A self-microemulsifying drug delivery system (SMEDDS) was developed to increase the dissolution rate, solubility, and ultimately bioavailability of a poorly water soluble drug, lovastatin. SMEDDS was thε mixtures of oils, surfactants, and cosurfactants, which emulsify under conditions of gentle agitation, similar to those which would be encountered in the gastro-intestinal (GI) tract. Various types of self-emulsifying formulations were prepared using four types of oil (Capryol 90, Lauroglycol 90, Labrafil M 1944 CS and Labrafil M 2125), two surfactants (Cremophor EL and Tween 80), and three cosurfactants (Carbitol, PEG 400 and propylene glycol). Thε efficiency of emulsification was studied using a laser diffraction size analyzer to determine particle size distributions of the resultant emulsions. Optimized formulations selected for bioavailability assessment were Carpryol 90 (40%), Cremophor EL (30%) and Carbitol (30%). SMEDDS containing lovastatin (20 mg and 5 mg) were compared to a conventional lovastatin tablet $(Mevacor^{\circledR},\;20\;mg/tab)$ by the oral administration as prefilled hard gelatin capsules to fasted beagle dogs for in vivo study. The arεa under the serum concentration-time curve from time zero to the last measured time in serum, $AUC_{0{\rightarrow}24h}$, was significantly greater in SMEDDS, suggesting that bioavailability increase 130% and 192% by the SMEDDS, respectively. The self-emulsifying formulations of lovastatin afforded the improvement in absolute oral bioavailability relative to previous data of lovastatin tablet formulation. These data indicate the utility of dispersed self-emulsifying formulations for the oral delivery of lovastatin and potentially other poorly absorbed drugs.
An, Jung-Mo;Oh, Se-Jong;Cha, Yong-Doo;Kwon, Soon-Yong;Park, Young-Ju;Park, Jun-Woo;Rhee, Gun-Joo
Journal of the Korean Association of Oral and Maxillofacial Surgeons
/
v.26
no.6
/
pp.591-601
/
2000
The objective of this study was to find out whether the unilateral distraction of mandible has an influence on temporomandibular joint and if it does, how significant the influence is. Four beagle dogs were used in this study. Each dog had two implants placed into the left mandible. The mandible was distracted for 14days with an distraction device as an amount of 0.75mm, twice per day after osteotomy between two implants. Each animals were sacrificed at the second, fourth, sixth and eighth week after the total distraction amount of 10.5mm were gotten. Upon embedding and staining, the specimens were evaluated with a light microscope. The results were as follows. 1. For the second week group, the articular cartilage and osteoid seam of temporal bone and condyle were relatively well maintained. There were not any significant differences between distraction side and non distraction side. 2. For the fourth week group, the periosteal reaction was activated and the articular cartilage and osteoid seam of temporal bone and condyle were severely thickened - especially at posterior portion of distraction side. This findings revealed that the unilateral distraction forces has more influence on distraction side than on non distraction side, and on posterior portion than on anterior portion. 3. For the sixth and eighth week group, the thickness of meniscus in distraction side gradually recovered to the initial level. The thickened articular cartilage and osteoid seam of temporal bone and condyle were decreased in distraction side and showed relatively stable in non distraction side. From this results, we suggest that several considerations are required such as using an occlusal splint, maintaining the stability of bone distraction device and evaluating bone distraction rate to minimize the damages of temporomandibular joint tissues in early stage of distraction side.
Several effective treatment methods and materials have been developed for the treatment of furcation involvement. Currently, the combination of guided tissue regeneration (GTR) and bone grafts is the most commonly prescribed method of treating furcation involved defects. But because these cases often present with poor accessibility, placement of the membrane may be difficult and consequently, clinically impractical. In this study, the alveolar bone healing patterns of adult beagle dogs presenting with alveolar bone destruction treated by one of two methods - treatment using solely bone allografts (BBP(R)), or treatment using bone allografts (BBP(R)) stabilized by a fibrin adhesive - were comp ared. The effects of the fibrin adhesive on the initial stabilization of the newly formed bone, subsequent regeneration of bone, and the feasibility of the clinical application of the fibrin adhesive were analyzed. The results of the study were as follows: 1. Clinical signs of inflammation at the 4-8 week interval were not observed: but signs of mild inflammation were histologically observed at the 4-week interval. 2. Allografts stabilized by fibrin adhesive showed good bone formation, whereas defects treated with only the allograft material showed incomplete alveolar bone regeneration. 3. Allografts stabilized by fibrin adhesive showed a decrease in the amount old bone with a concurrent increase in the formation of new lamellar bone four weeks post-op, whereas defects treated with only the allograft material showed no new lamellar bone formation at the same interval. 4. In detects treated with only the allograft material, the defective area was filled with connective tissue 8-weeks post-op, whereas fibrin adhesive stabilized allografts showed viable connections between the original bone and the newly formed bone, in addition to neovascularization 8-weeks post-op. The results of this study show that concurrent use of fibrin adhesive materials can stabilize the allograft material and aid in new bone formation Although the stability of fibrin adhesives fall short of the results achievable by GTR membranes, in cases presenting with poor accessibility that contraindicate the use of membranes, fibrin adhesive materials provide a viable and effective alternative to graft stabilization and new bone formation.
Purpose: Platelet derived growth factor(PDGF)-BB and bone morphogenetic protein(BMP)-2 are well-known representative growth factors. The purposes of this study were to investigate the effect of rhPDGFBB and rhBMP-2 on osseointegration of titanium implants at periimplant bone defects grafted with hydroxyapatite and to evaluate the feasibility of imaging bone structures around screw-type titanium implant with micro-CT. Materials and Methods: The first molar and all premolars in the mandible region of four beagle dogs were extracted. Following a healing period of 4 months, three $8{\times}8{\times}6mm$-sized bony defects were formed and screw-type titanium implants were placed with hydroxyapatite(HA) block and growth factors; Control group, PDGF group and BMP group. Two months post-implantation, the mandible was harvested. Bone volume(BV), bone-to-implant contact(BIC) and bone mineral density(BMD) were analyzed with micro-CT and histology. Results: According to micro-CT analysis, BV and BMD measures of PDGF and BMP group were significantly higher than control group(BV; PDGF group: $p{\fallingdotseq}0.011$, BMP group: $p{\fallingdotseq}0.006$/BMD; PDGF group: $p{\fallingdotseq}0.020$, BMP group: $p{\fallingdotseq}0.011$) and BIC measures of BMP group were significantly higher than PDGF group($p{\fallingdotseq}0.015$). In histologic evaluation, BIC measures of BMP group was significantly higher than PDGF group($p{\fallingdotseq}0.048$). The values of BV in histologic sections were higher than in micro-CT images and the values of BIC in micro-CT images were higher than in histologic sections. Conclusion: The findings of this experimental study indicates that the use of rhPDGF-BB and rhBMP-2 can increase new bone formation in a large bony defect around titanium implant, and rhBMP-2 is more effective than rhPDGF-BB. Micro-CT can be considered useful for assessment as a rapid and nondestructive method for 3-dimensional measurement of bone healing around implants. Further study is necessary, however, to remove metal artifacts around titanium implant and to standardize the method.
Journal of Dental Rehabilitation and Applied Science
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v.25
no.3
/
pp.279-285
/
2009
The purpose of this study was to evaluate histologic result of bone substituting materials on extraction sockets. We compare the histologic findings of control, $MBCP^{(R)}$, $Polybone^{(R)}$. Mandibular premolar teeth of Beagle dogs were extracted available for bone filling. All alveolar extraction sockets were thoroughly debrided with surgical curet to remove the periodontal ligament. The graft materials were filled into the extraction sockets. The animals were sacrified 90 days after implantation. Both treated and control mandibular sites were histologically evaluated with light microscopy. Histological observation at 90 days revealed that control and experimental sites were healed uneventfully without any adverse tissue reaction. Regenerated new bone formation ratio is 34.5% for control, 28.4% for $MBCP^{(R)}$, 23.8% for $Polybone^{(R)}$. From this results, it was suggested that $MBCP^{(R)}$, $Polybone^{(R)}$ are promising bone substituting materials to promote normal tissue healing and new bone formation.
The purpose of this study was to evaluate a new biodegradable membrane - atelocollagen as a guided tissue regeneration barrier on the dehiscence defects adjacent to the dental implants. 3 beagle dogs were selected for this study and all the mandibular premolars($P_1,P_2,P_3&P_4$) were extracted. Twelve weeks after the extraction, the edentulous ridges were formed to be placed the titanium plasma-sprayed IMZ implants. Four implant osteotomies were performed on each side of the mandible. The osteotomies were placed facially in the edentulous ridges to approximate an actual dehiscence defect as closely as possible, The standardized dehiscence defects were created 3 mm in width and 4 mm in height by osteotomy. A total 24 implants were placed. e-PTFE, ateloco11agen and $Collatape^{(R)}$ were placed to cover the defects and the one defect served as a control, not covered any membrane. By random selection, three dogs were sacrificed at 2 weeks, 4weeks and 8 weeks after fixation with 3% glutaraldehyde. A week before sacrificing, 8-week dog was infused intravenously with oxy-tetracycline 30mg/kg. The left mandibular blocks were used for full decalcified histologic preparation and the right mandibular blocks were selected for undeca1cified preparation, At 2 weeks, the regenerated bone of e-PTFE and atelocollagen groups appeared to be more dense than other groups and the percentage of bone defect fill was highest for e-PTFE and follwed by ateloco1lagen group. However, the $Collatape^{(R)}$ and control groups showed a little new bone formation. $Collatape^{(R)}$ was almost degraded within 2 weeks. At 4 weeks, the regenerated new bone were much greater and denser than at 2 weeks for e-PTFE and ateloco11agen group. Although a part of atelocollagen bagan to be degraded at the margin and surrounded by foreign body giant cells related to foreign body reaction, it was generally intact and the regenerated new bone was shown much more than at 2 weeks. The amount of new bone in $Collatape^{(R)}$ and control groups at 4 weeks were similar to that of 2 weeks group. At 8 weeks, the regenerated bone was matured and observed along the implant fixture. Direct new bone formation and calcium deposits beneath the e-PTFE were observed. No further bone growth was seen in the $Collatape^{(R)}$ and control groups. In reflected fluoromicrcocopic observation, the osteogenic activity was pronounced between e-PTFE membrane and the old bone. High osteogenic activity was also observed in atelocol1agen group. This study suggested that the ateloco11agen as well as e-PTFE could be used for guided tissue regeneration on dehiscence defects adjacent to the dental implants. But the $Collatape^{(R)}$ was completely resorbed within 2 weeks and was not a suitable membrane for guided bone regeneration.
Background: Crestal bone loss known as saucerization is a frequently observed phenomenon. Recent studies have shown that implants with micothreaded crest module reduced the force concentration in the crestal region thus resulting in no or reduced crestal bone loss. This study presents a clinical, histologic, and histometric evaluation of implants with microthreaded crest module and SLA surface. Methods: The implants were placed in the mandible of 5 beagle dogs weighing 10-15kg. Four premolars were bilaterally extracted 8 weeks prior to implant placement. Mucoperiosteal flap was elevated and drilling with increasing diameter was performed under saline irrigation. After countersinking 2 implants were placed in each side resulting in 4 implants per dog. Healing period of 8 weeks was allowed before sacrificing the animals. Histologic preparation was performed for histologic and histometric analysis. Bone to implant contact as well as percentage of bone area inside threads were measured. T-test was used for statistical analysis with pvalue p<0.05. Results: 1. Healing was uneventful without any cover screw exposure. New bone formation around the implants was observed without any inflammatory infiltration. 2. Bone to implant contact in the microthread and thread were 43.90 ${\pm}$ 20.30 %, and 53.19 ${\pm}$ 20.97 % respectively. The overall bone to implant contact was 48.54 ${\pm}$ 20.95 %. 3. Percentage of bone area inside threads were 54.43 ${\pm}$ 10.39 %, and 38.44 ${\pm}$ 16.44 % for the microthread and thread respectively. There was statistically significant difference(p<0.05). The overall percentage of bone area inside threads was 46.67 ${\pm}$ 15.68 %.
The purpose of this study is to evaluate the biocompatibility and the biorsorbability of several types of calcium polyphosphate made through change of manufacturing process for 12 month. To solve limitation of calcium phosphate, we developed a new ceramic, Calcium Polyphosphate(CPP), and report the biologic response to CPP in extraction sites of beagle dog. Porous CPP blocks were prepared by condensation of anhydrous $Ca(H_2PO_4)_2$ to form non-crystalline $Ca(PO_3)_2$ and then milled to produce CPP powder. CPP powder, CPP block, and CPP granules added with $Na_2O$ were implanted in extraction sockets and histologic observation were performed at 12 months later. Like 3 months results, histologic observation at 12 months revealed that CPP matrix were mingled with and directly apposed to new bone without any adverse tissue reaction, CPP powder show direct bony contact, but new bone formation and fibrous tissue encapsulation showed in CPP block. 10% $Na_2O$ CPP granules show more inflammatory cells infiltration around graft materials compared at 3 month, but 15% $Na_2O$ CPP granules show less. This result revealed that regardless of addition of $Na_2O$, CPP had a high affinity for bone and had been resorbed slowly. From this results, it was suggested that CPP is promising ceramic as a bone substitute and addition of $Na_2O$ help biodegradation but optimal concentration of $Na_2O$ and other additive component to increase degradation rate should be determined in further study.
Abnormal gastric emptying time of dog by alien substance, neoplasm, pyloric antrum hyperplasia, stomach surgery, electrolyte imbalance, stomach-dilated torsion is clinically important as a digestive disease. Therefore study aims to provide basic data on the clinical usefulness of gastric emptying time test which uses radiopaque Kolomark developed in Korea rather than using the existing BIPS for the dog. 9 beagles were used for this experiment and their average weight was about 10.3kg with 2.5 year-old average age. For the test, fast for 12 hours was made without chemical sedation, and just before the test, 1 capsule of Kolomark was fed with 25% of daily feed amount, and we took photographs at ventrodorsal and right lateral position after 2, 4, 8 and 12 hours. As for interested reading area, we observed entire stomach from cardia to stomach pyloric part, and as for analysis method, we counted Kolomarks remained in the stomach per time and judged only P value below 0.05 to be meaningful by using Friedman Test. After feeding Kolomark through oral cavity, it took average 7.55 hours for the Kolomark to have escaped from the stomach to small intestine. In this study of gastrointestinal tract passing time after feeding matured dog, we used Kolomark and expect that it could be a basic data for normal gastrokinetic time.
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