Co-Processed Crystalline Solids of Ivermectin with Span® 60 as Solubility Enhancers of Ivermectin in Natural Oils.

Despite being discovered over five decades ago, little is still known about ivermectin. Ivermectin has several physico-chemical properties that can result in it having poor bioavailability. In this study, polymorphic and co-crystal screening was used to see if such solid-state modifications can improve the oil solubility of ivermectin. Span® 60, a lipophilic non-ionic surfactant, was chosen as co-former. The rationale behind attempting to improve oil solubility was to use ivermectin in future topical and transdermal preparations to treat a range of skin conditions like scabies and head lice. Physical mixtures were also prepared in the same molar ratios as the co-crystal candidates, to serve as controls. Solid-state characterization was performed using X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The FTIR spectra of the co-crystal candidates showed the presence of Span® 60's alkyl chain peaks, which were absent in the spectra of the physical mixtures. Due to the absence of single-crystal X-ray data, co-crystal formation could not be confirmed, and therefore these co-crystal candidates were referred to as co-processed crystalline solids. Following characterization, the solid-state forms, physical mixtures and ivermectin raw material were dissolved in natural penetration enhancers, i.e., avocado oil (AVO) and evening primrose oil (EPO). The co-processed solids showed increased oil solubility by up to 169% compared to ivermectin raw material. The results suggest that co-processing of ivermectin with Span® 60 can be used to increase its oil solubility and can be useful in the development of oil-based drug formulations.

Investigation and Evaluation of the Transdermal Delivery of Ibuprofen in Various Characterized Nano-Drug Delivery Systems.

The aim was to assess the suitability of three nano-based transdermal drug delivery systems containing ibuprofen: a nano-emulsion, a nano-emulgel, and a colloidal suspension with ibuprofen-loaded nanoparticles. Understanding the transdermal delivery of ibuprofen using nano-based drug delivery systems can lead to more effective pain relief and improved patient compliance. Characterization tests assessed the suitability of the developed drug delivery systems. Membrane release and skin diffusion studies, along with tape stripping, were performed to determine drug release and skin permeation of ibuprofen. In vitro cytotoxicity studies on HaCaT cells were conducted using MTT and neutral red assays to evaluate the safety of the developed drug delivery systems. Characterization studies confirmed stable drug delivery systems with ideal properties for transdermal delivery. Membrane release studies demonstrated the successful release of ibuprofen. In vitro skin diffusion experiments and tape stripping, detecting ibuprofen in the receptor phase, stratum corneum-epidermis, and epidermis-dermis, indicating successful transdermal and topical delivery. The in vitro cytotoxicity studies observed only minor cytotoxic effects on HaCaT cells, indicating the safety of the developed drug delivery systems. The investigation demonstrated promising results for the transdermal delivery of ibuprofen using the developed drug delivery systems, which contributes to valuable insights that may lead to improved pain management strategies.

Comparative study on the topical and transdermal delivery of diclofenac incorporated in nano-emulsions, nano-emulgels, and a colloidal suspension.

Transdermal delivery of active pharmaceutical ingredients (APIs) can be challenging, since the skin possesses a rate-limiting barrier, which may be overcome when APIs possess certain ideal physicochemical properties. The lack thereof would require that APIs be included in drug delivery vehicles to enhance skin permeation. Hence, diclofenac was incorporated into various drug delivery vehicles (i.e., nano-emulsions, nano-emulgels, and a colloidal suspension containing drug-loaded nanoparticles) to investigate the transdermal delivery thereof, while nano-emulsions and nano-emulgels had varying concentrations of evening primrose oil (EPO). The aim of the study was to compare the topical and transdermal diclofenac delivery from the different types of vehicles and to investigate the influence the different EPO concentrations had on diclofenac delivery. After characterization, membrane release studies were performed (to determine whether the API was successfully released from the vehicle) followed by in vitro skin diffusion studies and tape stripping (to establish whether the vehicles assisted the API in reaching the target site (transdermal delivery)). Lastly, cytotoxicity studies were conducted via methyl thiazolyl tetrazolium (MTT) and neutral red (NR) assays on human keratinocyte (HaCaT) cells. Results showed minimal cytotoxic effects at concentrations equivalent to that which had permeated through the skin, while the membrane release and in vitro skin diffusion studies indicated that the nano-emulsions and the 10% EPO vehicles increased API release and diffusion when compared to the other vehicles. However, the colloidal suspension had the highest concentrations of API within the skin. Hence, all the vehicles were non-toxic and effectively delivered diclofenac through the transdermal route.

Optimal 10-Aminoartemisinins With Potent Transmission-Blocking Capabilities for New Artemisinin Combination Therapies-Activities Against Blood Stage P. falciparum Including PfKI3 C580Y Mutants and Liver Stage P. berghei Parasites.

We have demonstrated previously that amino-artemisinins including artemiside and artemisone in which an amino group replaces the oxygen-bearing substituents attached to C-10 of the current clinical artemisinin derivatives dihydroartemisinin (DHA), artemether and artesunate, display potent activities in vitro against the asexual blood stages of Plasmodium falciparum (Pf). In particular, the compounds are active against late blood stage Pf gametocytes, and are strongly synergistic in combination with the redox active drug methylene blue. In order to fortify the eventual selection of optimum amino-artemisinins for development into new triple combination therapies also active against artemisinin-resistant Pf mutants, we have prepared new amino-artemisinins based on the easily accessible and inexpensive DHA-piperazine. The latter was converted into alkyl- and aryl sulfonamides, ureas and amides. These derivatives were screened together with the comparator drugs DHA and the hitherto most active amino-artemisinins artemiside and artemisone against asexual and sexual blood stages of Pf and liver stage P. berghei (Pb) sporozoites. Several of the new amino-artemisinins bearing aryl-urea and -amide groups are potently active against both asexual, and late blood stage gametocytes (IC50 0.4-1.0 nM). Although the activities are superior to those of artemiside (IC50 1.5 nM) and artemisone (IC50 42.4 nM), the latter are more active against the liver stage Pb sporozoites (IC50 artemisone 28 nM). In addition, early results indicate these compounds tend not to display reduced susceptibility against parasites bearing the Pf Kelch 13 propeller domain C580Y mutation characteristic of artemisinin-resistant Pf. Thus, the advent of the amino-artemisinins including artemiside and artemisone will enable the development of new combination therapies that by virtue of the amino-artemisinin component itself will possess intrinsic transmission-blocking capabilities and may be effective against artemisinin resistant falciparum malaria.

Phenolic and physicochemical stability of a functional beverage powder mixture during storage: effect of the microencapsulant inulin and food ingredients.

BACKGROUND: The need for a convenience herbal iced tea product with reduced kilojoules merited investigation of the shelf-life of powder mixtures containing a green Cyclopia subternata Vogel (honeybush) extract with proven blood glucose-lowering activity and alternative sweetener mixture. RESULTS: Prior to long-term storage testing, the wettability of powder mixtures containing food ingredients and the compatibility of their components were confirmed using the static sessile drop method and isothermal microcalorimetry, respectively. The powders packed in semi-sealed containers remained stable during storage at 25 °C/60% relative humidity (RH) for 6 months, except for small losses of specific phenolic compounds, namely mangiferin, isomangiferin, 3-ß-d-glucopyranosyliriflophenone, vicenin-2 and 3',5'-di-ß-d-glucopyranosylphloretin, especially when both citric acid and ascorbic acid were present. These acids drastically increased the degradation of phenolic compounds under accelerated storage conditions (40 °C/75% RH). Accelerated storage also caused changes in the appearance of powders and the colour of the reconstituted beverage solutions. Increased moisture content and aw of the powders, as well as moisture released due to dehydration of citric acid monohydrate, contributed to these changes. CONCLUSION: A low-kilojoule honeybush iced tea powder mixture will retain its functional phenolic compounds and physicochemical properties during shelf-life storage at 25 °C for 6 months. © 2017 Society of Chemical Industry.

Amorphous Sulfadoxine: A Physical Stability and Crystallization Kinetics Study.

Poor aqueous solubility of drugs and the improvement thereof has always been a challenge for the pharmaceutical industry. With this, one of the focuses of the pharmaceutical research scientist involves investigating possible metastable forms of a given drug to be incorporated into solid dosage forms. The rationale being, the improved solubility offered by the metastable solid-state forms of drugs. Solubility remains a major challenge for formulation scientists, especially with antimicrobial agents where the emergence of resistance is directly dependent on the concentration and duration of the parasite exposed to the drug. Sulfadoxine-pyrimethamine combination therapies are still the recommended treatments for uncomplicated Plasmodium falciparum malaria. The aim of this study was to prepare an amorphous form of sulfadoxine and to investigate the stability and recrystallization behavior thereof. The amorphous form was prepared by the well-known quench cooling of the melt. The physico-chemical properties and stability of amorphous sulfadoxine were studied using hot-stage microscopy (HSM), scanning electron microscopy (SEM), x-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), as well as microcalorimetry. The recrystallization kinetics were studied isothermally by applying the Johnson-Mehl-Avrami model and non-isothermally by applying the Kissinger model. The physical stabilization of the amorphous form was investigated using physical mixtures of amorphous sulfadoxine with polyvinylpyrrolidone-25 (PVP-25). It was proved that sulfadoxine is a good glass former with relative high physical stability; however, water acts as a strong plasticizer for amorphous sulfadoxine, detrimentally affecting the stability during exposure to high moisture conditions.

Different amorphous solid-state forms of roxithromycin: A thermodynamic and morphological study.

The striking impact that different preparation methods have on the characteristics of amorphous solid-state forms has attracted considerable attention during the last two decades. The pursuit of more extensive knowledge regarding polyamorphism therefore continues. The aim of this study was firstly, to investigate the influence of different preparation techniques to obtain amorphous solid-state forms for the same active pharmaceutical ingredient, namely roxithromycin. The preparation techniques also report on a method utilizing hot air, which although it is based on a melt intermediary step, is considered a novel preparation method. Secondly, to conduct an in-depth investigation into any physico-chemical differences between the resulting amorphous forms and thirdly, to bring our findings into context with that of previous work done, whilst simultaneously discussing a well-defined interpretation for the term polyamorphism and propose a discernment between true polyamorphism and pseudo-polyamorphism/atypical-polyamorphism. The preparation techniques included melt, solution, and a combination of solution-mechanical disruption as intermediary steps. The resulting amorphous forms were investigated using differential scanning calorimetry, X-ray powder diffraction, hot-stage microscopy, scanning electron microscopy, and vapor sorption. Clear and significant thermodynamic differences were determined between the four amorphous forms. It was also deduced from this study that different preparation techniques have a mentionable impact on the morphological properties of the resulting amorphous roxithromycin powders. Thermodynamic properties as well as the physical characteristics of the amorphous forms greatly governed other physico-chemical properties i.e. solubility and dissolution.

The Stabilization of Amorphous Zopiclone in an Amorphous Solid Dispersion.

Zopiclone is a poorly soluble psychotherapeutic agent. The aim of this study was to prepare and characterize an amorphous form of zopiclone as well as the characterization and performance of a stable amorphous solid dispersion. The amorphous form was prepared by the well-known method of quench-cooling of the melt. The solid dispersion was prepared by a solvent evaporation method of zopiclone, polyvinylpyrrolidone-25 (PVP-25), and methanol, followed by freeze-drying. The physico-chemical properties and stability of amorphous zopiclone and the solid dispersion was studied using differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), hot-stage microscopy (HSM), X-ray diffractometry (XRD), solubility, and dissolution studies. The zopiclone amorphous solid-state form was determined to be a fragile glass; it was concluded that the stability of the amorphous form is influenced by both temperature and water. Exposure of amorphous zopiclone to moisture results in rapid transformation of the amorphous form to the crystalline dihydrated form. In comparison, the amorphous solid dispersion proved to be more stable with increased aqueous solubility.

Amorphous azithromycin with improved aqueous solubility and intestinal membrane permeability.

Azithromycin (AZM) is a poorly soluble macrolide antibacterial agent. Its low solubility is considered as the major contributing factor to its relatively low oral bioavailability. The aim of this study was to improve the solubility of this active pharmaceutical ingredient (API) by preparing an amorphous form by quench cooling of the melt and to study the influence of the improved solubility on membrane permeability. The amorphous azithromycin (AZM-A) exhibited a significant increase in water solubility when compared to the crystalline azithromycin dihydrate (AZM-DH). The influence that the improved solubility could have on membrane permeability was also studied. The apparent permeability coefficient (Papp) values of AZM-A were statistically significantly higher (p < 0.05) than crystalline AZM-DH at pH values of 6.8 and 7.2. The results therefore indicated that the improved solubility of AZM in the amorphous form also produced improved permeability across excised intestinal tissue at physiological pH values found in the small intestine.

Solution-mediated phase transformation of different roxithromycin solid-state forms: Implications on dissolution and solubility.

The objective of this study was to describe the solid-state forms in which roxithromycin may exist and the significant influence of solution-mediated phase transformation on the dissolution and solubility behavior of these forms. Roxithromycin may exist as: Form I (monohydrate), Form II (amorphous), Form III (anhydrate) and a mixture of Forms I and III. Form III and Mixture I/III have not been reported previously, probably due to incomplete solid-state characterization or the use of a standard production method which consistently yielded the same solid-state form. Solution-mediated phase transformations of Forms II and III to the stable Form I were proved through dissolution studies and quantification of the phase proportions, as a function of time, utilizing XRPD. This study showed that pharmacopoeial identification methods for roxithromycin do not allow accurate identification of the different solid-state forms. The various forms differed significantly in terms of dissolution profiles, which could have a marked influence on bioavailability and performance of the final dosage form. It was demonstrated that solvent replacement, during dissolution testing, masks the characteristic profile usually obtained with a metastable form undergoing solution-mediated transformation. Finally, we propose that peak dissolution concentrations should be used to give a more exact indication of the aqueous solubility enhancement ratio obtained with metastable forms of APIs.

Poly(amidoamine) dendrimer-mediated synthesis and stabilization of silver sulfonamide nanoparticles with increased antibacterial activity.

Silver sulfadiazine (AgSD) is a topical antibiotic with limited aqueous solubility. In this study, it was shown that poly(amido amine) (PAMAM) dendrimer complexes with SD (SDZ) and silver (Ag) could be used for a bottom-up approach to synthesize highly-soluble AgSD nanoparticles (NPs). These NPs were stabilized against crystal growth by electrostatic layer-by-layer (LBL) coating with various PAMAM dendrimers. Additionally, AgNPs can be incorporated in the dendrimer shells that augmented AgSD release. NP formulation in a cream base provided a topical drug-delivery platform with enhanced antibacterial properties against burn-wound infections, comprising three nanostructures i.e., nano-AgSD, AgNPs as well as PAMAM dendrimers, in one efficient, elegant nanosystem. FROM THE CLINICAL EDITOR: In this paper an elegant silver sulfadiazine-based nanoparticle complex is demonstrated with enhanced antibacterial properties and improved solubility for the treatment of burn-wound infections in a topical crème formulation.

Physicochemical properties of amorphous roxithromycin prepared by quench cooling of the melt or desolvation of a chloroform solvate.

Roxithromycin is a poorly soluble antibacterial drug. The aim of this study was to prepare and characterize an amorphous form of roxithromycin. The amorphous form was prepared by desolvation of its chloroform solvate, and by quench cooling a melt of the crystalline monohydrated solid. The X-ray powder diffraction pattern of the desolvated chloroform solvate was indistinguishable from that of the glass prepared by melting, which indicated that it was amorphous. The roxithromycin glass was determined to be a fragile glass, but due to its high Kauzmann temperature (approximately 8°C), it should remain fairly stable upon refrigeration or even at room temperature. It was also determined that this glass remains stable in the presence of moisture with no indication of crystallization.

Crystallization of toxic glycol solvates of rifampin from glycerin and propylene glycol contaminated with ethylene glycol or diethylene glycol.

This study was initiated when it was suspected that syringe blockage experienced upon administration of a compounded rifampin suspension was caused by the recrystallization of toxic glycol solvates of the drug. Single crystal X-ray structure analysis, powder X-ray diffraction, thermal analysis and gas chromatography were used to identify the ethylene glycol in the solvate crystals recovered from the suspension. Controlled crystallization and solubility studies were used to determine the ease with which toxic glycol solvates crystallized from glycerin and propylene glycol contaminated with either ethylene or diethylene glycol. The single crystal structures of two distinct ethylene glycol solvates of rifampin were solved while thermal analysis, GC analysis and solubility studies confirmed that diethylene glycol solvates of the drug also crystallized. Controlled crystallization studies showed that crystallization of the rifampin solvates from glycerin and propylene glycol depended on the level of contamination and changes in the solubility of the drug in the contaminated solvents. Although the exact source of the ethylene glycol found in the compounded rifampin suspension is not known, the results of this study show how important it is to ensure that the drug and excipients comply with pharmacopeial or FDA standards.

Preparation and transformation of true nifedipine polymorphs: investigated with differential scanning calorimetry and X-Ray diffraction pattern fitting methods.

The amorphous → metastable and metastable → stable crystalline phase transitions of nifedipine and their relationship with polymorph composition during storage at controlled temperature/humidity conditions were investigated. Metastable form C was produced from both differential scanning calorimetry (DSC) thermal treatment and storage [22 °C/0% and 75% relative humidity (RH)] of the amorphous form. Amorphous conversion rate accelerated with storage temperature up to 40 °C, but a further 8 °C increase to 48 °C (3 °C above the glass transition) resulted in a more than 12-fold decrease in amorphous conversion rate. DSC and X-Ray diffraction (XRD) analysis revealed a faster amorphous conversion rate relative to the metastable crystal transformation with 75% RH having a greater accelerative effect on the former. Relative phase quantification from XRD pattern fitting included the use of integrated peak intensities of the crystalline phases, Rietveld and the Rietveld-based partial or no known crystal structures method. Kinetic analysis with Johnson-Mehl-Avrami equation indicated that the accelerated amorphous conversion in 75% RH was associated with a 10-fold increase in rate constant with dimensional growth little affected. The smaller rate increase for metastable crystal conversion was associated with an increased dimensional growth while the rate constant was little affected.

Preparation and characterization of directly compactible layer-by-layer nanocoated cellulose.

Microcrystalline cellulose is a commonly used direct compression tablet diluent and binder. It is derived from purified α-cellulose in an environmentally unfriendly process that involves mineral acid catalysed hydrolysis. In this study Kraft softwood fibers was nanocoated using a layer-by-layer self-assembling process. Powder flow and compactibility results showed that the application of nano-thin polymer layers on the fibers turned non-flowing, non-compacting cellulose into powders that can be used in the direct compression of tablets. The powder flow properties and tableting indices of compacts compressed from these nanocoated microfibers were similar or better than that of directly compactible microcrystalline cellulose powders. Cellulose microfibers coated with four PSS/PVP bilayers had the best compaction properties while still producing tablets that were able to absorb water and disintegrate and did not retard the dissolution of a model drug acetaminophen. The advantages of nanocoating rather than traditional pharmaceutical coating are that it add less than 1% to the weight of the fibers and allows control of the molecular properties of the surface and the thickness of the coat to within a few nanometers. This process is potentially friendlier to the environment because of the type and quantity of materials used. Also, it does not involve acid-catalyzed hydrolysis and neutralization of depolymerized cellulose.

Characterization of polymorph transformations that decrease the stability of tablets containing the WHO essential drug mebendazole.

This study investigated the influence of moisture and heat on the stability of mebendazole polymorph C in tablets. The polymorphic forms of mebendazole display significant differences in solubility and therapeutic efficacy and form C is preferred clinically due to its optimal bioavailability and reduced toxicity. An accelerated stability study of the polymorphs revealed that the Johnson-Mehl-Avrami-Erofeyev-Kolmogorov (JMAEK) model best described the kinetics of the solid-state transformation of form C to A. Rate constants obtained using this model was used to calculated half-lives and shelf lives of products stored under ICH conditions of 30 degrees C + 65% RH and 40 degrees C + 75% RH. Results showed that form C was converted to the thermodynamic stable, least soluble form A with increased temperatures and moisture, and at constant temperature and relative humidity this transformation was significantly increased when trace amounts of form A was present in the tablets. Four out of the seven products tested contained trace amounts of form A. In some tablets, the transformation to form A was so quick that it reduced the shelf life to less than 1 month. The tablet dissolution of these products was reduced to such an extent that it did not comply with USP and FDA specifications.

The effect of temperature and moisture on the amorphous-to-crystalline transformation of stavudine.

Stavudine is a nucleoside reverse transcriptase inhibitor active against HIV, and is known to exist in two polymorphic forms designated as forms I and II, and a hydrate form III. An amorphous solid of stavudine was successfully prepared and characterized during this investigation. A comprehensive evaluation of the stability of this amorphous solid showed that the amorphous solid transforms to either form II (anhydrous) or form III (hydrate) when exposed to temperature, in the absence or presence of moisture, respectively. The amorphous-to-hydrate transformation occurred at relatively low RH (>32%) and led to the formation of crystal aggregates of the hydrated form. Steady state growth rate analyses also showed that the amorphous-to-crystalline transformation occurs at a greater rate in the presence of moisture, compared to the transformation at the same temperature in a dry environment. Crystal growth studies showed that it is possible to stabilize the amorphous solid of stavudine against crystal transformations in the absence of moisture by coating it with poly(methyl methacrylate). However, this polymer coating could not prevent crystal growth from the amorphous solid during exposure to moisture.

Effect of para-sulfonato-calix[n]arenes on the solubility, chemical stability, and bioavailability of a water insoluble drug nifedipine.

This study reports the use of para-sulphonato calix[8]arene to produce stable complexes with improved bioavailability for nifedipine, a calcium-channel blocker that is practically insoluble in water. Thermal analysis and electrospray ionisation mass spectroscopy confirmed that nifedipine formed complexes with the calixarenes in a size dependent way. The most stable, soluble complexes was formed with para-sulphonato calix[8]arene. Complexation was weakest with the calix[4]arene while complexation with the calix[6]arene was intermediate. However, the calix[4 and 6]arenes changed the chemical stability of the drug in solution because significant amounts of the nitroso-pyridine derivative was produced, proposing an interaction between the nifedipine bearing a H substituent at the N-1 position and the calixarenes. This oxidative degradation of the drug was greatest when combined with the calix[6]arene. Simultaneous oral ingestion of the calix[6 or 8]arenes significantly increased the bioavailability of the drug after oral administration in male Sprague-Dawley rats while not influencing CYP3A activities in the liver. The pharmacokinetic parameters of the nifedipine: para-sulfonato calix[8]arene complexes showed it was bioequivalent to a nifedipine PEG-solution. The absolute bioavailability for both formulations was ca. 60 %.

Development of microporous drug-releasing films cast from artificial nanosized latexes of poly(styrene-co-methyl methacrylate) or poly(styrene-co-ethyl methacrylate).

Two sets of copolymers comprising of styrene and either methyl or ethyl methacrylate as comonomer were conveniently synthesized by microemulsion copolymerization. The purified materials were characterized by GPC-MALLS and were shown to form artificial nanolatexes in THF. ATR-FTIR analysis revealed differences in copolymer composition and based on the copolymer properties, a selection of copolymers was chosen to cast drug-loaded, microporous films that exhibit microencapsulation of drug agglomerates. The contact angles of the copolymers suggested potential applications in medical devices to prevent the formation of bacterial biofilms that commonly result in infections. Additionally, the different copolymeric films showed two phases of drug release characterized by a rapid initial drug release followed by a zero-order phase. Depending on the application, one could select the copolymer films that best suited the application i.e. for short-term drug release applications such as urinary catheters or long-term applications such as artificial implants.

Nanoparticle multilayers: surface modification of photosensitive drug microparticles for increased stability and in vitro bioavailability.

The results of this study report the novel use of electrostatic layer-by-layer nanoassembly of biocompatible nanoparticulate TiO2 multilayers to coat irregular nifedipine (NF) microcrystals to increase the photostability of the drug when exposed to simulated sunlight and to increase the dissolution rate and possibly the bioavailability of the drug after oral administration. The photostability of NF microcrystals (35 microm) coated with multiple bilayers of positively charged PDDA and negatively charged nanosized TiO2 particles (20-25 nm) was measured when exposed to an illuminance of 12 W/m2 corresponding to a light dose of 30 k lux or 25 W/m2 corresponding to light dose of 60 k lux. The dissolution rate of nifedipine from the coated microcrystals was measured in simulated gastric fluid containing 0.05% w/v polysorbate 80. Coating with one TiO2 layer increased the shelf life of nifedipine by 30 hours independent of the intensity of the light exposure. With an increase in the number of TiO2 layers; the photostability of the drug was enhanced even more. A TiO2 monolayer decreased the contact angle by 20 degrees for water and 33 degrees for the dissolution medium as compared with uncoated NF surfaces. This increase in wettability due to a decrease in contact angle increased the dissolution rate of nifedipine microcrystals coated with 1 PDDA/TiO2 bilayer 13-fold after 10 minutes, 5-fold after 1 hour, and 2-fold after 12 hours when compared to uncoated microcrystals. It is assumed that TiO2 increased the photostability because the nanoparticulate multilayers acts as a potential filter protecting the drug from damaging light rays reaching the drug crystals. The dissolution rate was increased because the hydrophilic TiO2 nanoparticles increased the aqueous wettability of the drug crystals thereby preventing aggregation in the dissolution medium. This ensured that the maximum drug surface area was exposed to the dissolution medium.