Effect of N-trimethyl chitosan enhancing the dissolution properties of the lipophilic drug cyclosporin A

The aim was to evaluate the influence of N-trimethyl chitosan chloride (TMC) as a carrier for solid dispersion on the dissolution of poorly water-soluble drugs. In this study, we used cyclosporin A(CyA) as a model drug and TMC as a carrier. The effect of various formulation and process variables including TMC-to-CyA mixing weight ratio, weigh molecular(M_w) of TMC and methods used to disperse CyA along with the TMC on the drug dissolution was investigated. The nature of CyA dispersed in the matrix was studied by powder X-ray diffractometry (PXRD), diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and dissolution rate analyses. It was proved that all solid mixtures of CyA with TMCs showed a significantly rapid dissolution rate compared to pure drug and physical mixture. The greater the TMC content the higher the drug dissolution was, up to a maximum corresponding to a polymer: drug ratio of 3:1. The lower the M_w of TMC, the more important the polymer effect was. The dissolution of CyA was remarkably improved by the solid dispersion. The drug dissolution enhancement was attributed to the decreased drug crystallinity and size and polymer wetting effect. There was no significant difference in the efficiency of improving the drug dissolution between the solid dispersions prepared by solvent dispersing and by co-grinding. It was suggested that the TMC with a lower molecular weight is a useful carrier for solid dispersion.     

Development of prednisone: Polyethylene glycol 6000 fast-release tablets from solid dispersions: Solid-state characterization, dissolution behavior, and formulation parameters

The aim of the current study was to design oral fast-release polymeric tablets of prednisone and to optimize the drug dissolution profile by modifying the carrier concentration. Solid dispersions were prepared by the solvent evaporation method at different drug:polymer ratios (wt/wt). The physical state and drug:carrier interactions were analyzed by X-ray diffraction, infrared spectroscopy, and scanning electron microscopy. The dissolution rate of prednisone from solid dispersions was markedly enhanced by increasing the polymer concentration. The tablets were prepared from solid dispersion systems using polyethylene glycol (PEG) 6000 as a carrier at low and high concentration. The results showed that PEG 6000-based tablets exhibited a significantly higher prednisone dissolution (80% within 30 minutes) than did conventional tablets prepared without PEG 6000 (<25% within 30 minutes). In addition, the good disintegration and very good dissolution performance of the developed tablets without the addition of superdisintegrant highlighted the suitability of these formulated dosage forms. The stability studies performed in normal and accelerated conditions during 12 months showed that prednisone exhibited high stability in PEG 6000 solid dispersion powders and tablets. The X-ray diffraction showed that the degree of crystallinity of prednisone in solid dispersions decreased when the ratio of the polymer increased, suggesting that the drug is present inside the samples in different physical states. The Fourier transform infrared spectroscopic studies showed the stability of prednisone and the absence of well-defined drug:polymer interactions. Scanning electron microscopy images showed a novel morphology of the dispersed systems in comparison with the pure components.     

Thermal Processing of PVP- and HPMC-Based Amorphous Solid Dispersions

Thermal processing technologies continue to gain interest in pharmaceutical manufacturing. However, the types and grades of polymers that can be utilized in common thermal processing technologies, such as hot-melt extrusion (HME), are often limited by thermal or rheological factors. The objectives of the present study were to compare and contrast two thermal processing methods, HME and KinetiSol® Dispersing (KSD), and investigate the influence of polymer type, polymer molecular weight, and drug loading on the ability to produce amorphous solid dispersions (ASDs) containing the model compound griseofulvin (GRIS). Dispersions were analyzed by a variety of imaging, solid-state, thermal, and solution-state techniques. Dispersions were prepared by both HME and KSD using polyvinylpyrrolidone (PVP) K17 or hydroxypropyl methylcellulose (HPMC) E5. Dispersions were only prepared by KSD using higher molecular weight grades of HPMC and PVP, as these could not be extruded under the conditions selected. Powder X-ray diffraction (PXRD) analysis showed that dispersions prepared by HME were amorphous at 10% and 20% drug load; however, it showed significant crystallinity at 40% drug load. PXRD analysis of KSD samples showed all formulations and drug loads to be amorphous with the exception of trace crystallinity seen in PVP K17 and PVP K30 samples at 40% drug load. These results were further supported by other analytical techniques. KSD produced amorphous dispersions at higher drug loads than could be prepared by HME, as well as with higher molecular weight polymers that were not processable by HME, due to its higher rate of shear and torque output.     

Sugar End-Capped Poly-d,l-lactides as Excipients in Oral Sustained Release Tablets

Sugar end-capped poly-d,l-lactide (SPDLA) polymers were investigated as a potential release controlling excipient in oral sustained release matrix tablets. The SPDLA polymers were obtained by a catalytic ring-opening polymerization technique using methyl α-d-gluco-pyranoside as a multifunctional initiator in the polymerization. Polymers of different molecular weights were synthesized by varying molar ratios of monomer/catalyst. The matrix tablets were prepared by direct compression technique from the binary mixtures of SPDLA and microcrystalline cellulose, and theophylline was used as a model drug. The tablet matrices showed in vitro reproducible drug release profiles with a zero-order or diffusion-based kinetic depending on the SPDLA polymer grade used. Further release from the tablet matrices was dependent on the molecular weight of the SPDLA polymer applied. The drug release was the fastest with the lowest molecular weight SPDLA grade, and the drug release followed zero-order rate. With the higher molecular weight SPDLAs, more prolonged dissolution profiles for the matrix tablets (up to 8–10 h) were obtained. Furthermore, the prolonged drug release was independent of the pH of the dissolution media. In conclusion, SPDLAs are a novel type of drug carrier polymers applicable in oral controlled drug delivery systems.     

Dissolution improvement of high drug-loaded solid dispersion

This study focused on an investigation of a high drug-loaded solid dispersion system consisting of drug, carrier, and surfactant. Solid dispersions of a water-insoluble ofloxacin (OFX) with polyethylene glycol (PEG) of different molecular weights, namely binary solid dispersion systems, were prepared at drug to carrier not less than 5∶5. Polysorbate 80, a nonionic surfactant, was incorporated into the binary solid dispersion systems as the third component to obtain the ternary solid dispersion systems. The powder x-ray diffraction and differential scanning calorimetric studies indicated that crystalline OFX existed in the solid dispersions with high drug loading. However, a decreased crystallinity of the solid dispersions obtained revealed that a portion of OFX was in an amorphous state. The results indicated a remarkably improved dissolution of drug from the ternary solid dispersion systems when compared with the binary solid dispersion systems. This was because of polysorbate 80, which improved wettability and solubilized the non-molecularly dispersed or crystalline fraction of OFX.     

Intermolecular interaction and morphology investigation of drug loaded ABA-triblock copolymers with different hydrophilic/lipophilic ratios

Copolymers with different hydrophilic/lipophilic ratios (HLR) were used to optimize the compatibility between polymer as drug carrier and quercetin as lipophilic drug. Synthesis of amphiphilic triblock copolymers (TC) of poly(butylene adipate)–poly(ethylene glycol)–poly(butylene adipate) (PBA–PEG–PBA) with different PBA molecular weights is the first approach for this purpose. Polymerization and structural features of the polymers were analyzed by different characterization techniques (GPC, ¹H NMR and FT-IR). Formation of hydrophobic and hydrophilic domains with different ratios in the ABA-triblock copolymers was studied by ¹H NMR. The sunflower-like nanoparticles were prepared by self-assembling of the amphiphilic copolymers in the aqueous solution. The hydrophobic PBA segments formed the central solid-like core which stabilized by the hydrophilic PEG rings. The optimum HLR for these copolymers was determined on the basis of drug release time and profile, obtained from freeze-dried nanoparticle powders. The results indicated that optimum HLR for the sustained quercetin release obtained at higher molecular weight of polyesteric domains. Zeta potential measurements showed that the nanoparticle size was close related to the initial concentrations of the nanoparticle dispersions and the compositions of the triblock copolymers. Moreover, TEM pictures showed that the nanocarriers morphologies were changed by changing HLR of triblock copolymers. The PBA–PEG–PBA nanoparticles also showed good drug loading properties, suggesting that they were very suitable as delivery devices for hydrophobic drugs.     

A Menthol-Based Solid Dispersion Technique for Enhanced Solubility and Dissolution of Sulfamethoxazole from an Oral Tablet Matrix

A menthol-based solid dispersion was designed to improve the intrinsic solubility of the poorly soluble sulfamethoxazole- a class II drug molecule of Biopharmaceutics Classification System (BCS) displaying widespread antibacterial activity. Solid dispersions of menthol and sulfamethoxazole were compressed with hydroxypropyl methylcellulose (HPMC) into suitable sulfamethoxazole-loaded matrix tablets for oral drug delivery. The sulfamethoxazole-loaded solid dispersions and compressed tablets were characterized for their physicochemical and physicomechanical properties such as changes in crystallinity, melting point, molecular transitions, and textural analysis for critical analysis of their effects on the solubility and dissolution of sulfamethoxazole. The formulations were further evaluated for swelling, degradation, solubility, and in vitro drug release behavior. In vitro drug release from the sulfamethoxazole-loaded matrix tablets displayed a minimum and maximum fractional release of 0.714 and 0.970, respectively. The tablets further displayed different release rate profiles over the study periods of 12, 16, 48, and 56 h which were attributed to the varying concentrations of menthol within each formulation. Menthol was determined as a suitable hydrophilic carrier for sulfamethoxazole since it functioned as a solubilizing and release-retarding agent for improving the solubility and dissolution of sulfamethoxazole as well as controlling the rate at which it was released.KEY WORDS: crystallinity, menthol, oral solubility and dissolution, solid dispersion, sulfamethoxazole     

Diazepam-Loaded Solid Lipid Nanoparticles: Design and Characterization

The aim of the present study was to investigate the feasibility of the inclusion of a water-insoluble drug (diazepam, DZ) into solid lipid nanoparticles (SLNs), which offer combined advantages of rapid onset and prolonged release of the drug. This work also describes a new approach to prepare suppositories containing DZ-loaded SLN dispersions, as potential drug carrier for the rectal route. Modified high-shear homogenization and ultrasound techniques were employed to prepare SLNs. The effect of incorporation of different concentrations of Compritol® ATO 888 or Imwitor® 900K and Poloxamer 188 or Tween 80 was investigated. Results showed that varying the type or concentration of lipid matrix or surfactant had a noticeable influence on the entrapment efficiencies, particle size, and release profiles of prepared SLNs. Differential scanning calorimetry and X-ray diffraction measurements showed that the majority of SLNs possessed less ordered arrangements of crystals than the corresponding bulk lipids, which was favorable for increasing the drug loading capacity. Transmission electron microscopy and laser diffractometry studies revealed that the prepared nanoparticles were round and homogeneous and 60% of the formulations were less than 500 nm. Additionally, SLN formulations showed significant (P?in vitro release of DZ from the suppositories prepared using DZ-loaded SLN dispersions (equivalent to 2 mg DZ) was significantly (P?相似文献   

Comparative Studies on Chitosan and Polylactic-co-glycolic Acid Incorporated Nanoparticles of Low Molecular Weight Heparin

This study was performed to test the feasibility of chitosan and polylactic-co-glycolic acid (PLGA) incorporated nanoparticles as sustained-release carriers for the delivery of negatively charged low molecular weight heparin (LMWH). Fourier transform infrared (FTIR) spectrometry was used to evaluate the interactions between chitosan and LMWH. The shifts, intensity, and broadening of the characteristic peaks for the functional groups in the FTIR spectra indicated that strong interactions occur between the positively charged chitosans and the negatively charged LMWHs. Three types of LMWH nanoparticles (NP-1, NP-2, and NP-3) were prepared using chitosan with or without PLGA: NP-1 nanoparticles were formed by polyelectrolyte complexation after single mixing, NP-2 nanoparticles were prepared by polyelectrolyte complexation after single emulsion–diffusion–evaporation, and NP-3 nanoparticles were optimized by double emulsion–diffusion–evaporation. NP-3 nanoparticles of LMWH prepared by the emulsion–diffusion–evaporation method showed significant differences in particle morphology, size, zeta potential, and drug release profile compared to NP-1 nanoparticles formed by polyelectrolyte complexation. Another ionic complex of LMWH with chitosan-incorporated PLGA nanoparticles (NP-2) showed lower drug entrapment efficiency than that of NP-1 and NP-3. The drug release rate of NP-3 was slower than the release rates of NP-1 and NP-2, although particle morphology of NP-3 was similar to that of NP-2. Cell viability was not adversely affected when cells were treated with all three types of nanoparticles. The data presented in this study demonstrate that nanoparticles formulated with chitosan–PLGA could be a safe sustained-release carrier for the delivery of LMWH.Key words: chitosan, low molecular weight heparin, nanoparticles, PLGA     

Use of Polyvinyl Alcohol as a Solubility Enhancing Polymer for Poorly Water-Soluble Drug Delivery (Part 2)

The KinetiSol® Dispersing (KSD) technology has enabled the investigation into the use of polyvinyl alcohol (PVAL) as a concentration enhancing polymer for amorphous solid dispersions. Our previous study revealed that the 88% hydrolyzed grade of PVAL was optimal for itraconazole (ITZ) amorphous compositions with regard to solid-state properties, non-sink dissolution performance, and bioavailability enhancement. The current study investigates the influence of molecular weight for the 88% hydrolyzed grades of PVAL on the properties of KSD processed ITZ:PVAL amorphous dispersions. Specifically, molecular weights in the processable range of 4 to 18 mPa · s were evaluated and the 4-88 grade provided the highest AUC dissolution profile. Amorphous dispersions at 10, 20, 30, 40, and 50% ITZ drug loads in PVAL 4-88 were also compared by dissolution performance. Analytical tools of diffusion-ordered spectroscopy and Fourier transform infrared spectroscopy were employed to understand the interaction between drug and polymer. Finally, results from a 30-month stability test of a 30% drug loaded ITZ:PVAL 4-88 composition shows that stable amorphous dispersions can be achieved. Thus, this newly enabled polymer carrier can be considered a viable option for pharmaceutical formulation development for solubility enhancement.KEY WORDS: amorphous solid dispersion, itraconazole, polyvinyl alcohol, PVAL, solubility enhancement     

Rehydrated Lyophilized Rifampicin-Loaded mPEG–DSPE Formulations for Nebulization

Rifampicin-loaded nanoparticles were prepared using two different molecular weights of poly-(ethylene oxide)-block-distearoyl phosphatidyl-ethanolamine (mPEG2000–DSPE and mPEG5000–DSPE) polymers. Particle sizes of all formulations studied were in the range of 162–395 nm. The entrapment efficiency (EE) was not affected by the copolymer’s molecular weight, and the highest EE (100%) was obtained with drug to copolymer ratio of 1:5. The differential scanning calorimetry (DSC) thermograms showed Tg of rifampicin-loaded PEG–DSPE nanoparticles that shifted to a lower value, indicating entrapment of rifampicin in polymer matrix. The Fourier transformed infrared spectra revealed no chemical interactions between the drug and both copolymers. The in vitro drug release from the formulations occurred over 3 days and followed first-order release kinetic and Higuchi diffusion model. The nebulization of rehydrated lyophilized rifampicin mPEG–DSPE formulations had mass median aerodynamic diameter of 2.6 μm and fine particle fraction of 42%. The aerodynamic characteristic of the preparations was not influenced by the molecular weight of the copolymers. Therefore, it is suggested that both mPEG–DSPE are promising candidates as rifampicin carrier for pulmonary delivery.     

Klucel? EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology

The objective of this research work was to evaluate Klucel™ hydroxypropylcellulose (HPC) EF and ELF polymers, for solubility enhancement as well as to address some of the disadvantages associated with solid dispersions. Ketoprofen (KPR), a Biopharmaceutics Classification System class II drug with poor solubility, was utilized as a model compound. Preliminary thermal studies were performed to confirm formation of a solid solution/dispersion of KPR in HPC matrix and also to establish processing conditions for hot-melt extrusion. Extrudates pelletized and filled into capsules exhibited a carrier-dependent release with ELF polymer exhibiting a faster release. Tablets compressed from milled extrudates exhibited rapid release owing to the increased surface area of the milled extrudate. Addition of mannitol (MNT) further enhanced the release by forming micro-pores and increasing the porosity of the extrudates. An optimized tablet formulation constituting KPR, MNT, and ELF in a 1:1:1 ratio exhibited 90% release in 15 min similar to a commercial capsule formulation. HPC polymers are non-ionic hydrophilic polymers that undergo polymer-chain-length-dependent solubilization and can be used to enhance solubility or dissolution rate of poorly soluble drugs. Dissolution/release rate could be tailored for rapid-release applications by selecting a suitable HPC polymer and altering the final dosage form. The release obtained from pellets was carrier-dependent and not drug-dependent, and hence, such a system can be effectively utilized to address solubility or precipitation issues with poorly soluble drugs in the gastrointestinal environment.Key words: hot-melt extrusion, Klucel™ EF/ELF, solid solutions/dispersions, solubility enhancement, thermal miscibility evaluation     

Development of Itraconazole Tablets Containing Viscous KinetiSol Solid Dispersions: <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Analysis in Dogs

The formulation factors relevant to developing immediate and controlled release dosage forms containing poorly soluble drugs dispersed in amorphous systems are poorly understood. While the utility of amorphous solid dispersions is becoming apparent in the pharmaceutical marketplace, literature reports tend to concentrate on the development of solid dispersion particulates, which then must be formulated into a tablet. Amorphous solid dispersions of itraconazole in high molecular weight hydroxypropyl methylcellulose were prepared by KinetiSol® Dispersing and tablets were formulated to immediately disintegrate or control the release of itraconazole. Formulated tablets were evaluated by two non-sink dissolution methodologies and the dosage form properties that controlled the gelling tendency of the dispersion carrier, hydroxypropyl methylcellulose, were investigated. Selected formulations were evaluated in an exploratory beagle dog pharmacokinetic study; the results of which indicate potential for a prolonged absorption phase relative to the commercially extruded control.     

Dissolution Properties and Physical Characterization of Telmisartan–Chitosan Solid Dispersions Prepared by Mechanochemical Activation

Solid dispersion systems of telmisartan (a poorly water-soluble antihypertension drug) with biopolymer carrier chitosan have been investigated in this study. The mechanism of solubilization of chitosan for drug has been studied. In addition, the influence of several factors was carefully examined, including the preparation methods, the drug/carrier weight ratios, and the milling time. Drug dissolution and physical characterization of different binary systems were studied by in vitro dissolution test, particle size distribution, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, and scanning electron microscopy. The results presented that the weak basic property of chitosan appeared as the main driving force for the drug dissolution enhancement. Other effects such as decreased drug crystallinity and size played a positive contributory role. Among the preparation methods, cogrinding was the best method showing strong drug amorphization, reduced particle size, and enhanced dissolution. The drug dissolution markedly improved with increasing the amount of chitosan in solid mixtures. As a result, a significant effect of chitosan increasing telmisartan dissolution has been demonstrated, and cogrinding in a roll ball mill was the best way to prepare solid dispersions, which had high degree of uniformity in drug content and had a practical application in manufacturing.     

Preparation of solid dispersions of nonsteroidal anti-inflammatory drugs with acrylic polymers and studies on mechanisms of drug-polymer interactions

This work studied the mechanisms of interaction between Eudragit RS100 (RS) and RL100 (RL) polymers with 3 nonsteroidal anti-inflammatory drugs: diflunisal (DIF), flurbiprofen (FLU), and piroxicam (PIR). Solid dispersions of polymers and drugs at different weight ratios were prepared by coevaporation of their ethanol solutions. The resulting coevaporates were characterized in the solid state (Fourier-transformed infrared spectroscopy (FT-IR) IR, differential scanning calorimetry, powder-x-ray diffractometry) as well as by studying the in vitro drug release in a gastroenteric environment. Absorption tests from drug solutions to the solid polymers were also performed to better explain the mechanism of interactions between them. The preparative conditions did not induce changes in the crystalline state of the drugs (amorphization or polymorphic change). Drugs strongly interacted with the ammonium groups present in polymers, giving an electrostatic interaction that reinforced the mere physical dispersion of drug molecules within polymer networks. Such interactions are related to the chemical structure of the drugs and to their dissociated or undissociated state. The dispersion of drugs in the polymer matrices strongly influenced their dissolution rate, which appeared slower and more gradual than those of the pure drugs, when polymer ratios were increased. RL coevaporates usually displayed higher dissolution rates. The kinetic evaluation of the dissolution profile, however, suggested that both the drug solubility in the external medium and its diffusion capacity within the polymer network are involved. In the sorption experiments, RL showed a greater adsorptive capacity than RS, in relation to the greater number of quaternary ammonium functions, which behave as activity sites for the electrostatic interactions. In the presence of Tris-HCl buffer (pH 7.4), drug adsorption was reduced, as a consequence of the competition of the chloride ions with drug anions for the polymer binding sites. In general, DIF and FLU displayed a similar interaction with RS and RL active sites; PIR's was different. The different molecular structures of these agents can justify such findings. The presence of a carboxyl group (instead of another dissociable acidic moiety, like the hydroxy-enolic one in the PIR molecule) could help explain the strong interaction with RS and RL polymers' quaternary ammonium centers. Preliminary studies like ours are important in helping develop better forecasting and increasing the understanding of the incorporation/release behavior of drugs from particulate delivery systems that can be made from these polymers.     

Examination of aqueous oxidized cellulose dispersions as a potential drug carrier: II. In vitro and in vivo evaluation of phenylpropanolamine release from microparticles and pellets

The purpose of this research is to investigate the release of phenylpropanolamine from oxidized cellulose-phenylpropanolamine (OC-PPA) complexes prepared using aqueous OC dispersions (degree of neutralization, DN, 0–0.44) and phenylpropanolamine-hydrochloride (PPA.HC1) (concentration, 0.5 M or 1.4 M) in vitro and in vivo. The results showed a faster drug release from the OC-PPA complex made using the OC dispersion with a DN value of 0.22 than from those prepared using dispersions with DN values of 0.29 to 0.44. No significant difference existed between the release profiles of OC-PPA microparticles made using OC dispersions with DN values of 0.29 to 0.44 OC-PPA complexes that contained smaller size particles or higher drug levels, or that were processed by freeze drying released PPA faster. Compared with microparticles, the pellets of OC-PPA complexes released PPA more slowly initially. An increase in pH or ionic strength of the dissolution medium increased the release of PPA, which is attributable to increased polymer hydration and solubilization at higher pH and ionic strength conditions. The OC-PPA pellets implanted subcutaneously in rats released 100% of their PPA in 9 to 12 hours. Agood correlation was found between the in vivo and in vitro release data. Tissue pathology results showed no significant inflammatory tissue reactions. In conclusion, the partially ionized aqueous OC dispersions have the potential to be used as an implantable biodegradable carrier for amine drugs.     

Dissolution and Solid-State Characterization of Poorly Water-Soluble Drugs in the Presence of a Hydrophilic Carrier

The aim of this study was to investigate the effects of a hydrophilic carrier on the solid-state and dissolution characteristics of poorly water-soluble drugs. Three poorly water-soluble drugs, ibuprofen, carbamazepine, and nifedipine, were studied in combination with hydroxypropyl cellulose (HPC), a low molecular weight hydrophilic polymer, without the use of solvent. A 1:1 drug–polymer ratio was used to evaluate the percent drug release, crystallinity, and wettability. A drug–polymer ratio of 1:4 was also used in co-grinding process to evaluate the effect of polymer levels on drug release. Dissolution studies were carried out in deionized water. Mean dissolution time (MDT) was calculated, and statistical analysis of MDTs was done following a single factor one-way analysis of variance. The dissolution rate of the drugs was enhanced by several folds by the simple process of co-grinding with HPC. X-ray diffraction studies were done to investigate the effects of physical and co-ground mix with HPC on the crystallinity of the drugs, which indicated a partial loss in crystallinity upon grinding. Differential scanning calorimetry studies were performed in order to identify possible solid-state interactions between the respective drugs and HPC. Wettability of the drugs by a 0.5% aqueous HPC solution was compared with that of water and n-hexane using the “Washburn method.” Increased wetting and hydrophilization of the drugs by HPC, enlarged surface area due to particle size reduction, and a decrease in the degree of crystallinity were identified as the likely contributors to dissolution rate enhancement.     

Preparation and characterization of biopolymeric nanoparticles used in drug delivery

Nanotechnology plays an important role in advanced biology and medicine research particularly in the development of potential site-specific delivery systems with lower drug toxicity and greater efficiency. These include microcapsules, liposomes, polymeric microspheres, microemulsions, polymer micelles, hydrogels, solid nanoparticles etc. In the present study, preparation and characterization of biopolymeric gelatin nanoparticles for encapsulating the antimicrobial drug sulfadiazine and its in vivo drug release in phosphate buffer saline (PBS) have been investigated. The nanoparticles prepared by second desolvation process varied in a size range 200 nm and 600 nm with a drug entrapment efficiency of 50% characterized by atomic force microscopy and dynamic light scattering. The drug release from the nanoparticles occurred up to 30% in a controlled manner.     

Solid-state NMR investigation of indomethacin-cyclodextrin complexes in PEG 6000 carrier

Various solid dispersions of alpha-, beta- and gamma-cyclodextrin (CD) in PEG 6000 with and without the addition of 5% w/w indomethacin were prepared by the melting method using the original components. The samples were investigated by solid-state (13)C NMR, and the interactions between the drug and the cyclodextrins were evaluated. The indomethacin-gamma-CD phase with tetragonal symmetry found in a previous X-ray study gave chemical shifts which suggested that this phase is a complex between indomethacin and gamma-CD. Evidence of an indomethacin-beta-CD complex were found. A distribution of the chemical shifts for beta-CD was attributed to the possible formation of different types of complexes between indomethacin and beta-CD. No complex formation was found in the alpha-CD system. The degree of relative crystallinity of the samples in the gamma-CD system was measured by (1)H NMR, X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and modulated-temperature DSC (MTDSC). The results obtained by the NMR, XRD, and DSC techniques showed that the dispersions were less crystalline than the pure polymer carrier, and the dispersion containing the indomethacin-gamma-CD complex had the lowest degree of crystallinity. By the MTDSC method a deviation was found for the PEG 6000/indomethacin dispersion. This emphasizes that the different techniques give specific information on the crystallinity.     

Formation of Inhalable Rifampicin–Poly(l-lactide) Microparticles by Supercritical Anti-solvent Process

Formation of inhalable microparticles containing rifampicin and poly(l-lactide) (L-PLA) by using supercritical anti-solvent process (SAS) was investigated. The solutions of drug and polymer in methylene chloride were sprayed into supercritical carbon dioxide. The effect of polymer content and operating conditions, temperature, pressure, carbon dioxide molar fraction, and concentration of solution, on product characteristics were studied. The prepared microparticles were characterized with respect to their morphology, particle size and size distribution, drug content, drug loading efficiency, and drug release characteristic. Discrete, spherical microparticles were obtained at high polymer:drug ratios of 7:3, 8:2, and 9:1. The shape of L-PLA microparticles became more irregular and agglomerated with decreasing polymer content. Microparticles with polymer content higher than 60% exhibited volumetric mean diameter less than 5 μm, but percent drug loading efficiency was relatively low. Drug-loaded microparticles containing 70% and 80% L-PLA showed a sustainable drug release property without initial burst release. Operating temperature level influenced on mean size and size distribution of microparticles. The operating pressure and carbon dioxide molar fraction in the range investigated were unlikely to have an effect on microparticle formation. An increasing concentration of feed solution provided larger size microparticles. Rifampicin-loaded L-PLA microparticles could be produced by SAS in a size range suitable for dry powder inhaler formulation.