and the optimal berberine-gelucire and berberine-citric acid complexes showed more than a 3-fold increase in the solubility of berberine compared to pure berberine powder. The evaluation of pellets from each of the optimal complexes showed that the rate and amount of drug released from all pellet formulations in the simulated gastric medium were significantly lower than in the intestine medium. The results of this study showed that the use of berberine-citric acid or berberine-gelucire complex could be considered a promising technique to increase the saturation solubility and improve the release characteristics of berberine from the pellet formulation.

More Than a Gut Feeling─A Combination of Physiologically Driven Dissolution and Pharmacokinetic Modeling as a Tool for Understanding Human Gastric Motility.

In vivo studies of formulation performance with in vitro and/or in silico simulations are often limited by significant gaps in our knowledge of the interaction between administered dosage forms and the human gastrointestinal tract. This work presents a novel approach for the investigation of gastric motility influence on dosage form performance, by combining biopredictive dissolution tests in an innovative PhysioCell apparatus with mechanistic physiology-based pharmacokinetic modeling. The methodology was based on the pharmacokinetic data from a large (n = 118) cohort of healthy volunteers who ingested a capsule containing a highly soluble and rapidly absorbed drug under fasted conditions. The developed dissolution tests included biorelevant media, varied fluid flows, and mechanical stress events of physiological timing and intensity. The dissolution results were used as inputs for pharmacokinetic modeling that led to the deduction of five patterns of gastric motility and their prevalence in the studied population. As these patterns significantly influenced the observed pharmacokinetic profiles, the proposed methodology is potentially useful to other in vitro-in vivo predictions involving immediate-release oral dosage forms.

Parameterization of Physiologically Based Biopharmaceutics Models: Workshop Summary Report.

This Article shares the proceedings from the August 29th, 2023 (day 1) workshop "Physiologically Based Biopharmaceutics Modeling (PBBM) Best Practices for Drug Product Quality: Regulatory and Industry Perspectives". The focus of the day was on model parametrization; regulatory authorities from Canada, the USA, Sweden, Belgium, and Norway presented their views on PBBM case studies submitted by industry members of the IQ consortium. The presentations shared key questions raised by regulators during the mock exercise, regarding the PBBM input parameters and their justification. These presentations also shed light on the regulatory assessment processes, content, and format requirements for future PBBM regulatory submissions. In addition, the day 1 breakout presentations and discussions gave the opportunity to share best practices around key questions faced by scientists when parametrizing PBBMs. Key questions included measurement and integration of drug substance solubility for crystalline vs amorphous drugs; impact of excipients on apparent drug solubility/supersaturation; modeling of acid-base reactions at the surface of the dissolving drug; choice of dissolution methods according to the formulation and drug properties with a view to predict the in vivo performance; mechanistic modeling of in vitro product dissolution data to predict in vivo dissolution for various patient populations/species; best practices for characterization of drug precipitation from simple or complex formulations and integration of the data in PBBM; incorporation of drug permeability into PBBM for various routes of uptake and prediction of permeability along the GI tract.

Trimethoprim-Based multicomponent solid Systems: Mechanochemical Screening, characterization and antibacterial activity assessment.

In this work, multicomponent trimethoprim-based pharmaceutical solid systems were developed by mechanochemistry, using coformers from the GRAS list and other active pharmaceutical ingredients. The choice of coformers took into account their potential to increase the aqueous solubility/dissolution rate of TMP or its antibacterial activity. All the binary systems were characterized by thermal analysis, powder X-ray diffraction and infrared spectroscopy, and 3 equimolar systems with FTIR pointing to salts, and 4 eutectic mixtures were identified. The intrinsic dissolution rate of TMP in combination with nicotinic acid (a salt) and with paracetamol (eutectic mixture) were 25% and 5% higher than for pure TMP, respectively. For both Gram-positive and -negative strains, the antibacterial activity of TMP with some of the coformers was improved, since the dosage used was lower than the TMP control. A significant increase in antibacterial activity against E. coli was found for the eutectic mixture with curcumin, with the best results being obtained for the eutectic and equimolar mixtures with ciprofloxacin.. Combining trimethoprim with coformers offers an interesting alternative to using trimethoprim alone: multicomponent forms with enhanced TMP dissolution rates were identified, as well as combinations showing enhanced antibacterial activity relatively to the pure drug.

Specific inter-molecular interaction with sodium glycocholate generates the co-amorphous system showing higher physical stability and aqueous solubility of Y5 receptor antagonist of neuropeptide Y, a brick dust molecule.

Drugs with poor water and lipid solubility are termed "brick dust." We previously successfully developed a co-amorphous system of a novel neuropeptide Y5 receptor antagonist (AntiY5R), a brick dust molecule, using sodium taurocholate (NaTC) as a co-former. However, the maximum improvement in AntiY5R dissolution by the co-amorphous system was only approximately 10 times greater than that of the crystals. Therefore, in the current study, other bile salts, including sodium cholate (NaC), sodium chenodeoxycholate (NaCC), and sodium glycocholate (NaGC), were examined as co-formers to further improve AntiY5R dissolution. NaC, NaCC, and NaGC have glass transition temperatures above 150 °C. All three co-amorphous systems prepared successfully retained the amorphous form of AntiY5R for 3 months at 40 °C, but the co-amorphous system with NaGC (AntiY5R-NaGC; 1:9 M ratio) provided the highest improvement in AntiY5R dissolution, which was approximately 50 times greater than that of the crystals. Possible intermolecular interactions via the glycine moiety of NaGC more than the other bile salts would contribute to the highest dissolution enhancement with AntiY5R-NaGC. Thus, NaGC would be a promising co-former for formulating stable co-amorphous systems to enhance the dissolution behavior of brick dust molecules.

A Model of Linear Response with Progressive Decay Equally Suited for RiboGreen® Quantitation of RNA and Dissolution of Solid Oral Dosage Forms.

A new regression model is presented which offers flexibility, freedom from subjective determinations of linear range, and very wide applicability to measurement systems of industrial importance. This "progressive decay" model starts as a deceptively simple ordinary differential equation. We show here that its solution faithfully describes real but seemingly unconnected data from a plate-based assay for quantitation of RNA with RiboGreen® and dissolution data for a triple fixed-dose combination solid oral dosage form.

Preparation, optimization, and characterization of genistein-ginseng long-acting polymeric gel as a breast cancer treatment alternative.

To address the prevalent genistein (GST) metabolism and inadequate intestinal absorption, an oral long-acting and gastric in-situ gelling gel was designed to encapsulate and localize the intestinal release of the loaded genistein-ginseng (GST-GNS) solid dispersion. Because of the high breast perfusion of GST upon oral absorption, the GST-GNS solid dispersion was developed to enhance GST's dissolution and penetration while offering a synergistic impact against breast cancer (BC). Physiochemical analysis of the GST-GNS solid dispersion, release analysis, gel characterizations, storage stability, penetration, and in vitro cytotoxicity studies were carried out. GST-GNS solid dispersion showed improved dissolution and penetration as compared to raw GST. GST-GNS solid dispersion homogenous shape particles and hydrophilic contacts were revealed by scanning electron microscopy and Fourier Transform-Infrared analysis, respectively. GST-GNS solid dispersion's diffractogram shows the amorphous character. A second modification involved creating a gastric in-situ gelling system loaded with GST-GNS solid dispersion. This system demonstrated improved GST penetration employing the solid dispersion, as well as the localizing of the GST release at the intestinal media and antitumor synergism against BC. For a better therapeutic approach for BC, the innovative oral GST long-acting gel encasing the GST-GNS solid dispersion would be recommended.

Quantification of Soluplus for Dissolution Tests: SEC Method Development and Validation.

The quantification of both polymer and drug during the dissolution of an amorphous solid dispersion (ASD) in aqueous media arouses great interest and may aid in the formulation. However, the available quantification methods for polymer excipients are limited, expensive, and challenging compared to drugs. In this work, a size exclusion chromatography method (HPLC-SEC) was developed and validated to determine the concentration of a frequently used polymer excipient, Soluplus® (Sol). In order to develop a method for the quantification of dissolved Soluplus®, two methods (SEC-UV and SEC-RID) with two injection volumes were tested with standard solutions of three different batches of Soluplus. The developed HPLC-SEC-UV method showed acceptable linearity (R2 > 0.9990) for all batches of Soluplus, good accuracies above a concentration of 0.1 mg/mL (coefficient of variation < 2%), relatively good precision at a concentration of 0.1 mg/mL (coefficient of variation < 2.5%), and high recoveries at a concentration of 0.75 mg/mL (coefficient of variation < 0.5%). The presence of Felodipine (Fel) and Lumefantrine (Lum) in the liquid media did not interfere with Soluplus quantification. The use of various surfactants, such as Tween® 80, Tween® 20, Span® 80, Span® 20, Kolliphor® TPGS, and sodium lauryl sulphate at a low concentration (0.005 mg/mL) did not show any effect on Soluplus® and did not interfere with Soluplus® quantification with any of the Soluplus batches. The addition of lithium bromide (LiBr) to the mobile phase within a concentration range of 0.05 to 1.0 M did not improve Soluplus® quantification.

Long-Term Physical Stability of Amorphous Solid Dispersions: Comparison of Detection Powers of Common Evaluation Methods for Spray-Dried and Hot-Melt Extruded Formulations.

Although physical stability can be a critical issue during the development of amorphous solid dispersions (ASDs), there are no established protocols to predict/detect their physical stability. In this study, we have prepared fenofibrate ASDs using two representative manufacturing methods, hot-melt extrusion and spray-drying, to investigate their physical stability for one year. Intentionally unstable ASDs were designed to compare the detection power of each evaluation method, including X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and dissolution study. Each method did not provide the same judgment results on physical stability in some cases because of their different evaluation principles and sensitivity, which has been well-comprehended only for one-component glass. This study revealed that the detection powers of each evaluation method significantly depended on the manufacturing methods. DSC was an effective method to detect a small amount of crystals for both types of ASDs in a quantitative manner. Although the sensitivity of XRPD was always lower compared to that of DSC, interpretation of the data was the easiest. SEM was very effective for observing the crystallization of the small amount of drug for hot-melt extruded products, as the drug crystal vividly appeared on the large grains. The dissolution performance of spray-dried products could change even without any indication of physical change including crystallization. The advantage/disadvantage and complemental roles of each evaluation method are discussed for deeper understanding on the physical stability data of ASDs.

Controlled dissolution of physically cross-linked locust bean gum - κ-carrageenan hydrogels.

Most hydrogels swell but do not dissolve in water since their chains are tied to each other. Nevertheless, some hydrogels disintegrate under physiological conditions, a property that could be beneficial in emerging applications, including sacrificial materials, 3D bioprinting, and wound dressings. This paper proposes a novel approach to control the dissolution rate of hydrogels based on the integration of kappa carrageenan nanoparticles (KCAR-NPs) into kappa carrageenan (KCAR) and locust bean gum (LBG) hydrogels to obtain a three-component hybrid system. KCAR and LBG are known to have synergistic interactions, where physical interactions and chain entanglements lead to their gelation. We hypothesized that integrating the bulky nanoparticles would disturb the three-dimensional network formed by the polysaccharide chains and enable manipulating the dissolution rate. Compression, water absorption, rheology, and cryo-scanning electron microscopy measurements were performed to characterize the physical properties and structure of the hydrogels. The hybrid hydrogels displayed much faster dissolution rates than a control system without nanoparticles, which did not completely dissolve within 50 days and offered a cutting-edge means to finely adjust hydrogel dissolution through modulation of KCAR and KCAR-NPs concentrations. The new hydrogels also exhibited shear-thinning and self-healing properties resulting from the weak and reversible nature of the physical bonds.

Construction of chitosan/alginate aerogels with three-dimensional hierarchical pore network structure via hydrogen bonding dissolution and covalent crosslinking synergistic strategy for thermal management systems.

To replace traditional petrochemical-based thermal insulation materials, in this work, the chitosan (CHI)/alginate (ALG) (CA) aerogels with three-dimensional hierarchical pore network structure were constructed by compositing CHI and ALG using a synergistic strategy of hydrogen bonding dissolution and covalent crosslinking. The structure and properties were further regulated by crosslinking the CA aerogels with epichlorohydrin (ECH). The CA aerogels exhibited various forms of covalent crosslinking, hydrogen bonding and electrostatic interactions, with hydrogen bonding content reaching 79.12 %. The CA aerogels showed an excellent three-dimensional hierarchical pore network structure, with an average pore size minimum of 15.92 nm. The structure regulation of CA aerogels obtained excellent compressive properties, with an increase of stress and strain by 137.61 % and 45.05 %, which can support a heavy object 5000 times its weight. Additionally, CA aerogels demonstrate excellent thermal insulation properties and low thermal conductivity, comparable to commercially available insulation materials. More importantly, CA aerogels have good cyclic insulation stability and thermal properties, and they have a flame retardancy rating of V-0, which shows the stability of insulation properties and excellent safety. CA aerogels provide new ideas for the development of biomass thermal insulation materials and are expected to be candidates for thermal management applications.

Generality of Enhancing the Dissolution Rates of Free Acid Amorphous Solid Dispersions by the Incorporation of Sodium Hydroxide.

The incorporation of a counterion into an amorphous solid dispersion (ASD) has been proven to be an attractive strategy to improve the drug dissolution rate. In this work, the generality of enhancing the dissolution rates of free acid ASDs by incorporating sodium hydroxide (NaOH) was studied by surface-area-normalized dissolution. A set of diverse drug molecules, two common polymer carriers (copovidone or PVPVA and hydroxypropyl methylcellulose acetate succinate or HPMCAS), and two sample preparation methods (rotary evaporation and spray drying) were investigated. When PVPVA was used as the polymer carrier for the drugs in this study, enhancements of dissolution rates from 7 to 78 times were observed by the incorporation of NaOH into the ASDs at a 1:1 molar ratio with respect to the drug. The drugs having lower amorphous solubilities showed greater enhancement ratios, providing a promising path to improve the drug release performance from their ASDs. Samples generated by rotary evaporation and spray drying demonstrated comparable dissolution rates and enhancements when NaOH was added, establishing a theoretical foundation to bridge the ASD dissolution performance for samples prepared by different solvent-removal processes. In the comparison of polymer carriers, when HPMCAS was applied in the selected system (indomethacin ASD), a dissolution rate enhancement of 2.7 times by the incorporated NaOH was observed, significantly lower than the enhancement of 53 times from the PVPVA-based ASD. This was attributed to the combination of a lower dissolution rate of HPMCAS and the competition for NaOH between IMC and HPMCAS. By studying the generality of enhancing ASD dissolution rates by the incorporation of counterions, this study provides valuable insights into further improving drug release from ASD formulations of poorly water-soluble drugs.

Computer-driven formulation development of Ginsenoside Rh2 ternary solid dispersion.

(20 S)-Ginsenoside Rh2 is a natural saponin derived from Panax ginseng Meyer (P. ginseng), which showed significantly potent anticancer properties. However, its low water solubility and bioavailability strongly restrict its pharmaceutical applications. The aim of current research is to develop a modified (20 S)-Ginsenoside Rh2 formulation with high solubility, dissolution rate and bioavailability by combined computational and experimental methodology. The "PharmSD" model was employed to predict the optimal polymer for (20 S)-Ginsenoside Rh2 solid dispersion formulations. The solubility of (20 S)-Ginsenoside Rh2 in various polymers was assessed, and the optimal ternary solid dispersion was evaluated across different dissolution mediums. Characterization techniques included the Powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR). Molecular dynamics simulations were employed to elucidate the formation mechanism of the solid dispersion and the interactions among active pharmaceutical ingredient (API) and excipient molecules. Cell and animal experiments were conducted to evaluate the in vivo performance of the modified formulation. The "PharmSD" solid dispersion model identified Gelucire 44/14 as the most effective polymer for enhancing the dissolution rate of Rh2. Subsequent experiment also confirmed that Gelucire 44/14 outperformed the other selected polymers. Moreover, the addition of the third component, sodium dodecyl sulfate (SDS), in the ternary solid dispersion formulation significantly amplified dissolution rates than the binary systems. Characterization experiments revealed that the API existed in an amorphous state and interacted via hydrogen bonding with SDS and Gelucire. Moreover, molecular modeling results provided additional evidence of hydrogen bonding interactions between the API and excipient molecules within the optimal ternary solid dispersion. Cell experiments demonstrated efflux ratio (EfR) of Rh2 ternary solid dispersion was lower than that of pure Rh2. In vivo experiments revealed that the modified formulation substantially improved the absorption of Rh2 in rats. Our research successfully developed an optimal ternary solid dispersion for Rh2 with high solubility, dissolution rate and bioavailability by integrated computational and experimental tools. The combination of Artificial Intelligence (AI) technology and molecular dynamics simulation is a wise way to support the future formulation development.

Revisiting various mechanistic approaches for cellulose dissolution in different solvent systems: A comprehensive review.

The process of dissolving cellulose is a pivotal step in transforming it into functional, value-added materials, necessitating a thorough comprehension of the underlying mechanisms to refine its advanced processing. This article reviews cellulose dissolution using various solvent systems, along with an in-depth exploration of the associated dissolution mechanisms. The efficacy of different solvents, including aqueous solvents, organic solvents, ionic liquids, hybrid ionic liquid/cosolvent systems, and deep eutectic solvents, in dissolving cellulose is scrutinized, and their limitations and advantages are highlighted. In addition, this review methodically outlines the mechanisms at play within these various solvent systems and the factors influencing cellulose solubility. Conclusions drawn highlight the integral roles of the degree of polymerization, crystallinity, particle size, the type and sizes of cations and anions, alkyl chain length, ionic liquid/cosolvent ratio, viscosity, solvent acidity, basicity, and hydrophobic interactions in the dissolution process. This comprehensive review aims to provide valuable insights for researchers investigating biopolymer dissolution in a broader context, thereby paving the way for broader applications and innovations of these solvent systems.

Predictable patterns within the kelp forest can indirectly create temporary refugia from ocean acidification.

Kelps are recognized for providing many ecosystem services in coastal areas and considered in ocean acidification (OA) mitigation. However, assessing OA modification requires an understanding of the multiple parameters involved in carbonate chemistry, especially in highly dynamic systems. We studied the effects of sugar kelp (Saccharina latissima) on an experimental farm at the north end of Hood Canal, Washington-a low retentive coastal system. In this field mesocosm study, two oyster species (Magallana gigas, Ostrea lurida) were exposed at locations in the mid, edge, and outside the kelp array. The Hood Head Sugar Kelp Farm Model outputs were used to identify dominating factors in spatial and temporal kelp dynamics, while wavelet spectrum analyses helped in understanding predictability patterns. This was linked to the measured biological responses (dissolution, growth, isotopes) of the exposed organisms. Positioned in an area of high (sub)-diel tidal fluxes with low retention potential, there were no measurable alterations of the seawater pH at the study site, demonstrating that the kelp array could not induce a direct mitigating effect against OA. However, beneficial responses in calcifiers were still observed, which are linked to two causes: increased pH predictability and improved provisioning through kelp-derived particulate organic resource utilization and as such, kelp improved habitat suitability and indirectly created refugia against OA. This study can serve as an analogue for many coastal bay habitats where prevailing physical forcing drives chemical changes. Future macrophyte studies that investigate OA mitigating effects should focus also on the importance of predictability patterns, which can additionally improve the conditions for marine calcifiers and ecosystem services vulnerable to or compromised by OA, including aquaculture sustainability.

Real-time release testing of in vitro dissolution and blend uniformity in a continuous powder blending process by NIR spectroscopy and machine vision.

Continuous manufacturing is gaining increasing interest in the pharmaceutical industry, also requiring real-time and non-destructive quality monitoring. Multiple studies have already addressed the possibility of surrogate in vitro dissolution testing, but the utilization has rarely been demonstrated in real-time. Therefore, in this work, the in-line applicability of an artificial intelligence-based dissolution surrogate model is developed the first time. NIR spectroscopy-based partial least squares regression and artificial neural networks were developed and tested in-line and at-line to assess the blend uniformity and dissolution of encapsulated acetylsalicylic acid (ASA) - microcrystalline cellulose (MCC) powder blends in a continuous blending process. The studied blend is related to a previously published end-to-end manufacturing line, where the varying size of the ASA crystals obtained from a continuous crystallization significantly affected the dissolution of the final product. The in-line monitoring was suitable for detecting the variations in the ASA content and dissolution caused by the feeding of ASA with different particle sizes, and the at-line predictions agreed well with the measured validation dissolution curves (f2 = 80.5). The results were further validated using machine vision-based particle size analysis. Consequently, this work could contribute to the advancement of RTRT in continuous end-to-end processes.

Fabrication and characterization of cocoa butter-based caffeine fast-melting tablets.

Aim: The objective of this study was to develop and characterize the physical properties of fast-melting tablets (FMTs) using cocoa butter as the base and caffeine as the model drug. Method: The simple refrigerator freezing method was employed to prepare caffeine-loaded, FMTs from cocoa butter bases. Results: The F3 chosen formulation achieved a disintegration time of 1.20 min ± 0.035, which falls within the specified limit set by the European Pharmacopoeia. The cumulative drug release data of F3, was 88.52 and 94.08% within 60 and 75 min, respectively (NLT 85% as per US FDA requirement). All the other physical test standards for FMTs met the pharmacopeial specifications. Conclusion: Based on the findings, the simple refrigerator freezing method could be used to formulate FMTs.

Patient-friendly natural caffeine-loaded cocoa butter-based fast-melting tablets with rapid disintegration, affordability, safety and biocompatibility are an efficient base for drug delivery.

Assessing the efficacy of various irrigation solutions in dissolving organic tissue.

For successful root canal treatment, adequate chemomechanical instrumentation to eliminate microorganisms and pulp tissue is crucial. This study aims to assess the organic tissue dissolving activity of various irrigation solutions on bovine tooth pulp tissue. 40 extracted bovine mandibular anterior teeth (n = 10) were used for the study. Bovine pulp pieces (25 ± 5 mg) were placed in 1.5 ml Eppendorf tubes. Each tooth pulp sample was then covered with 1.5 ml of different irrigation solutions, dividing them into four groups: Group 1 with freshly prepared 5% Boric acid, Group 2 with 5% NaOCl, Group 3 with Irritrol, and Group 4 with Saline. Samples were left at room temperature for 30 min, then dried and reweighed. The efficacy of tissue dissolution ranked from highest to lowest was found to be NaOCl, Boric Acid, Irritrol, and saline (p < 0.05). It was observed that the decrease in the NaOCl group was greater than the decrease in the Irritrol and saline groups, and the decrease in the Boric acid group was significantly greater than the decrease in the saline group (p < 0.05). It also emphasizes the need for future studies to further investigate the effects of Irritrol and Boric Acid on tissue dissolution.

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.