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The conventional dosage forms (tablets, capsules) of ibuprofen have less potential in the suppression of pain and inflammation due to their slow dissolution rates and lower bioavailability. The aim of this study was to fabricate fibrous solid dispersion of ibuprofen for improved dissolution rate and quick therapeutic action. Drug-loaded microfibers were fabricated using centrifugal melt spinning (CMS) technique from the physical mixture of sucrose, ibuprofen and a hydrophilic polymer, PVP. These fibers were characterized by SEM, PXRD, DSC, and FTIR spectroscopy. The selected formulation was also pressed into tablets by direct compression method followed by its in vitro and in vivo characterization. The production yield of fibers was 75 ± 2% with an average diameter of 15 ± 5 µm. The drug loading efficiency (DLE) was 85 ± 5%. The tablets dissolved rapidly (<40 s). In vitro dissolution studies have shown >85% of ibuprofen dissolved from tablet within first 2 min which was ∼5 times quicker than drug alone. Dissolution efficiency has improved from 0.63 of ibuprofen to 0.95 of that in fibers with ∼7 times reduction in mean dissolution time. PXRD, and DSC have shown the amorphous state of ibuprofen in the formulation and FTIR spectra demonstrated no interaction of drug with excipients. In vivo anti-inflammatory studies using rabbits revealed a significant (p < 0.05) reduction in paw volume (mm) in the groups treated with fibrous formulation. This study concludes that microfibers produced by centrifugal melt spinning have improved dissolution rates and bioavailability of ibuprofen. Incorporation of polymer in the formulations improves the production yield and drug loading efficiency of microfibers. [ABSTRACT FROM AUTHOR]

Background: Owing to overcome the dissolution limited bioavailability of Meloxicam, the current research involves the development of Orodispersible films using Meloxicam by employing Quality by Design. Methods: In this work, the Meloxicam oral dispersible films were formulated by solvent casting method by altering three formulation factors viz. amount of film former, amount of the plasticizer, PEG 400 and type of film former (HPMC E3, HPMC E5, HPMC E15). Historical data designing under response surface methodology was selected as the experimental design. Disintegration time, dissolution of Meloxicam after 5 mins, folding endurance and tensile strength of the orodispersible films were taken as the responses. Results: All the formulations were found to have favorable tensile strength and folding endurance. The disintegration time values were found to be in a range of 9-15 sec, the values of amount of Meloxicam dissolved after 5 min were found to be in the range of 48-98%. The data obtained from the responses were statistically treated using ANOVA and the effect of the formulation factors were found to be significant. Conclusion: The optimization of these formulations indicated that a combined film former of 140mg of HPMC E15 and 50mg of HPMC E3 with 25mL plasticizer was found to be the optimized formulation. The films prepared at this combination showed disintegration time of 8 sec, drug release of 66.5% after 5 min which indicate that the formulated Meloxicam orodispersible films were successfully optimized and developed. [ABSTRACT FROM AUTHOR]

A significant proportion of recently approved drug molecules possess poor aqueous solubility which further restrains their desired bioavailability. Poor aqueous solubility of these drugs poses significant hurdles in development of novel drug delivery systems and achieving target response. Self-emulsifying drug delivery systems (SEDDS) emerged as an insightful approach for delivering highly hydrophobic entities to enhance their bioavailability. Conventional SEDDS were developed in a liquid form which owned numerous shortcomings like low stability and drug loading efficiency, fewer choices of dosage forms and irreversible precipitation of drug or excipients. To address these curbs solid-SEDDS (S-SEDDS) was introduced as an efficient strategy that combined advantages of solid dosage forms such as increased stability, portability and patient compliance along with substantial improvement in the bioavailability. S-SEDDS are isotropic mixtures of oil, surfactant, solvent and co-solvents generated by solidification of liquid or semisolid self-emulsifying ingredients onto powders. The present review highlights components of S-SEDDS, their peculiarities to be considered while designing solid dosage forms and various methods of fabrication. Lastly, key challenges faced during development, applications and future directions for the research in this area are thoroughly summarized. [Display omitted] • S-SEDDS combines the advantages of liquid- SEDDS and solid dosage form with greater stability, ease of manufacturing, dosage form variety and patient compliance. • Success of S-SEDDS from pharmacokinetic, pharmacodynamic, stability and industrial point of view • Challenges faced and future directions for the development of S-SEDDS [ABSTRACT FROM AUTHOR]

Objectives: The current objective of the present study was to enhance the solubility and dissolution rate of the antiviral drug atazanavir sulphate by employing nanocrystallization technique. Materials and Methods: The method employed for increment of solubility was nanocrystallization which is based on the reduction of particle size of the drug thereby increasing its solubility and also its dissolution property. Various polymers in different ratios were used like HPMC K15M, PVP K30 and PEG 6000. Results: Drug and polymers were firstly tested for their interaction between each other's and it was found that the drug and polymers are compatible with each other. From the solubility study it was seen that the solubility of the optimized batch was increased to 40.068mg/ml in distilled water and 160.182mg/ml in phosphate buffer while the pure drug shows the solubility of 4.174mg/ml in distilled water and 20.547mg/ml in phosphate buffer. The percent drug release of the optimized formulation was seen of 87.91% in 2 hrs which was maximum from all the other batches. The stability study revealed that the prepared nanocrystal does not show any insignificant changes and therefore it can be concluded as stable. Conclusion: The prepared nanocrystals are the proof that this method of nanocrystallization may prove to be an efficient method in increasing the solubility and dissolution rate of the drug which are having low solubility and low bioavailability. [ABSTRACT FROM AUTHOR]

Purpose: Oral drug delivery system has always been a preferred choice for the treatment of peptic ulcer and gastroesophageal reflux diseases. Being a proton pump inhibitor omeprazole restricts gastric acid secretion but the foremost downside is its degradation in acidic environments. The systemic absorption of gastro-unstable drugs can be improved by the enteric coating. Materials and Methods: This study was aimed at developing an effective enteric coating for omeprazole tablets using HPMC E5-LV and Hydroxypropyl Methylcellulose Acetate Succinate (HPMC-AS) polymers. The core tablets were subcoated with HPMC E5-LV which acted as a barrier between core tablet and enteric coated tablet. The enteric coating was applied using HPMC-AS. Results: Dissolution information unveiled that the enteric coat remained in place for 2 hr in acidic medium (0.1N HCl) and later dissolved when came in contact with basic media (acetate buffer pH 6.8), it dissolved within a jiffy. Conclusion: The release profile showed 91 to 98% drug release within 1hr in pH 6.8 Acetate buffer. Further instrumental analysis was performed to ascertain drug-polymer interaction. [ABSTRACT FROM AUTHOR]

In this study, an attempt was made to produce Liqui-Tablets for the first time. This was carried out through the compaction of naproxen Liqui-Pellets. The incentive to convert the novel Liqui-Pellet into Liqui-Tablet was due to the array of inherent advantages of the popular and preferred tablet dosage form. The study showed that naproxen Liqui-Tablet could be successfully produced and the rapid drug release rate (100% drug release ~ 20 min) could be achieved under pH 1.2, where naproxen is insoluble. It was observed that the different pH of the dissolution medium affected the trend of drug release from formulations with varying amounts of liquid vehicle. The order of the fastest drug-releasing formulations was different depending on the pH used. The presence of Neusilin US2 showed considerable enhancement in the drug release rate as well as improving Liqui-Tablet robustness and hardness. Furthermore, images from X-ray micro-tomography displayed a uniform distribution of components in the Liqui-Tablet. The accelerated stability studies showed acceptable stability in terms of dissolution profile. [ABSTRACT FROM AUTHOR]

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.

Tadalafil (TDL) is a phosphodiesterase-5 inhibitor (PDE5I), indicated for erectile dysfunction (ED). However, TDL exhibits poor aqueous solubility and dissolution rate, which may limit its application. This study aims to prepare amorphous solid dispersion (ASD) by spray-drying, using glycyrrhizin-a natural drug carrier. Particle and physicochemical characterizations were performed by particle size, polydispersity index measurement, yield, drug content estimation, Fourier Transformed Infrared (FTIR) spectroscopy, Differential scanning calorimetry (DSC), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and dissolution study. In order to evaluate the aphrodisiac activity of the prepared ASD, sexual behavior study was performed in male rats. It is further considered for the stability study. Our results revealed that TDL-GLZ spray-dried dispersion was a successful drug-carrier binary mixture. XRD and SEM showed that ASD of TDL with GLZ presented in the amorphous state and dented-spherical shape, unlike the drug indicating crystalline and spiked shaped. The optimized ASD3 formulation with particle size (1.92 µm), PDI (0.32), yield (97.78%) and drug content (85.00%) showed 4.07 folds' increase in dissolution rate compared to pure TDL. The results obtained from the in vivo study exhibit significantly improved aphrodisiac activity with ASD3. The stability study revealed that the prepared ASD3 did not show any remarkable changes in the dissolution and drug content for 1 month storage at room temperature. [ABSTRACT FROM AUTHOR]

Aim: Self nano-emulsifying drug delivery system (SNEDDS) of candesartan cilexetil was explored to enhance its oral bioavailability. SNEDDS has tremendous potential in enhancing oral bioavailability of poorly aqueous soluble therapeutic agents. SNEDDS are pre-concentrate mixture of oil, surfactant and co-surfactant produces nanoemulsion after oral administration due to mild agitation produced by gastro motility within the size range of 20-200nm. Methodology: The formulations were developed by selecting capmul MCM®, triacetin® and caprylic acid® under the oil phase based on solubility of drug; cremophore RH40®, brij35® under surfactants category and transcutol P under co-surfactant on basis of their emulsification property. Optimum concentrations were choosen from the Terinary phase diagrams and evaluated for their properties. Results: From the results of ternary diagrams 16 formulations were selected (A1, A2, A3, A4, B1, B2, C1, C2, C3, C4, D1, D2, E1, E2, F1, F2) and subjected to characterization studies. Best formulations were subjected to particle size analysis and in vitro release studies. Among selected formulations, A1 and C1 have shown high in vitro drug release profiles with less selfemulsification time having grade A dispersibility without any precipitation and phase separation. Discussion: Concentration of surfactant helps in reducing the size of the particle when compared to the co-surfactant concentration. Enhanced dissolution of candesartan cilexitil may be attributed to the spontaneous formation of nanoemulsion in vitro with a decreased particle size that leads to the increased surface area leaving the drug candesartan as finely dispersed particles in dissolution media. Conclusion: Formulation C1 consists of triacetin oil 30% w/w, cremophore RH 40 6%w/w and transcutol P 64%w/w showed best emulsification characteristics like 99% percent transmittance, with increased dissolution profile (98%) than pure drug (45%) with nano range goblet size (165.9nm). [ABSTRACT FROM AUTHOR]

Anionic biopolymer (sodium alginate/low-methoxyl pectin/gellan gum) coated carboxymethyl pullulan-ZnO nanocomposites encapsulating erlotinib were developed for lung cancer therapy. The thermal, X-ray and infrared analyses suggested an environment in the nanocomposites compatible with the drug, except certain degree of attenuation in drug's crystallinity. SEM studies revealed the irregular morphology of the nanocomposites. The uncoated and coated formulations demonstrated excellent drug encapsulation efficiency and pH dependent dissolution behavior, which was significantly improved as compared to pristine drug. The drug release profiles of the core-shell nanocomposites (F-4) in acidic and neutral media were best fitted in Korsemeyer-Peppas and zero-order kinetic model, respectively. [ABSTRACT FROM AUTHOR]

Aim Liqui-Pellet is potentially an emerging next-generation oral pill, which has shown promising results with unique advantages as well as displaying potential for commercial feasibility. Since Liqui-Pellet technology is still in its infancy, it is important to explore the parameters that can affect its performance, particularly the drug release rate. Therefore, the aim of this study is to investigate thoroughly the effect of Avicel PH101 (carrier) and Aerosil 300 (coating material) ratio (R-value) in Liqui-Pellet. Methods Key parameter for Liqui-Pellet formulation in this study was the ratio of carrier and coating material. Tests were carried out to assess the physicochemical properties of different formulations. This involved looking into particle size, robustness, flowability, solid-state and drug release profile. The morphology of Liqui-Pellet was investigated by SEM. Results It is found that R-value does not have a major effect on the success of Liqui-Pellet production. However, R-value does seem to have an effect on Liqui-Pellet size at a certain water content level and a slight effect on the drug release rate. A decrease in Avicel PH101 concentration and an increase in Aerosil 300 concentration in Liqui-Pellet formulations can reduce Liqui-Pellet size and slightly increase drug release rate by 9% after 2 h. The data shows Liqui-Pellet is resistant to friability, able to achieve exceptional flow property and have smooth surfaces, which is critical for applying coatings technology. Such properties are ideal in terms of commercial manufacturing. The XRPD and DSC both show the reduction in formulation crystallinity, which is expected in Liqui-Pellet formulation as a result of solubility of the drug in the co-solvent used in the preparation of Liqui-Pellets. Conclusion Overall it seems that R-value can affect Liqui-Pellet drug release rate and size but not on the production success rate. [ABSTRACT FROM AUTHOR]

It was evident from the literature that mesoporous silica nanoparticles can be a suitable drug carrier system because of biocompatibility, drug loading capacity; targeting ability and tunable porosity. This investigation was aimed to synthesize mesoporous silica carriers by sol-gel method using tetraethyl orthosilicate as precursor and cetyl trimethyl ammonium bromide and cetylpyrridinium chloride as a pore generating agent. Initially the effect of molar concentrations of cationic surfactants on the pore size of porous nanoparticles was studied followed by loading of repaglinide onto the surface as well as inside the pores of nanoparticles by solvent immersion method. The loaded mesoporous silica nanoparticles were evaluated for % drug loading and in vitro release. Techniques including N2-adsorption-desorption isotherm, x-ray diffractometry, scanning electron microscopy were used for characterization. The drug loading (90.3±0.25%) was observed highest in case of nanoparticles prepared with and cetyl trimethyl ammonium bromide than that of cetylpyrridinium chloride. The drug release was found 96.5±1.15% which was more than that of pure drug and marketed formulation. The results revealed drug loading with slight decrease in crystallinity of drug in mesoporous silica nanoparticles. The particles were spherical in shape with smooth surface. In conclusion the mesoporous silica nanoparticles had shown increased dissolution because of increased surface area. [ABSTRACT FROM AUTHOR]

With the advent of high throughput screening, drugs are emerging to be more lipophilic and less hydrophilic. Liquisolid Technology aims at solubility enhancement of such entities via cosolvency concept in a relatively minimalistic setup where there is no need of sophisticated machinery and is cost effective. It involves constituting a drug into molecular dispersion via a non-volatile solvent and then transforming it into a dry looking, free flowing compressible powder. This article aims at mapping Liquisolid Technology where its preparation techniques and potential applications are reviewed. An overview of the performance of Liquisolid in areas of dissolution enhancement, zero order release, photostability enhancement, liquipellets and its role in natural product formulations is recorded for a number of drugs. [ABSTRACT FROM AUTHOR]

A target of best dissolution improvement of poorly soluble drugs is a necessity for the success of formulation in industry. The present work describes the preparation, optimization, and evaluation of a new spherical agglomeration technique for glimepiride as a model of poorly soluble drugs. It involved the emulsification of a drug solution containing a dispersed carrier that tailors the crystal habit of the drug to a perfect spherical geometry, in a poor solvent containing a hydrophilic polymer which imparts sphericity and strength to the formed agglomerates. The FTIR peaks of optimized product did not show any sign of chemical interaction between the drug and adsorbed carrier. The DSC and X ray diffractogram showed a peak characteristic of spherical agglomerates with much less intensity than that of glimepiride. The dissolution t1/2 of the drug slightly decreased from 381 min to 334 min in plain agglomerates. Introducing polymers in the aqueous phase of emulsion led to an improvement in the dissolution, reflected in t1/2 ranging from 118 to 231 min. Agglomerates prepared with Starlac/PVP demonstrated the most optimum physicochemical characteristics being spherical, with the best flowability and packability parameters. The t1/2 was as short as 19 min. The new carrier/polymer system offered a synergistic combination that highly contributed in dissolution enhancement of glimepiride. The spheronization and amorphisation offered by the new technique could account for such improvement. [ABSTRACT FROM AUTHOR]

The objective of this study is to enhance the dissolution properties of leflunomide, a class BCS-II drug by incorporating the self emulsifying (SE) form of the drug onto liquisolid systems in the form of tablets. Different formulae were prepared by dissolving leflunomide in PEG300 then forming SE systems using tween 80 as surfactant and either sesame oil and paraffin oil then adsorbing on powder excipients to form SE liquisolid powders. The prepared powders showed adequate flowability. The drug and excipients showed compatibility by analysis with DSC, XRD and FTIR. After compression, all tablets showed adequate weight variation, friability and disintegration time with disintegration time ranging between 8.45 ± 0.16 min and 10.7 ± 0.29 min. All liquisolid tablets exhibited higher in vitro dissolution in distilled water compared to physical mixture and the commercial tablets (Arthfree®) with formula containing sesame oil and highest amount of solvent (TS04) exhibiting the highest dissolution profile and it did not change by the change in the pH of the dissolution medium. The tablets showed stability during a 6 months accelerated stability study according to appearance, drug content, disintegration time and dissolution profile. Thus it can be concluded that combining self emulsifying drug delivery technique and liquisolid technology can be a promising tool to enhance the dissolution profile of leflunomide in vitro.

The current study explored the twin-screw melt granulation (TSMG) as a potential technology for the water solubility enhancement of biopharmaceutical classification system (BCS) class II drugs. As a model drug, carbamazepine (CBZ) was formulated with three different polymers as melt granules produced in a co-rotating twin-screw granulator. Polyethylene glycol 6000 (PEG 6000) and Kolliphor® (poloxamer) P407 were used as binding materials at two different granulation temperatures (T max : 70 °C; 100 °C). Additionally, Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) was chosen as binder of higher melting/ granulation temperature (T max : 140 °C). Temperature dependent polymorphic transition of CBZ during melt granulation was observed and identified using XRPD- (X-ray powder diffraction) and FTIR- (Fourier transform infrared spectroscopy) analysis. The effects of polymer type, polymer content (10, 15, 20% (w / w)) and granulation temperature on polymorphic transition, their impact on wettability (contact angle via drop shape-analysis), and the resulting dissolution performance at non-sink conditions in phosphate buffer (pH 6.8), were studied. This study showed that TSMG led to a crystalline system facilitating supersaturation when brought in solution, even when high drug loads (up to 90% (w/w)) were used. In general, for all granules produced, the supersaturation level and its duration varied with the extent of polymorphic transition and binder concentration. The results of this study indicated the importance of temperature control and polymer selection for tailoring desired dissolution profiles. [ABSTRACT FROM AUTHOR]

Liqui-pellet is a new dosage form stemming from pelletisation technology and concept from liquisolid technology. In spite of liqui-pellet overcoming a major hurdle in liquisolid technology through achieving excellent flow property with high liquid load factor, the formulation requires to be optimised in order to improve drug release rate. Liqui-pellets of naproxen containing Tween 80, Primojel, Avicel and Aerosil were extruded and spheronised. Flowability test confirmed that all liqui-pellet formulations have excellent-good flow property (Carr's index between 3.9–11.17%), including liqui-pellets with a high liquid load factor of 1.52, where 38% of the total mass is co-solvent. This shows a relatively high liquid load factor can be achieved in liqui-pellet without compromising the flowability, which is one of the key novelty of this work. It was found that the improved drug release rate was due to the remarkably improved disintegration of the supposedly non-disintegrating microcrystalline-based pellet; the optimised liqui-pellet seems to explode into fragments in the dissolution medium. At pH 1.2, the optimised formulation had ~ 10% more drug release than non-optimised formulation after 2 h, and at pH 7.4, the drug release of the optimised pellet was nearing 100% at ~ 15 min, whereas the none-optimised pellet only achieved ~ 79% drug release after 2 h. DSC and XRPD indicated an increase in the dissolution rate could be due to molecularly dispersion of naproxen in the pellets. Overall results showed that liqui-pellet exhibited an enhanced drug release and the capacity for high liquid load factor whilst maintaining excellent flowability, rendering it a potentially commercially feasible drug delivery system. [ABSTRACT FROM AUTHOR]

The objective of the present study was to enhance the dissolution rate of carvedilol (CA), a poorly water-soluble antihypertensive drug, using a co-grinding method in the presence of polyvinylpyrrolidone (PVP) and sodium lauryl sulfate (SLS). Various ratios of CA:PVP:SLS were ground by a planetary ball mill. They were studied in terms of dissolution, solubility, and particle size. The solid state and morphology of the intact drug and prepared samples were also characterized using differential scanning calorimetry (DSC), infrared spectroscopy (IR), X-ray diffraction (XRD), and scanning electron microscope (SEM). According to the results, co-grinding in the presence of PVP and SLS significantly increased CA dissolution rate. DE60 (dissolution efficiency) obtained for the best ternary ground mixture (89.31%) was 3.4 and 4.5 times higher than that of the related physical mixture (PM) and the intact drug, respectively. Further, the solubility of this formulation was about 10 times higher compared to that of the intact CA. A direct correlation was also observed between the chamber rotation speed of the planetary mill within the range of 100–400 rpm and CA dissolution rate. Finally, DSC, IR, and XRD analysis ruled out any polymorphic changes and chemical interactions during the grinding process. [ABSTRACT FROM AUTHOR]

The main aim of this study was to enhance the dissolution rate of BCS class II drug Indomethacin (IND) by solid dispersion (SD) techniques using Ocimum basilicum mucilage (OBM) as a carrier. Solid dispersions of indomethacin were prepared by using Ocimum basilicum mucilage by four different methods. Effect of methods of preparation on dissolution rate was studied. It was found that the dissolution rate of IND from its SD was dependent on the method of preparation of solid dispersions. Dissolution study revealed that the physical mixture and kneading method were convenient and effective methods for dissolution enhancement of poorly water soluble drug IND, among various methods of preparation of SD. The prepared SD's were characterized by FTIR, Differential Scanning Calorimetry, and X-ray diffraction studies. From the study we conclude that OBM could be used as a potential carrier in enhancing the dissolution rate and ultimately bioavailability of IND. [ABSTRACT FROM AUTHOR]

Objectives: The present work aim to identify the process parameters and technical parameters of granules that affect the disintegration time of an IR tablet. There by utilizing this knowledge to develop an IR tablet without any Super Disintegrants (SD). Methods: The experiments were designed using Design-Expert®. A two factorial design at two levels (-1, + 1) were selected. The study evaluated the effect of particle size and Binder concentration (BC) on Disintegration Time (DT), Hardness and Compressibility index (CI). Discussion: The CI below 16% can be achieved for the granules prepared with particle size > 670µ m and binder concentration> 18.56mg for PVP K 30. The particle sizes do not possess any impact on disintegration time. The granules prepared at the 250µ size and 600µ size shoes similar disintegration time. However, the particle size affects hardness and CI. The BC has a strong impact on hardness, CI and DT. Even though the particle size does not have a direct impact on DT, it affects the hardness, which has a greater impact on DT. Conclusion: The study identified the technical methods and suggests certain formula to attain the low disintegration time, excellent hardness for an IR tablet and fair flow property for the prepared granules. The particle size has a direct impact on the hardness of the tablet. The formula serves as an excellent alternative for SD at an industrial level, to make the drug product more economical and more effective. [ABSTRACT FROM AUTHOR]

Piroxicam-CMSC solid dispersions were produced by spray drying from aqueous solvents. Depending on the drug-polymer ratio, loading and entrapment efficiency of CMSC microparticles were 6.8–46.75 and 40.79–60.35% w/w, respectively. Scanning electron microscopy revealed non-spherical geometry and agglomeration of the spray-dried particles. The average size of the particles ranged from 7 to 170 µm. Infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction confirmed intact crystalline piroxicam in the microparticles. In gastric pH, microparticles and native piroxicam have shown less than 25% and more than 45% of drug dissolution, respectively in 2 h. In contrast, at pH 7.4, microparticles have shown 80% of drug dissolution; whereas native piroxicam achieved only 30% of dissolution by 30 min. The spray-dried CMSC particles are efficient in restricting drug release in gastric pH and enhance drug dissolution in intestinal pH. The method is eco-friendly as it uses aqueous solvents and non-toxic materials. [ABSTRACT FROM AUTHOR]

Bicalutamide (BCT), an anticancer drug, suffers from dissolution rate limited bioavailability and poor micromeritic properties. Spherical crystallization involves the formation of spherical agglomerates with enhanced dissolution properties, obviating the need for further granulation process. The present investigation was focused on spherical agglomeration of BCT by quasi-emulsion solvent diffusion method. All the responses were subjected to principal component analysis to scrutinize the critical attributes. Further for optimization, X1; influence of phase ratio, X2; amount of PEG 6000 and X3; stirring speed on critical dependent variables was studied by employing the Box-Behnken experimental design. The agglomerates exhibited better flow properties, higher bulk density, and improved compressibility compared to pure powder drug. In-vitro release studies revealed enhancement of dissolution properties of poorly soluble BCT. Characterization studies carried out by differential scanning calorimeter and powder X-ray diffractometer revealed crystallinity of drug with decreased intensity in the formulation. Scanning electron microscopy showed spherical shape agglomerates of BCT. The residual solvents were largely below the permitted limits. Spherical agglomerates demonstrated enhanced dissolution properties on account of reduced particle size and partial conversion into amorphous form. Thus, spherical agglomerates of BCT seem to be a promising approach to ameliorate the dissolution properties which might thereby improve its bioavailability. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Corona alternating current electrospinning (C-ACES), a scaled-up productivity electrospinning method was developed by combining the intense forces of the alternating electrostatic field and a sharp-edged spinneret design with increased free surface. C-ACES reached two orders of magnitude higher productivity (up to 1200 mL/h) than the classical single needle direct current electrospinning (DCES) without any alteration of fiber properties. Polyvinylpyrrolidone K90 (PVPK90), a water soluble high molecular weight nonionic polymer was processed for the first time with single needle alternating current electrospinning (ACES) and C-ACES in order to prepare fast dissolving amorphous solid dispersions of spironolactone (SPIR), a poorly water-soluble antihypertensive model drug. The limited spinnability of PVPK90 with AC high voltage could only be resolved by optimizing the solution conductivity with organophilic salts such as sodium dodecyl sulfate (SDS) demonstrating the importance of conductivity during ACES. The effects of varied solution properties (composition and conductivity) and scaling-up were investigated by SEM imaging. Solid state analyses revealed that SPIR was dispersed in an amorphous form in the fibrous mats. In vitro dissolution tests showed ultrafast drug release in case of the amorphous formulations even when prepared with scaled-up C-ACES. Besides the enhancement of conductivity SDS also prevents SPIR from precipitation from the dissolution media due to its solubilization ability. [ABSTRACT FROM AUTHOR]

Most of the newly developed drug candidates are lipophilic and poorly water-soluble. Enhancing the dissolution and bioavailability of these drugs is a major challenge for the pharmaceutical industry. Liquisolid technique, which is based on the conversion of the drug in liquid state into an apparently dry, non-adherent, free flowing and compressible powder, is a novel and advanced approach to tackle the issue. The objective of this article is to present an overview of liquisolid technique and summarize the progress of its applications in pharmaceutics. Low cost, simple processing and great potentials in industrial production are main advantages of this approach. In addition to the enhancement of dissolution rate of poorly water-soluble drugs, this technique is also a fairly new technique to effectively retard drug release. Furthermore, liquisolid technique has been investigated as a tool to minimize the effect of pH variation on drug release and as a promising alternative to conventional coating for the improvement of drug photostability in solid dosage forms. Overall, liquisolid technique is a newly developed and promising tool for enhancing drug dissolution and sustaining drug release, and its potential applications in pharmaceutics are still being broadened.

In the present work, the porous metal-organic framework (MOF) Basolite®F300 (Fe-BTC) was tested as a potential drug-releasing depot to enhance the solubility of the anticancer drug paclitaxel (PTX) and to prepare controlled release formulations after its encapsulation in amphiphilic methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) nanoparticles. Investigation revealed that drug adsorption in Fe-BTC reached approximately 40%, a relatively high level, and also led to an overall drug amorphization as confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The dissolution rate of PTX-loaded MOF was substantially enhanced achieving a complete (100%) release within four days, while the neat drug only reached a 13% maximum rate (3–4 days). This PTX-Fe-BTC nanocomposite was further encapsulated into a mPEG-PCL matrix, a typical aliphatic amphiphilic copolyester synthesized in our lab, whose biocompatibility was validated by in vitro cytotoxicity tests toward human umbilical vein endothelial cells (HUVEC). Encapsulation was performed according to the solid-in-oil-in-water emulsion/solvent evaporation technique, resulting in nanoparticles of about 143 nm, slightly larger of those prepared without the pre-adsorption of PTX on Fe-BTC (138 nm, respectively). Transmission electron microscopy (TEM) imaging revealed that spherical nanoparticles with embedded PTX-loaded Fe-BTC nanoparticles were indeed fabricated, with sizes ranging from 80 to 150 nm. Regions of the composite Fe-BTC-PTX system in the infrared (IR) spectrum are identified as signatures of the drug-MOF interaction. The dissolution profiles of all nanoparticles showed an initial burst release, attributed to the drug amount located at the nanoparticles surface or close to it, followed by a steadily and controlled release. This is corroborated by computational analysis that reveals that PTX attaches effectively to Fe-BTC building blocks, but its relatively large size limits diffusion through crystalline regions of Fe-BTC. The dissolution behaviour can be described through a bimodal diffusivity model. The nanoparticles studied could serve as potential chemotherapeutic candidates for PTX delivery.

Despite the wide-spread use of liposomal drug delivery systems, application of these systems for oral purposes is limited due to their large-scale formulation and storage issues. Proliposomes are one of the formulation approaches for achieving solid powders that readily form liposomes upon hydration. In this work, we investigated a dry powder formulation of a model low-soluble drug with phospholipids loaded in porous functionalized calcium carbonate microparticles. We characterized the liposome formation under conditions that mimic the different gastrointestinal stages and studied the factors that influence the dissolution rate of the model drug. The liposomes that formed upon direct contact with the simulated gastric environment had a capacity to directly encapsulate 25% of the drug in situ. The emerged liposomes allowed complete dissolution of the drug within 15 min. We identified a negative correlation between the phospholipid content and the rate of water uptake. This correlation corroborated the results obtained for the rate of dissolution and liposome encapsulation efficiency. This approach allows for the development of solid proliposomal dosage formulations, which can be scaled up with regular processes.

Fenofibrate-loaded electrospun microfibrous sheets were prepared in an attempt to enhance the dissolution of the poorly soluble antihyperlipidemic agent and to improve its bioavailability. Physicochemical changes that appeared during the electrospinning process were monitored using a wide array of solid-state characterization techniques, including attenuated total reflectance Fourier-transformed infrared spectroscopy and positron annihilation lifetime spectroscopy, while fiber morphology was monitored via scanning electron microscopy. Dissolution studies carried out both in 0.025 M sodium dodecyl sulfate and in water revealed an immediate release of the active agent, with an approximately 40-fold release rate enhancement in water when compared to the micronized active agent. The dramatic increase in dissolution was attributed partially to the amorphous form of the originally crystalline active agent and the rapid disintegration of the electrospun microfibrous sheet due to its high surface area and porosity. The obtained results could pave the way for a formulation of the frequently used antihyperlipidemic agent with increased bioavailability.

It has been observed that most of the chemical entities have high lipophilicity and poor aqueous solubility, which result in poor bioavailability. In order to improve the bioavailability, the release behavior of such drugs should be improved. Although there are numerous techniques to handle solubility related issue, but they are expensive due to involvement of complicated equipments, advanced manufacturing operations that includes multiple and tedious steps. The liquisolid technology or powder solution technology is a promising technique for modifying the release characteristics of active pharmaceutical ingredients. As the liquisolid technology uses similar production processes as followed to develop a conventional tablet, but this technology to improve the release rate of poorly water soluble drugs is simple and cost effective The core concept of the technique involves, liquids such as solution/dispersion of poorly soluble drugs in a non-volatile solvent that is transformed into free flowing and desirable compression characteristics. To develop a fast-release liquisolid formulation, high amount of liquid vehicle is required while more effective tableting excipients with high liquid adsorption are needed to reduce the weight of the tablet. Simultaneously, this technology also has the capability to sustain the drug release and allow the development of sustained release formulation with desirable release kinetics. The present work deals with the chronological compilation and briefing of all the reported researches which involved the concept of underlined technology by the use of common as well as novel excipients to modify the release behavior of therapeutically active compounds.

Recently, it has been observed that newly developed drugs are lipophilic and have low aqueous solubility issues, which results in a lower dissolution rate and bioavailability of the drugs. To overcome these issues, the liquisolid technique, an innovative and advanced approach, comes into play. This technique involves the conversion of the drug into liquid form by dissolving it in non-volatile solvent and then converting the liquid medication into dry, free-flowing, and compressible form by the addition of carrier and coating material. It offers advantages like low cost of production, easy method of preparation, and compactable with thermo labile and hygroscopic drugs. It has been widely applied for BCS II drugs to enhance dissolution profile. Improving bioavailability, providing sustained release, minimizing pH influence on drug dissolution, and improving drug photostability are some of the other promising applications of this technology. This review article presents an overview of the liquisolid technique and its applications in formulation development., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

CThe objective of the present study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing Capryol-90 as oil phase for the delivery of Embelin, a poorly water soluble herbal active ingredient. Box-Behnken experimental design was employed to optimise the formulation variables, X1 (amount of oil; Capryol 90), X2 (amount of surfactant; Acrysol EL 135) and X3 (amount of co-surfactant; PEG 400). Systems were appraised for visual characteristics for self emulsifying time, globule size and drug release. Optimised liquid formulations were formulated into free flowing granules (S-SNEDDS) by adsorption on the porous materials like Aerosil 200 and Neusilin and thereby compressed into tablet. In vitro dissolution studies of SNEDDS revealed increased in the dissolution rate of the drug. FT-IR data revealed no physicochemical interaction between drug and excipients. Solid state characterization of S-SNEDDS by DSC and Powder XRD confirmed reduction in drug crystallinity which further supports the results of dissolution studies. TEM analysis exhibited spherical globules. Further, the accelerated stability studies for 6 months revealed that S-SNEDDS of Embelin are found to be stable without any significant change in physicochemical properties. Thus, the present studies demonstrated dissolution enhancement potential of porous carrier based S-SNEDDS for poorly water soluble herbal active ingredient, Embelin.

Abstract An orally dissolving web (ODW) formulation of poorly soluble carvedilol (CAR) was developed and manufactured continuously using electrospinning (ES) as a key technology. Phase solubility tests revealed that hydroxypropyl-β-cyclodextrin (HPβCD) solubilizer alone cannot ensure sufficient solubility (6.25 mg CAR in 20 mL) in the oral cavity even if citric acid was present to ionize the basic drug. In turn, electrospun amorphous nanofibers of polyvinylpyrrolidone K30 (PVPK30) and CAR exhibited notable supersaturation of the drug in the presence of citric acid. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) confirmed the amorphous state of CAR. The final ODW was prepared by layering the nanofibers onto pullulan, a well-soluble polysaccharide film carrying citric acid. The double-layered formulation showed ultrafast disintegration and dissolution modeling the oral cavity meeting regulatory requirements (<30 s). The continuous production was accomplished using our recently developed continuous model system by controlled deposition of the nanofibers onto the carrier film strained to a wheel collector and followed by cutting into final dosage units. Performance tests of the continuous system revealed satisfactory content uniformity over time (average acceptance value = 9.45), while residual solvent content measurements showed trace amounts of ethanol (EtOH) after production and acceptable dimethyl-formamide (DMF) content with secondary drying at room temperature. The presented work demonstrates how ES can be part of a continuous manufacturing system as an advanced drying tool during the formulation of challenging drugs. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Curcuma comosa (C. comosa) is a Thai medicinal herb that provides numerous pharmacologic activities due to its estrogen-like action. This study aimed to investigate the use of liquisolid technique to prepare tablets containing oleoresin-like crude extract of C. comosa, and to improve the dissolution profiles of its major compounds, diarylheptanoids (DAs). Free flowing powders of C. comosa extract were obtained by adsorption onto solid carriers, microcrystalline cellulose, with colloidal silica as coating material. FTIR results ruled out possible interactions between C. comosa extract and excipients. The results indicated that all of liquisolid tablets met the USP requirements. The release of DAs were significantly increased through liquisolid formulations, compared to crude extract. By decreasing the ratio of carrier to coating from 20 to 10, an improvement in dissolution rate was observed. Addition of additives - namely polymer (polyvinyl pyrrolidone) and/or nonvolatile liquid (propylene glycol) affected tablet properties which involved longer disintegration time and lower DA dissolution. Optimized C. comosa liquisolid formulation was prepared in a carrier to coating ratio of 10 without additives. Stability studies showed that physical properties of liquisolid tablet were not affected by aging, but percent remaining and dissolution profiles of DAs were influenced by storage temperature. In vivo pharmacokinetic behavior of the optimized C. comosa liquisolid tablets was investigated following a single oral administration to rabbits. The results proved that the method used for preparation of liquisolid led to C. comosa tablets with low variation in content uniformity and tablet properties, as well as enhanced dissolution behavior. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Wet milled suspensions of ITZ with various types/molecular weights of polymers. • Spray-dried the suspensions, forming 60–78% ITZ-loaded nanocomposites. • HPC was more effective than HPMC and PVP in stabilizing ITZ nanosuspensions. • Polymers with low molecular weight led to slow ITZ release from nanocomposites. • Demonstrated surfactant-free, immediate release nanocomposites with HPC SL/L. Abstract We explore the impact of various polymers and their molecular weight on the stabilization of wet-milled suspensions of itraconazole (ITZ), a poorly soluble drug, and its dissolution from spray-dried suspensions. To this end, ITZ suspensions with SSL, SL, and L grades of hydroxypropyl cellulose (HPC) having molecular weights (MWs) of 40, 100, and 140 kg/mol, respectively, hydroxypropyl methyl cellulose (HPMC E3 with 10 kg/mol), polyvinylpyrrolidone (PVP K30 with 50 kg/mol), sodium dodecyl sulfate (SDS, surfactant), and HPC SL–SDS were wet media milled and spray-dried. Laser diffraction results show that 2.5% HPC SL–0.2% SDS led to the finest ITZ nanosuspension, whereas without SDS, only 4.5% HPC with SL/L grades ensured minimal aggregation. Rheological characterization reveals that aggregated suspensions exhibited pronounced pseudoplasticity, whereas stable suspensions exhibited near Newtonian behavior. Spray-drying yielded nanocomposites with 60–78% mean ITZ loading and acceptable content uniformity. Severe aggregation occurred during milling/drying when 4.5% polymers with MW ≤ 50 kg/mol were used; their nanocomposites exhibited incomplete redispersion due to slow matrix erosion and released ITZ slowly during dissolution test. Overall, high drug-loaded, surfactant-free ITZ nanocomposites that exhibited immediate release (>80% dissolved in 20 min) were prepared via spray-drying of wet-milled ITZ with 4.5% HPC SL/L. [ABSTRACT FROM AUTHOR]

It is hypothesized that a novel crystalline solid dispersion (CSD) of docetaxel (C-DXT) can be engineered by dispersing native docetaxel (DXT, a BCS class II drug) in sodium acetate crystal (SA). DXT is dissolved in glacial acetic/SA solution and freeze-dried. The resulting C-DXT is characterized by differential scanning calorimetry (DSC), powder X-ray analysis (PXRD), LC-MS/MS, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Quartz crystal microbalance with dissipation monitoring (QCM-D) and dynamic light scattering (DLS). Its cytotoxicity on model cancerous (MCF-7, MDA-MB-468) and normal breast cells (MCF-10A) is assessed by MTS assay. SEM/TEM data and the absence of the characteristics peaks of DXT on the DSC curve (at 193.4 °C) and the XRD scan (at 2θ = 15.31 °C and 23.04 °C) confirm the presence of C-DXT in SA. The LC-MS/MS data indicates the chemical stability of DXT. The yield and C-DXT loading are 95.2% and 6.52% w/w, respectively. The C-DXT rapidly forms an aqueous non-rigid nanosuspension with a faster drug dissolution rate compared to native DXT. Unlike, control Tween 80/ethanol, SA is noncytotoxic to normal cells. However, C-DXT’s cytotoxicity is time and dose dependent for all diseased cells. This unique CSD process might be applicable to other hydrophobic bioactive agents to enhance their safety and efficacy. [ABSTRACT FROM AUTHOR]

Curcumin (CUR) solutions prepared with α-glucosyl stevia (Stevia-G) and polyvinylpyrrolidone K-30 (PVP) by evaporation method showed 11,000-fold higher solubility compared to CUR alone. Tri-component formulations of CUR/Stevia-G/PVP in aqueous solution showed improved CUR stability for precipitation-triggering conditions of CUR, such as aqueous dilution and temperature changes. Fluorescence study with CUR and pyrene indicated that Stevia-G/PVP mixed solutions produce a more hydrophilic microenvironment around their molecules with increasing PVP concentration compared to Stevia-G solution alone. These results suggested the composite formation associated with the adsorption of the aggregated structure of Stevia-G onto PVP molecules. Jelly formulations were prepared with κ-carrageenan, and jelly formulations containing nanocomposites formed by CUR/Stevia-G/PVP obviously enhanced the dissolution properties of CUR compared to CUR powder. This result indicated that the composite formed by CUR/Stevia-G/PVP could be maintained even after the preparation of jelly and release into a dissolution media. Production of jelly formulations using Stevia-G and PVP are a promising way to improve the dissolution properties of CUR. [ABSTRACT FROM AUTHOR]

Proniosomes (PN) are the dry water-soluble carrier systems that may enhance the oral bioavailability, stability, and topical permeability of therapeutic agents. The low solubility and low oral bioavailability due to extensive first pass metabolism make Pentazocine as an ideal candidate for oral and topical sustained release delivery. The present study was aimed to formulate the PNs by quick slurry method that are converted to niosomes (liquid dispersion) by hydration, and subsequently formulated to semisolid niosomal gel. The PNs were found in spherical shape in the SEM and stable in the physicochemical and thermal analysis (FTIR, TGA, and XRD). The quick slurry method produced high recovery (> 80% yield) and better flow properties (θ = 28.1-37.4°). After hydration, the niosomes exhibited desirable entrapment efficiency (44.45-76.23%), size (4.98-21.3 μm), and zeta potential (− 9.81 to − 21.53 mV). The in vitro drug release (T100%) was extended to more than three half-lives (2-4 h) and showed good fit to Fickian diffusion indicated by Korsmeyer-Peppas model (n = 0.136-0.365 and R2 = 0.9747-0.9954). The permeation of niosomal gel was significantly enhanced across rabbit skin compared to the pure drug-derived gel. Therefore, the PNs are found promising candidates for oral as dissolution enhancement and sustained release for oral and topical delivery of pentazocine for the management of cancer pain. [ABSTRACT FROM AUTHOR]

Glibenclamide (GB), oral antidiabetic sulfonylurea, is used in the management of diabetes mellitus type II. It suffers from low bioavailability due to low water solubility. This work aimed to enhance the dissolution of GB by formulating the drug as a proniosomes which then improves the pharmacological effect. GB proniosomal formulations were prepared using a slurry method with sucrose as a carrier. The formulations were characterized by particle size, zeta potential, entrapment efficiency %, flow properties of the powder, and in vitro dissolution study. The pharmacological effect was also assessed by determining and measuring the fasting blood glucose level (BGL) before and after the treatment. Formulating GB proniosomes with the slurry method produces a free-flowing powder with a particle size range from 190.050 ± 43.204 to 1369.333 ± 150.407 nm and the zeta potential was above 20 mV (-24 to −58 mV), indicating good stability. The dissolution rate for all formulations was higher than that of the pure drug, indicating the efficiency of the proniosome in enhancing the drug solubility. A significant reduction in the fasting blood glucose level (73 %) was observed in animals treated with proniosomal formulation with no sign of liver damage. In contrast, the pharmacodynamics results show a significant reduction in fasting blood glucose level for animals treated with proniosomes compared to a 17.6 % reduction in BGL after treatment with pure drug. Moreover, the histopathological results showed no sign of liver damage that occurred with proniosomal treatment. GB proniosomal formulations is a promising drug delivery system with good therapeutic efficacy and stability. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present investigation was preparation and characterization of sirolimus solid dispersions by solvent evaporation technique to improve its dissolution properties. Methods: Polyvinylpyrrolidone (PVP), Poloxamer 188 and Cremophore RH40 were used to prepare the solid dispersions of sirolimus. In vitro dissolution study using USP type I apparatus, were performed in distilled water (containing SLS 0.4%) for pure sirolimus, physical mixtures, Rapamune and prepared solid dispersions. The characterization of solid dispersions was performed using Fourier Transform Infrared (FTIR) Spectroscopy and Differential Scanning Calorimetry (DSC). Results: More than 75% of sirolimus was released within 30 minutes from all prepared solid dispersions. The dissolution rate of all prepared solid dispersion powders were more than physical mixtures. The absence of sirolimus peak in the DSC spectrum of solid dispersions indicated the conversion of crystalline form of sirolimus into amorphous form. The results from FT-IR spectroscopy showed that there was no significant change in the FT-IR spectrum of solid dispersions indicating absence of well-defined interaction between drug and carriers. Conclusion: It was concluded that solid dispersion method, using PVP, Poloxamer 188 and Cremophore RH40 can improve dissolution rate of sirolimus.

In order to improve the aqueous solubility and dissolution of Tacrolimus (TAC), amorphous solid dispersions of TAC were prepared by hot melt extrusion with three hydrophilic polymers, Polyvinylpyrrolidone vinyl acetate (PVPVA64), Soluplus® andHydroxypropylCellulose (HPC), at a drug loading of 10% w/w. Molecular modeling was used to determine the miscibility of the drug with the carrier polymers by calculating the Hansen Solubility Parameters. Powder X-ray diffraction and differential scanning calorimetry (DSC) studies of powdered solid dispersions revealed the conversion of crystalline TAC to amorphous form. Fourier transform Infrared (FTIR) spectroscopy results indicated formation of hydrogen bond between TAC and polymers leading to stabilization of TAC in amorphous form. The extrudates were found to be stable under accelerated storage conditions for 3 months with no re-crystallization, indicating that hot melt extrusion is suitable for producing stable amorphous solid dispersions of TAC in PVP VA64, Soluplus® and HPC. Stable solid dispersions of amorphous TAC exhibited higher dissolution rate, with the solid dispersions releasing more than 80% drug in 15 min compared to the crystalline drug giving 5% drug release in two hours. These stable solid dispersions were incorporated into orally-disintegrating tablets in which the solid dispersion retained its solubility, dissolution and stability advantage. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to use commercial available polymers like PVP/PEG, soluplus® and kollidon® SR to prepare immediate and sustained release formulations of felodipine by hot melt mixing method. Solid dispersions containing 5, 10, 20 and 30 wt% drug have been prepared in a Haake-Buchler Reomixer at melt temperature 130 °C and mixing time 10 min. As was found from DSC and XDR studies completely amorphous and miscible solid dispersions can be prepared. In all cases a single glass transition was recorded, which is depended from the used drug amount. Hydrogen bonds and the molecular interaction between felodipine and polymer matrices are responsible for the miscibility of prepared formulations. This has as result the substantial enhancement of felodipine release rate in PVP/PEG mixture and due to the high solubility of used polymers immediate release formulations have been prepared. On the contrary, sustained release formulations can be prepared in the case of kollidon SR solid dispersions. The release mechanism of all preparations was studied using different kinetic models. Finally, binding affinity values calculated by molecular docking simulations were used as estimators for predicting long-term drug's physical stability in solid dispersions. [ABSTRACT FROM AUTHOR]

Boswellic acids (BAs) are a group of pentacyclic triterpenes present in gum-resin of Boswellia serrata . They are well known for their anti-inflammatory, hypolipidemic, immunomodulatory and anti-tumor activity, but they have poor aqueous solubility and limited bioavailability. In order to enhance their aqueous solubility, inclusion complexes of BAs with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) were synthesized and their drug release profiles were studied. Molecular associations of β-CD and HP-β-CD with BAs were investigated by phase solubility studies. The stability constants were found to be 380.2 and 145.9 M -1 for BA: β-CD and BA: HP-β-CD inclusion complexes, respectively with A N - type curve. BA: β-CD and BA: HP-β-CD inclusion complexes were synthesized using kneading (KN), co-precipitation (CP) and solvent evaporation (SE) methods in 1:1 as well as 1:2 ratios. Further these were characterized by Fourier transform infrared (FTIR) spectrophotometry, Powder X-ray Diffraction (P-XRD) and Differential scanning calorimetric (DSC) analysis. FTIR analysis showed shifting of frequencies in complexes as compared to CDs and BAs. P-XRD data obtained for BA: β-CD complexes synthesized by CP and SE methods showed amorphous pattern. Also, DSC analysis showed a change in thermal behaviour for synthesized complexes. In vitro drug release studies of BA: β-CD complexes showed enhanced release with 1:2 complexes than 1:1 complexes at pH 1.2 and pH 6.8. Similarly, drug release enhancement was observed more with BA: HP-β-CD complexes in 1:2 ratio than 1:1. To understand the interaction of BAs with CD cavity molecular modelling studies were performed which favored 1:2 complex formation over 1:1 complexes. The study thus highlights that CDs can be used for solubility and dissolution enhancement of BAs. [ABSTRACT FROM AUTHOR]

The present study demonstrated the binary and ternary complexes of Zaltoprofen (ZPF) with β-CD and HP-β-CD. The products were characterized using solubility, in vitro dissolution, and DSC studies. The mode of interaction of guest and host was revealed through 1 H NMR and FT-IR studies. A significant increase was noticed in the stability constant (K c ) and complexation efficiency (CE) of β-CD and HP-β-CD due to addition of L-Arg in ternary complexes. The ternary complexes showed greater increase in solubility and dissolution of ZPF than binary complexes. Thus, ternary system of ZPF could be an innovative approach for its solubility and dissolution enhancement. [ABSTRACT FROM AUTHOR]

Raloxifene HCl (RLX) is a BCS class - II drug, used in osteoporosis. For RLX liquisolid compacts (LSC), selection of non volatile liquid vehicle, carrier, coating material, super disintegrant were done and they were developed by using Propylene Glycol (PG): Polyethylene Glycol (PEG) 600 as a combination of non volatile liquid vehicles, Avicel PH101 as a carrier, Aeroperl 300 as coating material and Kyron T 314 as super disintegrant. The optimized batch was characterized by tests like flow property, content uniformity of mass, weight variation, tablet hardness, friability, disintegration time, XRD (X-ray diffraction) study, in vitro drug release test. The results of in vitro drug release study of RLX optimized batch illustrated a remarkable improvement in the dissolution rate as compared to Reference product (Ralista) and pure drug with other parameters of tablet. Accelerated stability study of the optimized batch was done for 3 months (at 25°C ± 2°C temperature and 40% ± 5% Relative humidity) and showed no significant change in appearance, drug content and in vitro drug release. This study concluded that LSC of RLX prove as one of the suitable approach for developing stable solid oral dosage form of poorly water soluble drug - RLX. [ABSTRACT FROM AUTHOR]

A promising approach to increase the aqueous solubility, hence the bioavailability, of poorly water-soluble drugs is to convert them into their amorphous state through impregnation into mesoporous silica. Unfortunately, mesoporous silica is not yet available in bulk quantities due to high manufacturing costs. In this work, feasibility of using a commercially available cost-effective mesoporous fine grade Neusilin ® UFL2 to prepare amorphous drug composites of 2 model poorly soluble drugs, fenofibrate and itraconazole, is established. In contrast to fluidized-bed spray-impregnation, only mixing and drying steps are required. Complimentary assessment using X-ray powder diffraction, differential scanning calorimetry, and Raman spectroscopy confirmed drug within the composites to be amorphous at as high as 30% drug loading both after formation and after 3 months of storage at 40°C and 75% relative humidity. Amorphous drug recrystallization was completely suppressed due to the confinement effect due to the Neusilin ® . The amorphous drug composites resulted in higher apparent solubility and faster dissolution rate of the model drugs as compared to their crystalline counterpart, confirmed by United States Pharmacopeia II dissolution and ultraviolet surface dissolution imaging. Overall, stable, high drug-loaded fast-dissolving amorphous drug composites preparation using Neusilin ® UFL2 is demonstrated as a promising approach to enhance solubility of poorly soluble drugs. [ABSTRACT FROM AUTHOR]

New approaches in pharmaceutical chemistry have resulted in more complex drug molecules in the quest to achieve higher affinity to their targets. However, these ‘highly active’ drugs can also suffer from poor water solubility. Hence, poorly water soluble drugs became a major challenge in drug formulation, and this problem is increasing, as currently about 40 of the marketed drugs and 90% of drug candidates are classified as poorly water soluble. Various approaches exist to circumvent poor water solubility and poor dissolution rate in aqueous environment, however, each having disadvantages and certain limitations. Recently, mesoporous silica materials (MSMs) have been proposed to be used as matrices for enhancing the apparent solubility and dissolution rate of different drug molecules. MSMs are ideal candidates for this purpose, as silica is a “generally regarded as safe” (GRAS) material, is biodegradable, and can be readily surface-modified in order to optimize drug loading and subsequent release in the human body. The major advantage of mesoporous silica as drug delivery systems (DDSs) for poorly water soluble drugs lies in their pore size, pore morphology, and versatility in alteration of the surface groups, which can result in optimized interactions between a drug candidate and MSM carrier by modifying the pore surfaces. Furthermore, the drug of interest can be loaded into these pores in a preferably amorphous state, which can increase the drug dissolution properties dramatically. The highlights of this review include a critical discussion about the modification of the physico-chemical properties of MSMs and how these physico-chemical modifications influence the drug loading and the subsequent dissolution of poorly water soluble drugs. It aims to further promote the use of MSMs as alternative strategy to common methods like solubility enhancement by cyclodextrins, micronization, or microemulsion techniques. This review can provide guidance on how to tailor MSMs to achieve optimized drug loading and drug dissolution. [ABSTRACT FROM AUTHOR]

Nanocrystals of tadalafil, a poorly water-soluble drug, were successfully prepared by sonoprecipitation technique for improving the solubility and dissolution rate. Tween 80 was selected as an efficient surfactant to inhibit aggregation in stabilization of drug nanocrystals. Response surface methodology based on central composite design (CCD) was utilized to evaluate the formulation factors affecting the size of nanosuspensions. Under optimum conditions, relatively spherical nanocrystals with a mean particle size of 358.47 ± 11.95 nm were obtained. FTIR analysis indicated that the precipitated nanoparticles had the same chemical structure as the raw tadalafil. By DSC analysis, no substantial crystalline change was found in the nanocrystals compared with the unprocessed drug. In addition, the dissolution rate of the processed tadalafil nanocrystals in 120 min was significantly increased (3.61-fold) as compared to that of the raw material. Therefore, it was concluded that the sonoprecipitation technique could be a simple and useful technique to prepare poorly water-soluble drug particles with reduction in particle size, a narrow particle size distribution and enhanced dissolution properties. [ABSTRACT FROM AUTHOR]

LASSBio-294 (3,4-methylenedioxybenzoyl-2-thienylhydrazon) is a poorly soluble drug which has been proposed to have major advantages over other cardiotonic drugs. Poorly water soluble drugs present limited bioavailability due to their low solubility and dissolution rate. An antisolvent crystallization processing can improve the dissolution rate by decreasing the crystals particle size. However, LASSBio-294 is also poorly soluble in organic solvents and this operation is limited. In order to open new perspectives to improve dissolution rate, this work has investigated LASSBio-294 in terms of its antisolvent crystallization in 1-ethyl-3-methylimidazolium methyl phosphonate [emim][CH 3 O(H)PO 2 ] as solvent and water as antisolvent. Two modes of mixing are tested in stirred vessel with different pre-mixers (Roughton or T-mixers) in order to investigate the mixing effect on the crystal properties (crystalline structure, particle size distribution, residual solvent and in vitro dissolution rate). Smaller drug particles with unchanged crystalline structure were obtained. Despite the decrease of the elementary particles size, the recrystallized particles did not achieve a better dissolution profile. However, this study was able to highlight a certain number of findings such as the impact of the hydrodynamic conditions on the crystals formation and the presence of a gel phase limiting the dissolution rate. [ABSTRACT FROM AUTHOR]