Assessing the Rehabilitation of Achilles Tendon Ruptures using Modified Teuffer and Lindholm Technique.

The aim of this study is to assess the optimum rehabilitation and the functional outcome of open repaired Achilles tendon ruptures. This study was conducted for the 18 consecutive patients of complete ruptures at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from 2012 to 2013. Two groups were considered during 6 to 18 months post-operative observation and each group consist 9 patients. In the Group I, modified Teuffer's and in Group II, Lindholm operative methods were employed for the open repair of Achille tendon. The post operative outcomes were assessed for both of the groups through the modified Thermann's scores. In this study the patients median age was seen 39 years with 72.2% male and 27.8% female. The Thompson test was found positive in pre-operative and negative in post-operative outcome. The results shown that Achilles tendon ruptures occurred in 4 to 6cm rupture site, where the rupture side was 61.1% left and 38.9% right. The subjective overall assessment of total Thermann's scores were found very good (91 to 96) in 4 cases and (90 to 98) in 3 cases for Group I and Group II, respectively. Both of the operative techniques were found accountable results for rehabilitation. Therefore, based on the further statistical evidence of higher correlations and errors it may be concluded that Achilles tendon ruptures can be treated by modified Teuffer's or Lindholm technique.

Surgical Outcome of Intradural Spinal Tumors.

Results of 63 surgically treated intradural spinal tumors between the period of October 2003 and December 2014 at Bangabandhu Sheikh Mujib Medical University (BSMMU) and in our private settings, Dhaka, were analyzed retrospectively. There were 33 males, 30 females with an average age of 52.4 years (13-70 years) and followed up for at least a year. The preoperative symptom with duration, tumors location and intradural space occupancy and the histopathological diagnosis were analyzed. Pain was evaluated by the visual analogue scale (VAS) and the neurologic function was assessed by Nurick's grade. The tumors were located as, thoracic (n=32, 50.79%), lumbar (n=16, 25.39%), cervical (n=05, 07.93%), and junctional (n=10, 15.87%, CervicoThoracic-01, Thoracolumbar-09). The histopathological diagnosis included schwannoma (n=30, 47.7%), meningiomas (n=14, 22.3%), neurofibroma, arachnoid cyst and myxopapillary ependymoma (n=03, 04.76%) each and paraganglioma (n=01, 01.59%). Among the intramedullary tumors, ependymoma (n=03, 04.76%), astrocytoma and epidermoid cyst (n=02, 03.17%), haemangioblastoma, paraganglioma and cavernous haemangioma (n=01, 01.59%) each. The VAS score was reduced in all cases from 8.0±1.2 to 1.2±0.8 (p<0.003) and the Nurick's grade was improved in all cases from 3.0±1.3 to 1.0±0.0 (p<0.005). The preoperative neurological deficit improved within 8 postoperative weeks in most cases and within 1 postoperative year in all cases. Complications included cerebrospinal fluid leakage, parasthesia and further neurological deterioration (Astrocytoma) (n=02, 03.17%) and dependant bedsore and recurrence (Ependymoma) (n=01, 01.59%). Aggressive surgical excision potentially minimizes neurologic morbidity and improved outcome except intramedullary tumors where initial treatment consists of maximum safe surgical resection or biopsy.

Influence of the co-encapsulation of different excipients on the properties of polyester microparticle-based vaccine against brucellosis.

This work evaluates the influence of different pharmaceutical auxiliaries (Pluronic F68, polyvinylpyrrolidone [PVP] or Tween 20), when mixed with an antigenic extract from Brucella ovis (hot saline; HS), on the characteristics of the resulting poly(epsilon-caprolactone) (PEC) and poly(lactide-co-glycolide) (PLGA) microparticles. In all cases, PEC microparticles were smaller than PLGA ones. Concerning the HS loading, PLGA microparticles were highly dependent on the type of the excipient used, whereas all the PEC formulations displayed similar encapsulation efficiencies. For both types of microparticles, the presence of PVP induced a burst release effect. On the contrary, the use of Tween 20 or Pluronic F68 dramatically modified this profile. For PLGA-Tween 20 and PEC-Pluronic F68 microparticles, the HS was released in a pulsatil way during the first 7 days followed by a continuous release for at least 3 weeks. The antigenicity of the HS components was kept in all cases. Phagocytosis by murine monocytes showed a clear difference based just on the hydrophobicity of the polymer, being PEC microparticles better engulfed. Cell activation quantified by the release of H2O2 did not showed major differences between batches, however, microparticles of PEC and Pluronic F68 induced the highest nitric oxide production. Together, these results confirm the advantageous qualities of the "HS-PEC-Pluronic F68 microparticles" as favorable candidate for vaccine purposes against brucellosis.

Modulation of the cellular immune response after oral or subcutaneous immunization with microparticles containing Brucella ovis antigens.

An antigenic extract (HS) from Brucella ovis was encapsulated in either poly-epsilon-caprolactone (PEC) or poly-lactic-co-glycolic acid 75:25 (PLGA) microparticles containing beta-cyclodextrin and Pluronic F-68 as stabilising agents. The resulting microparticles displayed sub-5 microm sizes. Antigen loading was 5.2 and 3.8 microg/mg for HS-PEC and HS-PLGA microparticles, respectively. Specific HS cytokine profiles were determined after subcutaneous and oral immunisation of BALB/c mice. Gut distribution studies of the formulations after oral administration showed that HS-PEC microparticles interacted more strongly with mucosa and Peyer's patches than HS-PLGA. Accordingly, oral immunisation with HS-PLGA induced a negligible immune response, whereas HS-PEC elicited a Th1 response although of low intensity. Subcutaneous immunisation with HS-PEC induced high IFN-gamma and IL-2 release; in contrast, HS-PLGA particles induced a Th2 profile characterized by significant levels of IL-4. Splenic cells from free-HS immunised mice released IFN-gamma and IL-2 but not IL-4. A less intense Th1 pattern was also found from HS stimulated nai;ve splenic cells. These results suggest that the HS itself possesses Th1 immunopotentiating properties, required to control brucellosis, that can be specifically increased by encapsulation in PEC microparticles. In contrast, PLGA microparticles modulate the response toward a Th2 pathway.

Solid dispersions of diflunisal-PVP: polymorphic and amorphous states of the drug.

Coprecipitates of diflunisal and polyvinylpyrrolidone (PVP K15, K30, and K90) and physical mixtures were studied using x-ray diffraction analysis, infrared (IR) spectroscopy, differential scanning calorimetry (DSC), and hot-stage microscopy. X-ray diffraction results revealed an almost amorphous state, even in coprecipitates with a high content of drug, next to 70%, which was independent of the polymer molecular weight. The IR spectra of 70:30 drug-PVP solid dispersions suggest the formation of diflunisal-PVP hydrogen bonds. For 70:30 drug-polymer ratio, the physical mixture showed linear dissolution kinetics of free crystals, but the corresponding coprecipitates exhibit two different dissolution processes. When the 25:75 drug-polymer dispersion is analyzed by hot-stage microscopy, only solid plates of PVP are observed; the absence of drug particles may be due to a molecular dispersion of the drug into the polymer. Moreover, polymorphic changes of diflunisal were detected in the solid dispersions in comparison with the corresponding physical mixtures, which are always formed by polymorph II. At high concentrations of drug (75:25 and 80:20), x-ray diffraction patterns of solid dispersions showed the partial recrystallization of the drug, displaying the main diffraction peaks of polymorph I when ethanol was used as coprecipitation solvent, whereas diflunisal form IV was obtained in chloroform.

Development of microparticles prepared by spray-drying as a vaccine delivery system against brucellosis.

The antigenic extract Hot Saline from Brucella ovis was microencapsulated by the spray-drying technique with different polyesters (poly-lactide-co-glycolide RG502H [PLGA], and blends with poly- epsilon -caprolactone [PEC]) in order to obtain microparticles smaller than 5 microm. Microparticles were tested for encapsulation efficiency, release studies, acidification of the in vitro release medium, and in vitro J744-macrophage experiments (phagocytosis and toxicity of the preparations) to determine the optimal formulation for vaccination purposes. Formulation containing no PCL showed the highest encapsulation efficiency, although the differences were not significant. The in vitro release kinetics were characterized by a high burst effect after 1 h of incubation, followed by a slow and continuous release. For the formulation based on PLGA, the pH of the medium during release dropped from 7.4 to 3.5 while the presence of PEC attenuated the pH drop. All formulations showed light toxicity by the MTT assay, but differences were observed in terms of phagocytosis, as particles prepared with PEC showed the higher uptake by J744-macrophages and cell respiratory burst, determined by oxygen peroxide release. All these characteristics suggest that the microparticulated antigenic formulation containing the higher ratio of PEC is susceptible to be used in animal vaccination studies.

Polyester microparticles as a vaccine delivery system for brucellosis: influence of the polymer on release, phagocytosis and toxicity.

Microparticles, containing an antigenic complex from Brucella ovis (HS), were evaluated for vaccine purposes against brucellosis. They were prepared by the double emulsion solvent evaporation method using two different polyesters, poly-lactide-co-glycolide acid (75:25; RG 756) and poly-epsilon-caprolactone. The encapsulation efficiency and release of HS from the microparticles, their capacity to be phagocytosed and also their toxicity on murine monocytes J774.2 were investigated. Both polymers lead to smooth and spherical sub-5 microm particles, with approximately 30% of the antigen initial dose encapsulated. SDS-PAGE and immunoblot of extracted antigens confirmed that the apparent molecular weight and antigenicity remained unaltered after the encapsulation procedure. However, the in vitro release of the antigens differed among them. The release profile for PLGA microparticles was continuous, whereas PEC ones released the antigens in a triphasic release pattern. Phagocytosis was clearly influenced by the hydrophobicity of the polymer, increasing in the case of PEC microparticles. Toxicity assay showed that both types of microparticles induced similar levels of mitochondrial damage. In conclusion, HS-PEC microparticles could be used as an effective vaccine against brucellosis, as the antigen is released in boosters and they are greatly phagocytosed by macrophages.

A Brucella ovis antigenic complex bearing poly-epsilon-caprolactone microparticles confer protection against experimental brucellosis in mice.

A hot saline antigenic extract (HS) from Brucella ovis was encapsulated in poly-epsilon-caprolactone microparticles (PEC), and tested as a vaccine against B. ovis and B. abortus infections in mice. Subcutaneous but not oral administration in BALB/c mice of the HS-PEC induced high amounts of IFN-gamma and IL-2 but low quantities of IL-4 suggesting a combined Th1/Th2 cellular immune response. The vaccine administered either subcutaneously or orally protected mice against B. ovis infection. Such protection was similar to that provided by the reference living attenuated B. melitensis Rev. 1 vaccine. By contrast, only the subcutaneous vaccination with HS-PEC was as effective as Rev. 1 in conferring protection against B. abortus infection. The use of free HS or empty PEC microparticles did not produce any protective effect.

[Controlled liberation of active principles by means of new galenic formulations]. / Liberación controlada de principios activos mediante el empleo de formulaciones galénicas.

Drugs inside a conventional galenic form are distributed between specific biological targets and other anatomical tissues. With the aim to obtain a more rational and a better therapeutic, one of the most promising possibilities by using the concept of vectorization: association of an active principle to an appropriate vector with the object to increase its action efficiency and efficacy. By this means, they do not just increase the affinity of the drug to the target but also active principle gets protected from a potentially hostile environment (hydrolytic enzymes, acid pH, etc.). The success in the extension of the applications of the vectorización depends more and more of an appropriate design, for what the fundamental objective of this revision will be the one of presenting the general characteristics and some of the current applications in these new galenic forms.

Evidence for polymorphism in glisentide.

The polymorphism of glisentide has been investigated. Three polymorphs (I, II, III) have been prepared by recrystallization from different solvents and other polymorphic form (IV) was obtained by heating polymorph III at 100 degrees C. In addition, two 1:1 stoichiometric solvates containing carbon tetrachloride and dioxane have been crystallized and finally, an amorphous solid has been obtained. It has been observed that the polarity of the recrystallisation solvent and its ability to form hydrogen bonds have a great influence on the polymorphism of glisentide. The different solid forms of glisentide have been characterized using X-ray diffraction analysis, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), IR spectroscopy and optical microscopy. The recrystallization of polymorph I in melted form II and also the transition of form III-IV have been detected by DSC and X-ray diffraction analysis.

Influence of polyethylene glycol 4000 on the polymorphic forms of diflunisal.

The present study was carried out to investigate the physico-chemical characteristics of diflunisal-PEG 4000 solid dispersions prepared by melting, solvent and melting-solvent methods. The solvents chosen were chloroform, methanol and ethanol-water due to the fact that the drug presents different polymorphic forms in these solvents. The characterization of solid dispersions was performed by X-ray powder diffraction because this technique has the advantage over other identification methods that it can detect both drug and ligand simultaneously. The X-ray diffraction patterns of the diflunisal-PEG systems suggested that the drug/polymer ratio and the solvent nature play an important role in the crystallization of the drug. In this regard, diflunisal crystallizes in form I at high concentrations of the drug (drug/polymer 2:1) in the solidified melt dispersions, however, polymorph III is mainly obtained as the polymer content increases (1:1 and 2:3). Likewise, in solid systems obtained by the solvent and melting solvent methods the drug solidifies in form III in ethanol/water and methanol while polymorph IV crystallizes in chloroform. Finally, DSC thermograms and hot-stage microscopy data of solid dispersions prepared by the melting method have allowed to draw the diflunisal-PEG 4000 solid-liquid phase diagram.

Dissolution kinetics for coprecipitates of diflunisal with PVP K30.

Diflunisal is a nonsteroidal anti-inflammatory drug that is poorly soluble in water. The present study describes the formulation of solid dispersions of the drug designed to increase its solubility. X-ray diffraction and DSC were used to examine the physico-chemical characteristics of solid dispersions of diflunisal and polyvinylpyrrolidone (PVP) prepared by the solvent method, using percentage proportional compositions ranging from 20:80 to 50:50. X-ray diffraction analysis detected that diflunisal is present in solid dispersions in crystalline or amorphous state depending on the PVP content. The thermal behavior of diflunisal observed in the DSC curves of solid dispersion systems, was attributed to a solid-state interaction. The increased release of the PVP-drug dispersion as compared to the PVP-drug physical mixture was attributed to the formation of a complex resulting from the interaction of the drug and the polymer.

Preparation and dissolution rate of gliquidone-PVP K30 solid dispersions.

Solid dispersions of gliquidone in PVP K30 were prepared by the solvent method. These dispersions were characterized using X-ray diffraction. In comparison with the drug alone, the physical mixtures and even more the solid dispersions showed an increase in the dissolution rate. Moreover these solid dispersions were stable during storage.

Solubilization and interaction of sulindac with polyvinylpyrrolidone K30 in the solid state and in aqueous solution.

In this report the interactions of sulindac with polyvinylpyrrolidone K30 (PVP K30), both in the solid state and in aqueous solution, have been investigated. Solid dispersions of sulindac with PVP K30 were prepared by the solvent method in ethanol from various drug-to-polymer weight ratios. X-ray powder diffraction and differential scanning calorimetry have shown that PVP inhibits the crystallization of sulindac. The stabilization of the noncrystalline state of sulindac was shown by x-ray diffractometry after a 1-year storage. There was a considerable increase in the release rate of the drug when the polymer content was increased and the intrinsic dissolution rate values of these systems were calculated. From the UV spectra a bathochromic shift and a well-defined isosbestic point were observed at pH 2 and 6, which confirmed an interaction between the drug and the polymer in solution. Moreover, the apparent solubility of sulindac has been modified as a function of the polymer concentrations. The binding process between the drug and PVP was exothermic from the stability constant values at 25, 30, and 37 degrees C at pH 2.

Solubilization and interaction of sulindac with beta-cyclodextrin in the solid state and in aqueous solution.

A sulindac-beta-cyclodextrin complex was obtained by the coprecipitation method. Kneaded solids and physical mixtures were also prepared. The complex was shown by x-ray powder diffraction to be noncrystalline whereas pure drug and any of the other sulindac-beta-CD system were crystalline. the endothermic peak of sulindac due to the fusion of drug disappeared in DSC thermograms for the coprecipitate product, which confirmed the interaction between sulindac and beta-CD in the solid state. After a 1-year storage drug crystals could not be observed by x-ray diffractometry, which indicated that the complex formed was stable. The complex showed the fastest dissolution rate which might be attributed to the high-energy noncrystalline state and the inclusion complex formation in solution. UV spectra were modified and the apparent solubility of the drug increased with the addition of beta-CD, which confirmed the interaction between sulindac and the ligand in solution. The apparent stability constant, K1:1, for the complex at pH 2 and 25, 30, and 37 degrees C was 340, 220, and 160 M-1, respectively, which confirmed the influence of temperature on the complex stability. The value of K1:1 at pH 6 and 25 degrees C was 139 M-1, which indicated that the complex is formed easier with the non-ionized sulindac. The enthalpy change, delta H degree, showed that the binding process is exothermic.

Polymorphism of sulindac: isolation and characterization of a new polymorph and three new solvates.

The polymorphism of sulindac was investigated. Two polymorphs (I and II) and a new crystalline form (form III) of sulindac were prepared by recrystallization in different solvents. In addition, three new pseudopolymorphs (solvates) from acetone, chloroform, and benzene were obtained, with each containing 1 mol of solvent to 2 mol of sulindac. Different sulindac polymorphs and pseudopolymorphs were characterized by X-ray diffractometry, infrared spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and hot-stage microscopy. The transition behavior of the crystalline forms of sulindac, their melting points, and their enthalpies were investigated by DSC. The melting of form II was observed at 184 degrees C, and form I subsequently recrystallized from this melt. Similarly, form III melts at 145 degrees C and then recrystallizes to form I. We also investigated the influence of the crystallization solvent on sulindac crystal shape.

Polymorphism of diflunisal: isolation and solid-state characteristics of a new crystal form.

Three polymorphs (I, II, and III forms) and a new crystal form (form IV) of diflunisal were prepared and characterized by powder X-ray diffractometry, differential scanning calorimetry (DSC), hot-stage microscopy, IR spectroscopy, and dissolution studies. According to the different X-ray diffraction profiles, an identification system for the polymorphs can be developed based on the different peak positions of the diffraction patterns. The mutual transition behavior of the polymorphs was investigated and the melting points and melting enthalpies were determined from DSC and thermomicroscopy data. All forms first recrystallize to the more stable form (form I) and then melt at 210 degrees C; only one weak transition peak was detected corresponding to transformation of form III to form I. Differences observed in IR spectra indicate that intramolecular hydrogen bonding occurs between hydroxyl and carbonyl groups and/or between fluorine atoms. The intrinsic dissolution rates were determined from compressed disks in an aqueous medium. Unexpectedly the dissolution rate of form IV was lower than that of the most stable modification form I.