Dissolution Studies Research Articles

Development of Polyvinyl Alcohol/Polyethylene Glycol Copolymer-based Orodispersible Films Loaded with Entecavir: Formulation and In vitro Characterization.

The aim of the study is to prepare entecavir (ETV)-loaded orodispersible films (ODFs) using polyvinyl alcohol (PVA)/polyethylene glycol (PEG) graft copolymer (Kollicoat® IR) as a film-forming agent, and further to evaluate the dissolution rate, mechanical and physicochemical properties of films. ETV-ODFs were prepared by a solvent casting method. The amount of film-forming agent, plasticizer, and disintegrating agent was optimized in terms of the appearance, thickness, disintegration time and mechanical properties of ODFs. The compatibility between the drug and each excipient was conducted under high temperature (60 °C), high humidity (RH 92.5%), and strong light (4500 Lx) for 10 days. The dissolution study of optimal ODFs compared with the original commercial tablet (Baraclude®) was performed using a paddle method in pH 1.0, pH 4.5, pH 6.8, and pH 7.4 media at 37 °C. The morphology of ODFs was observed via scanning electron microscopy (SEM). The mechanical properties such as tensile strength (TS), elastic modulus (EM), and percentage elongation (E%) of ODFs were evaluated using the universal testing machine. The physicochemical properties of ODFs were investigated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). The related substances were less than 0.5% under high temperature, high humidity, and strong light for 10 days when ETV was mixed with excipients. The optimal formulation of ODFs was set as the quality ratio of Kollicoat® IR, glycerol, sodium alginate (ALG-Na): TiO2: MCC+CMC-Na: ETV was 60:9:12:1:1:1. The drug-loaded ODFs were white and translucent with excellent stripping property. The thickness, disintegration time, EM, TS, and E% were 103.33±7.02 μm, 25.31±1.95 s, 25.34±8.69 Mpa, 2.14±0.26 Mpa, and 65.45±19.41 %, respectively. The cumulative drug release from ODFs was more than 90% in four different media at 10 min. The SEM showed that the drug was highly dispersible in ODFs, and the XRD, DSC, and FT-IR results showed that there occurred some interactions between the drug and excipients. In conclusion, the developed ETV-loaded ODFs showed relatively short disintegration time, rapid drug dissolution, and excellent mechanical properties. This might be an alternative to conventional ETV Tablets for the treatment of chronic hepatitis B.

Valsartan/2-Aminopyridine Co-Amorphous System: Preparation, Characterization, and Supramolecular Structure Simulation by Density Functional Theory Calculation.

The objective of this work was to improve the solubility and discover a stable co-amorphous form of valsartan (VAL), a BCS class-II drug, by utilizing small molecule 2-Aminopyridine (2-AP) in varying molar ratios (2:1, 1:1, and 1:2), employing a solvent evaporation technique. Additionally, by way of a density functional theory (DFT)-based computational method with commercially available software, a new approach for determining the intermolecular connectivity of multi-molecular hydrogen bonding systems was proposed. The binary systems' features were characterized by PXRD, DSC, FTIR, and Raman spectroscopy, while the equilibrium solubility and dissolution was determined in 0.1 N HCL and water conditions to investigate the dissolution advantage of the prepared co-amorphous systems. The results demonstrated that the co-amorphous system was successfully prepared in VAL/2-AP with a 1:2 molar ratio following solvent evaporation, whereby the hydrogen bonding sites of VAL were fully occupied. Physical stability studies were carried out under dry conditions at room temperature for 6 months. Furthermore, four possible ternary systems were constructed, and their vibrational modes were simulated by DFT calculations. The calculated infrared spectra of the four configurations varied widely, with trimer 1 showing the most resemblance to the experimental spectrum of the co-amorphous 1:2 system. Additionally, co-amorphous VAL/2-AP displayed significant improvement in the solubility and dissolution study. Notably, in the 1:2 ratio, there was almost a 4.5-fold and 15.6-fold increase in VAL's solubility in 0.1 N HCL and water environments, respectively. In conclusion, our findings highlight the potential of co-amorphous systems as a feasible approach to improving the properties and bioavailabilities of insoluble drugs. The proposed simulation method provides valuable insights into determining the supramolecular structure of multi-molecular hydrogen bonding systems, offering a novel perspective for investigating such systems.

Three Strikingly Different Crystal Habits of Tadalafil: Design, Characterization, Pharmaceutical Performance, and Computational Studies.

The present study aims at improving the physicochemical properties of a widely used drug Tadalafil through crystal habit modification, without changing the polymorphic form. Three distinct types of crystal habits, namely, needle, plate, and block, were obtained under controlled crystallization protocols with optimized solvent compositions. Complete characterization of these three crystal habits was carried out using powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and Fourier transform infrared spectroscopy. Morphological features were studied by optical and scanning electron microscopy. Evaluation of the pharmaceutical performance of different crystal habits reveals significant improvement in compressibility and flow properties for the block-shaped crystals in comparison to the needle- and plate-shaped crystals. Also, a more linear tablet compression behavior was noted for the plate and block morphologies of the API compared to their needle counterpart. In vitro dissolution studies showed distinct release profiles for the same API form with different crystal habits, i.e., needle > plate > block. Insights into crystal growth mechanism and the role of solvents in affording the observed crystal habits are presented based on molecular dynamics simulations of intermolecular interactions with crystal facets, in conjunction with the experimental crystal face indexing of the single crystals of different habits. These observations were further supported by interaction topology analysis and the electrostatic features on different crystal facets.

Development and characterization of a self-nano emulsifying drug delivery system (SNEDDS) for Ornidazole to improve solubility and oral bioavailability of BCS class II drugs

This study aimed to investigate the in vitro performance of self-nanoemulsifying drug delivery systems (SNEDDSs) of Ornidazole (ORD), a poorly water-soluble drug. Self-nanoemulsifying drug delivery systems of ORD were prepared using various oils, non-ionic surfactants, and/or water-soluble co-solvents and assessed visually/by droplet size measurement. Equilibrium solubility of ORD in the anhydrous and diluted SNEDDS was conducted to achieve the maximum drug loading. The in vitro dissolution of SNEDDS was studied to compare the solubility of the representative formulations with API. The results from the characterization and solubility studies showed that SNEDDS formulations were stable with lower droplet sizes and showed higher ORD solubility. From the dissolution studies, it was found that the developed A7-SNEDDS formulation provided a significantly higher rate of ORD release (98.94 ± 0.68 in 1.0 h) compared to API. ORD-loaded SNEDDS formulations could be a potential oral pharmaceutical product with high drug-loading capacity, improved drug dissolution, and enhanced oral bioavailability.

Pharmaceutical Equivalence of Film-Coated and Chewable Tablets: A Comparative Dissolution Study Using Pulverized Chewable Tablets.

Famotidine is a histamine H2 receptor antagonist used in the treatment of gastrointestinal disorders. It is available in multiple formulations, including film-coated tablets, chewable tablets, oral suspension, and injections. The purpose of this study was to develop and evaluate the film-coated tablet (FT) containing famotidine, magnesium hydroxide, and precipitated calcium carbonate, designed to be pharmaceutically equivalent to the marketed chewable tablet (CT). To achieve the pharmaceutical equivalence of two tablets, the dissolution profiles of FT should be similar to those of CT. However, since CT is intended to be chewed before swallowing, testing it in its intact form would not provide accurate results. Therefore, pulverized chewable tablets (PCT) were used as the reference product. The dissolution, performed by the paddle method at 50 rpm, was analyzed by the validated UV method. Similarity factor (f2) and difference factor (f1) were calculated to assess the equivalence of the dissolution profiles. The results demonstrated that the dissolution profiles of the FT and CT were similar. Additionally, the acid-neutralizing capacity test confirmed the equivalence of the two antacids. This study is one of the first to propose that dissolution tests for pharmaceutical equivalence should be conducted on pulverized CTs when developing generic equivalents to CTs.

Novel Pharmaceutical Cocrystal Consisting of Chlorzoxazone and Nicotinamide: A New Promising Carrier for Solubility Augmentation.

Chlorzoxazone (CHZ) is a centrally acting muscle relaxant used to treat muscle spasms. It is employed as a first-line medication for treating muscle spasms, offering both musculoskeletal relaxation and mild sedative effects. According to the biopharmaceutics classification system, it belongs to class II drug having poor solubility and high permeability. In order to improve the flow property, water solubility, and dissolution of CHZ, CHZ-nicotinamide (NA) cocrystal was prepared by liquid-assisted grinding cocrystallization (LAG CC) method using methanol as the choice of solvent. CHZ-NA cocrystal was characterized by differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectrometry, and scanning electron microscopy (SEM). DSC scan showed a sharp endothermic peak shift, which is caused by the formation of a new crystal form with altered physical properties, which was further confirmed by PXRD. Also, a change in the surface morphology of LAG CC compared to CHZ was observed in SEM. The resultant CHZ-NA cocrystal displayed improved powder flow properties compared to the native form of CHZ. LAG CC demonstrated a 3.1- and 2.6-fold increase in saturated solubility and intrinsic dissolution rate, respectively, compared to CHZ alone. Furthermore, the in vitro dissolution study showed that the cumulative dissolution of CHZ in 2 h was about 53%. Whereas, dissolution of LAG CC reached 99% in 2 h, showing obvious dissolution improvement. Thus, CHZ-NA cocrystal could significantly improve the flow properties, solubility and dissolution of CHZ.

Formulation and Evaluation of Colon Specific Meloxicam Microcapsules for the Treatment of Arthritis

Objective: The main objective of the current study was to formulate and evaluate meloxicam-loaded microcapsules for colon-specific drug delivery using pH-dependent polymers. The emerging need for developing sustained release NSAIDs to minimize the dosing frequency was the main concern. Consequently, creating an oral sustained release formulation for the treatment of arthritis may be one method to get around this. Methods: Eudragit RS/RL-100 polymers were used in emulsion solvent evaporation processes to create Meloxicam (MLX) microcapsules. Compatibility tests (FTIR), surface morphology by Scanning Electron Microscopy (SEM), yield, drug content, entrapment efficiency, and in vitro dissolution studies were performed on the produced MLX microcapsules. Results: There was no interaction between the polymer and MLX, according to the IR spectra. The microcapsules were spherical in nature, which was confirmed by SEM. Normal frequency distribution MLX microcapsules were produced. The maximum drug entrapment efficiency of 94% was attained. The in vitro performance of MLX microcapsules demonstrated that the polymer concentration influenced sustained release. Furthermore, it was observed that the amount of polymer utilized regulated the release of the drug. Conclusion: Based on the findings, it was concluded that one of the most promising formulation methods for creating colon specific drug delivery systems for the treatment of arthritis is the production of MLX microcapsules.

DEVELOPMENT AND EVALUATION OF CYCLODEXTRIN NANOSPONGES-BASED TOPICAL FORMULATION OF TAZAROTENE

Objective: Tazarotene is used as a topical retinoid for the treatment of acne, psoriasis and sun-damaged skin. But its topical formulation has many side effects, including itching, burning, dryness, redness, stinging, rash blistering, skin discoloration, peeling at the site of application and low bioavailability. The present study focuses on the reduction of side effects and enhancement of solubility and topical bioavailability of tazarotene by using cyclodextrin-based nanosponges. Methods: Nanosponge of tazarotene were prepared by lyophilization method. The physiochemical characterization of plain nanosponges and drug-loaded nanosponges were performed using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and X-ray Diffractometer (XRD) studies. The drug-loaded nanosponges were incorporated into a carpool-based gel formulation. The prepared formulation was evaluated for viscosity, dissolution and stability. FTIR, DSC and XRD studies confirmed the formation of inclusion complex of tazarotene with nanosponges. Results: The particle size of the drug-loaded nanosponges was found to be in the range of 156.72 to 163.48 nm. Transmission Electron Microscopy (TEM) images revealed the regular spherical shape of both the nanosponges that are unaffected even after drug encapsulation. The pH of the gel formulations was found to be in the range of 5.86 to 6.46. The gel formulation resulted in the diffusion of drug in controlled manner for up to 24 h. The in vitro dissolution studies revealed that nanosponges-based topical formulation had better results than the marketed product. Conclusion: Thus, the study showed that nanosponge-based gel formulation can be a possible alternative to conventional formulations of tazarotene with enhanced bioavailability and skin retention characteristics for topical application.

Comparative Dissolution Study of Ciprofloxacin Hydrochloride-sustained Release Tablets by Using Carbopol-934 and Guar Gum Polymers

Aims: This study aimed to identify the potential release of the drug from the tablet dosage form using Carbopol-934 and Guar Gum polymers at different concentration ratios. Objective: The objective of this study was to determine the cumulative percentage of ciprofloxacin hydrochloride released from different polymers. Method: We formulated ciprofloxacin hydrochloride sustained-release tablets with Carbopol-934 and Guar gum using the wet granulation method. For the formulation of sustained-release ciprofloxacin hydrochloride tablets, both polymers were mixed in varying ratios. The tablets were examined for pre-formulation studies, including the angle of repose, bulk density, compressibility index, and physiological properties, such as variations in weight, friability, and drug content. For postformulation studies, such as the in vitro study, the in vitro release of the drugs was evaluated in a phosphate buffer solution (pH 7.4) for 8 h. However, the physiological properties of ciprofloxacin hydrochloride tablets were limited due to their liberality. Results: The tablets containing guar gum (Batches B-I and B-II) showed better drug content than other polymer-based batches, such as Carbopol-934 (Batch A-I, A-II) and a mixture of both polymer Carbopol-934 and Guar gum (Batch C-I, C-II). Sustained drug release was observed in the guar gum polymer-based tablets (Batch B-II). It was observed that the dissolution profile of ciprofloxacin hydrochloride tablets formed using different polymers showed an increase in the polymer ratio, which can be related to the increase in drug release. Conclusion: From this study, we can conclude that the ciprofloxacin hydrochloride drug release percentage was maximum when guar gum polymer was used in the tablet dosage form.

Assessment of the bioactivities of spray-dried pure and Zn-containing bioactive glass by experimental and DFT analysis

The bioactive glass contains CaO, SiO2, and P2O5 in proportion and is applied in bone tissue engineering, plastic surgery, and dentistry because of its excellent bioactivity, biocompatibility, and osteoconductivity. Doping metal ions into a bioactive glass is an efficient way to enhance its functionality and medical applicability. Zn ions have been proven to have a high inhibitory effect on bacterial growth, so Zn-containing bioactive glass has attracted much attention. The literature presents conflicting findings on whether Zn dopants enhance or deteriorate the bioactivity of bioactive glass, and there is no clear answer. To clarify the role of Zn ions on the bioactivity of bioactive glass, pure and Zn-containing bioactive glass samples were synthesized using a spray drying technique followed by in vitro immersion. XPS and theoretical calculations showed that Zn dopants decreased non-bridging oxygen concentration in bioglass. XRD, SEM, and FTIR demonstrated that the Zn dopants decreased bioglass activity. The dissolution study indicated that Zn dopants strongly bond to the non-bridging oxygen near the Ca ion in bioglass, decreasing its bioactivity.

Strap-on Buoyant Device to Enhance Gastrointestinal Tract Retention of Felodipine Osmotic Pump Tablets.

Osmotic pump systems require prolonged retention time in the stomach to provide enhanced bioavailability and regulated release, which is quite challenging. This study used a three-dimensional printing (3DP) technique combined with a gastro-retentive floating device (GRFD) to extend the retention of the osmotic pump in the stomach and enhance its bioavailability. The strap-on buoyant device was fabricated by stereolithography 3DP and incorporated a felodipine osmotic pump tablet used in clinical practice, which enabled it to float in the stomach or dissolution media without any floating lag time. The components of the device were affixed using a snap-fix mechanism. GRFD dissolution study revealed a notable in vitro floating capability, lasting over 24h, with a release profile similarity factor f2 = 65.28 compared to the naked tablet dissolution profile. The pharmacokinetics of felodipine osmotic pump in beagles showed a Cmax of 1.893 ng/mL, which increased to 4.511 ng/mL with GRFD. The delivery of an osmotic pump with GRFD enhanced the AUC0-∞ of felodipine from 10.20 ng/mL·h to 26.54 ng/mL·h. In conclusion, the strap-on buoyant device has been successfully designed to enhance gastrointestinal tract retention of felodipine osmotic pumps and bioavailability in beagles.

Evaluating Various Lactose Types as Solid Carriers for Improving Curcumin Solubility in Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDSs) for Oral Administration

Curcumin, a bioactive compound derived from turmeric, possesses numerous pharmaceutical properties; however, its poor aqueous solubility and permeability result in low bioavailability. This study aims to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) using different lactose types as solid carriers for the oral administration of curcumin to enhance its solubility. The system comprised curcumin, an oil phase, and a surfactant. Jasmine oil, as the oil phase, and Cremophor® RH40, as the surfactant, were selected due to their superior ability to solubilize curcumin. A microemulsion was then prepared using a ternary phase diagram. The liquid SNEDDSs were converted into S-SNEDDSs by employing three solid carriers: Tablettose® 80, FlowLac® 100, and GranuLac® 200. Dissolution studies conducted in simulated gastric fluid demonstrated a significant improvement in curcumin solubility in the S-SNEDDS formulations compared to curcumin powder. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses confirmed the appearance of curcumin in the S-SNEDDS, while Fourier-transform infrared (FTIR) spectroscopy indicated compatibility between the excipients and curcumin. Additionally, an accelerated stability study conducted over four weeks at 40 °C and 75% relative humidity showed no significant changes in the physical appearance of the S-SNEDDS formulations. These findings suggest that the S-SNEDDS formulation effectively enhances curcumin’s solubility, potentially improving its bioavailability for oral administration.

Optimization of Glibenclamide Loaded Thermoresponsive SNEDDS Using Design of Experiment Approach: Paving the Way to Enhance Pharmaceutical Applicability.

Thermoresponsive self-nanoemulsifying drug delivery systems (T-SNEDDS) offer a promising solution to the limitations of conventional SNEDDS formulations. Liquid SNEDDS are expected to enhance drug solubility; however, they are susceptible to leakage during storage. Even though solid SNEDDS offers a solution to this storage instability, they introduce new challenges, namely increased total dosage and potential for drug trapping within the formulation. The invented T-SNEDDS was used to overcome these limitations and improve the dissolution of glibenclamide (GBC). Solubility and transmittance studies were performed to select a suitable oil and surfactant. Design of Experiments (DoE) software was used to study the impact of propylene glycol and Poloxamer 188 concentrations on measured responses (liquefying temperature, liquefying time, and GBC solubility). The optimized formulation was subjected to an in vitro dissolution study. The optimized T-SNEDDS consisted of Kolliphor EL and Imwitor 308 as surfactants and oil. The optimized propylene glycol and Poloxamer 188 concentrations were 13.7 and 7.9% w/w, respectively. It exhibited a liquefying temperature of 35.0 °C, a liquefying time of 119 s, and a GBC solubility of 5.51 mg/g. In vitro dissolution study showed that optimized T-SNEDDS exhibited 98.8% dissolution efficiency compared with 2.5% for raw drugs. This study presents a promising approach to enhance pharmaceutical applicability by resolving the limitations of traditional SNEDDS.

Extrusion-Based Three-Dimensional Printing of Metronidazole Immediate Release Tablets: Impact of Processing Parameters and in Vitro Evaluation

PurposeThe current study assessed the potential of a pneumatic 3D printer in developing a taste-masked tablet in a single step. Metronidazole (MTZ) was chosen as the model drug, and Eudragit® E PO was used as a taste-masking polymer to produce taste-masked tablets.MethodsThe study focused on optimizing processing parameters, such as the nozzle's printing speed, the printhead's heating temperature, and the pressure. Oval-shaped tablets were printed with a rectilinear printing pattern of 30% and 100% infill and evaluated for in vitro drug release and taste masking. The 3D-printed tablets are also characterized using Differential Scanning Calorimetry (DSC), Fourier-transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM).ResultsThe infill density impacts the drug release profile of the tablets. F9, F10, and F11 displayed desired printability among the formulations, with F9 and F10 exhibiting over 85% drug release within 60 min in the in vitro dissolution study. The F9 formulation, with 30% infill, effectively masked the bitter taste of MTZ in the in vitro dissolution study carried out in a pH 6.8 artificial salivary medium. The observed release was below the tasting threshold concentration of the model drug.ConclusionIn summary, 3-dimensional extrusion-based printing combines the effects of hot-melt extrusion and fused deposition modeling techniques in a single-step process, demonstrating potential as an alternative to the fused-deposition model 3D printing technique and warranting further exploration.Graphical

Development and characterisation of orally disintegrating flurbiprofen tablets using SeDeM-ODT tool.

In this study, SeDeM-ODT parametric tests were performed to determine the use of ludipress as a directly compressible tableting excipient for the development of a flurbiprofen orally disintegrating tablet. The preformulation features of different formulations (F1 -F9) were analyzed by the SeDeM-ODT tool which showed that all the powder blends were appropriate for direct compression since all the blends had index of good compressibility and bucodispersibility (IGCB) values above 5, signifying direct compression is the most appropriate method. The powder blend of the optimized formulation was assessed by the DSC-TGA technique. The optimization of nine different formulations blends of orally disintegrating tablets (ODTs) was prepared in various ratios by the implementation of design of experiments (DoE), using the central composite design by selecting ludipress (X1) (49-55%) and croscarmellose sodium (X2) (1-5%) while hardness, friability, and disintegration tests were selected as responses. The optimized formulations were evaluated by various tests and the results indicated that all the formulations were found to be in adequate range. Formulations were subjected to stability studies at accelerated states following ICH guidelines. Shelf life was found to be 51.144-56.186 months. Results of multiple-point dissolution studies revealed that formulations followed the Higuchi kinetic model. This study revealed that the SeDeM-ODT tool has been successfully used to determine the compression behavior of active compounds and their powder blends for the direct compression (DC) method in formulating flurbiprofen-ODT tablets.

Implementing the Design of Experiments (DoE) Concept into the Development of Mucoadhesive Tablets Containing Orange Peel Extract as a Potential Concept for the Treatment of Oral Infections.

This study explores for the first time the impact of chitosan (CS) with varying molecular weights (MW), orange peel extract concentration, and hydroxypropyl methylcellulose (HPMC) content on the formulation of buccal tablets for treating oral infections. Utilizing a statistical design of experiments (DoE), nine different formulations were evaluated for mechanical properties, dissolution behavior, mucoadhesion, and biological activity. A formulation with high CS MW, 60% orange peel extract, and 8% HPMC, emerged as the optimal formulation, demonstrating superior tabletability, compressibility, and compactibility. Dissolution studies indicated that hesperidin release followed the Higuchi model, with higher extract content enhancing this phenomenon. Mucoadhesion improved with increased HPMC and CS concentrations, although higher extract content reduced bioadhesion. Biological assays showed that higher extract levels boosted antioxidant activity, while CS primarily contributed to anti-inflammatory effects. The optimized formulation exhibited broad antimicrobial activity against key oral pathogens, surpassing the effectiveness of the individual components. Principal component analysis (PCA) further confirmed the significant influence of extract content on tablet properties. These findings suggest that the optimized tablet formulation holds promise for effective buccal delivery in the treatment of oral infections, warranting further investigation in clinical settings.

Optimized freeze-dried solid-dispersions boost naringin solubility, antibacterial and in-vitro anticancer activity

Naringin (NRG) is a water insoluble glycoside having wide range of therapeutic efficacy. Its efficacy is limited due to its poor water solubility and bioavailability. In the current research, solid dispersions (SDs) were prepared by freeze drying method using different carriers KollidonVA64, KollidonVA30, Soluplus and Poloxamer188. The prepared binary SDs were characterized for solubility and dissolution study to select the optimized composition and further ternary SDs was prepared with carrier blend (KollidonVA64 and Soluplus). Finally, the ternary SDs (F6) was evaluated for solid state characterization (DSC, XRD, SEM), drug polymer interaction (IR), in vitro antioxidant, antimicrobial as well as cell viability study against neuroblastoma cell. The binary SDs developed with KollidonVA64 and Soluplus showed greater solubility than KollidonVA30 and Poloxamer188. The ternary SDs (F6), showed a significant enhancement in the saturation solubility and dissolution than binary SDs (F1-F4). The binary SDs (F1-F4) displayed the maximum release in 120 min (73.5±2.8 to 94.6±3.1%), whereas the ternary SDs (F6) showed the maximum release in 60 min (99.2±1.6%). The spectroscopy results confirm the formation of a stable dispersion and no drug polymer interaction was observed. The thermogram, diffractogram and microscopic image confirms the conversion of crystalline NRG to amorphous form. These findings support the results of saturation solubility and dissolution data. The in vitro antioxidant, antimicrobial and cytotoxicity assessment displayed a greater activity of developed NRG SDs than the free NRG. The enhancement in the results may be due to the enhanced solubility of NRG after formation of SDs using the KollidonVA64 and Soluplus carrier blend.

Screening of Polymers for Oral Ritonavir Amorphous Solid Dispersions by Film Casting.

Background/Objectives: Drug-polymer interactions and miscibility promote the formation and performance of amorphous solid dispersions (ASDs) of poorly soluble drugs for improved oral bioavailability. The objective of this study was to employ drug-polymer interaction calculations and small-scale experimental characterization to screen polymers for potential ASDs of ritonavir. Methods: Seven polymers across four polymer types were screened as follows: an enteric one (EudragitS100), amphiphilic ones (HPMCAS-L, HPMCAS-H, and their 1:1 combination), hydrophilic ones (PEG-6000, PVP-VA), and a surfactant (Soluplus), including PVP-VA as a positive control, as the commercial ASD employs PVP-VA. Drug-polymer interaction calculations were performed for Hansen solubility parameter, Flory-Huggins parameter, and glass transition temperature. ASDs were prepared via film casting. Experimental characterizations included drug solubility in polymer solutions, polymer inhibition of drug precipitation, polarized light microscopy, differential scanning calorimetry, solubilization capacity, and dissolution studies. Results: HPMCAS-L, HPMCAS L:H, and Soluplus, along with the positive control PVP-VA, were identified as polymers for potential ASDs of ritonavir, with HPMCAS-L and PVP-VA being preferable. HPMCAS-L and the positive control PVP-VA were always viable for both 20% and 40% drug loads across all tests. Films with each of these four polymers showed improved dissolution compared to amorphous ritonavir without polymer. Drug-polymer interaction calculations anticipated the unfavorable small-scale experimental results for PEG-6000 and EudragitS100. Conclusion: Overall, the results contribute towards a resource-sparing approach to identify polymers for ASDs.

The role of coatings and plasticizers compatibility in stability of advanced gastro-resistant self-emulsifying pellets designed for the delivery of volatile compounds: A combined solid-state NMR and dissolution study

The gastro-resistant behaviour of solid self-emulsifying drug delivery systems (S-SEDDS) represents a significant and innovative advancement in delivering poorly soluble drugs. Due to the complexity of these systems and the liquid nature of SEDDS, thorough investigation is essential. This study explored the stability of self-emulsifying (SE) pellets containing the volatile compound thymol coated with gastro-resistant Eudragit® L 30 D-55 water dispersion. The SE pellet cores, composed of Neusilin® US2 with adsorbed SEDDS (thymol, triacylglycerol, Labrasol®, and propylene glycol), microcrystalline cellulose, and chitosan, were prepared using the extrusion/spheronization method and demonstrated optimal technological properties. The 6-month stability of three coating compositions, differing in thickness and triethyl citrate (TEC) concentration in the Eudragit® L topcoat, or the application of an ethylcellulose (EC, Surelease®) sub-coat, was investigated using the combined in vitro dissolution testing and solid-state nuclear magnetic resonance (ss-NMR) for detailed structural characterization. The dissolution data of samples with Eudragit® L topcoat data showed an acceleration of thymol release in acidic conditions, preventing the SE pellets from achieving gastro-resistance. The ss-NMR analysis revealed an incompatibility between TEC and SEDDS (specifically propylene glycol), identified as a TEC phase transition to a liquid phase independent of TEC concentration. Additionally, ss-NMR analysis revealed that neat thymol negatively affected coating layer stability by promoting the plasticization of Eudragit® L. The inclusion of a 10 % Surelease® sub-coat yielded positive results, maintaining the gastro-resistant properties of SE pellets stored under 25 °C/60 % RH for 6 months. However, ss-NMR analysis confirmed ongoing TEC liquefaction after 3 and 6 months, indicating that the oleic acid and triglycerides in Surelease® as plasticizers contributed to this instability. Therefore, this formulation cannot be deemed stable, and using Surelease® as a sub-layer is only a temporary solution. Overall, while plasticizers are commonly used in pharmaceutical technology, they can introduce significant problems in S-SEDDS development, and their use in sub- or topcoats should be carefully considered or avoided. At the same time, it became evident that in-vitro dissolution testing alone cannot capture the slow processes and interactions occurring within the internal structure of these systems.

Meloxicam-amino acids salts/ion pair complexes with advanced solubility, dissolution, and gastric safety

Amino acids have attracted attention as a potential functional excipient for optimizing biopharmaceutics characteristics of poorly soluble drugs. The amino acids are a diverse class with many functional groups, natural compounds, biocompatible, and low-molecular-weight substances. Two amino acids serine and arginine were investigated with meloxicam. Meloxicam has extremely low solubility; being NSAIDs, gastric upset, and ulcer are common side effects. Solid dispersions were produced by precipitation and physical mixing techniques. The produced combinations underwent in vitro dissolution, docking, DSC, FTIR, XRD, solubility, and gastric ulcer formation studies. Docking indicated ion pair/salt formation between the basic amino acid arginine and meloxicam. Both solubility and dissolution rates were increased by up to 3000-fold and 12-fold, respectively. DSC, FTIR an XRD supported these findings. Rats treated with meloxicam showed loss of surface gastric epithelium integrity and ulceration. The animal group received meloxicam: arginine showed intact gastric mucosa with the surface epithelium and gastric glands well organized and nearly similar to the untreated control. Arginine with the guanidine group that was capable of preserving gastric mucosa after repeated administration for 10 days. This study highlighted the role of arginine as a functional excipient that did not only improve solubility and dissolution rates but ameliorated the long-standing gastric side effects attributed to meloxicam.