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At least 253 records · Page 14Linked to original sources

PubMed1998

Tensile strength of lens capsules in eye-bank eyes.

PURPOSE: To measure the tensile strength of the anterior and posterior lens capsules in eye-bank eyes and study the tensile strength of capsules dehydrated with hypertonic glucose solution. SETTING: Tongren Hospital, Beijing, China. METHODS: The in situ anterior and posterior capsules of 35 eye-bank eyes (Group 1) donated by healthy men aged 20 to 40 years (mean 27.1 years) were measured with a biomembrane strength device. Sixteen eyes (Group 2), from donors aged 20 to 37 years (mean 27.0 years) and similar to those in Group 1, were measured in the same way after the anterior and posterior capsules were exposed to glucose 50% solution for 15 minutes. RESULTS: In Group 1, anterior and posterior capsule strength was 6.269 +/- 1.118 and 3.755 +/- 0.835 g, respectively (P < .01), and the correlation between the tensile strength of the anterior and posterior capsules was statistically significant (r = .94; P < .001). In Group 2, the strength of the capsules increased to 9.024 +/- 0.586 and 4.424 +/- 0.761 g, respectively, a finding that was statistically significantly different from that in Group 1 (P < .01 and .05, respectively. CONCLUSION: The tensile strength of the anterior capsule was stronger than that of the posterior capsule under the experimental conditions. Glucose 50% solution has the potential to increase the tensile strength of anterior and posterior capsules.

Adult↗

PubMed2004

Self-assembled polymer membrane capsules inflated by osmotic pressure.

We fabricate and characterize capsules that are composite membranes, made of a polymer network stabilized by adsorption to colloids and inflated by osmotic pressure from internal free polyelectrolyte; here, poly-l-lysine forms the network and inflates the capsules. To assess these capsules' properties and structure, we deform capsules using microcantilevers and use finite element modeling to describe these deformations. Additional experimental tests confirm the model's validity. These capsules' resilient response to mechanical forces indicates that loading and shear should be good triggers for the release of contents via deformation. The osmotic pressure inflating these capsules has the potential to trigger release of contents via deflation in response to changes in the capsules' environment; we demonstrate addition of salt as a trigger for deflating capsules. Because these capsules have a variety of release triggers available and the technique used to fabricate them is very flexible and allows high encapsulation efficiency, these capsules have very high potential for application in many areas.

Capsules↗

PubMed1997

Chitosan capsules for colon-specific drug delivery: improvement of insulin absorption from the rat colon.

The objective of this study was to estimate colon-specific insulin delivery with chitosan capsules. In vitro drug release experiments from chitosan capsules containing 5(6)-carboxyfluorescein (CF) were carried out by the Japan Pharmacopoeia (J. P.) rotating basket method with some slight modifications. The intestinal absorption of insulin was evaluated by measuring the plasma insulin levels and its hypoglycemic effects after oral administration of the chitosan capsules containing insulin and additives. Little release of CF from the capsules was observed in liquid 1, an artificial gastric juice (pH 1), or in liquid 2, an artificial intestinal juice (pH 7). However, the release of CF was markedly increased in the presence of rat cecal contents. A marked absorption of insulin and a corresponding decrease in plasma glucose levels was observed following the oral administration of these capsules that contain 20 IU of insulin and sodium glycocholate (PA% = 3.49%), as compared with the capsules containing only lactose or only 20 IU of insulin (PA% = 1.62%). The hypoglycemic effect started from 8 h after the administration of chitosan capsules when the capsules entered the colon, as evaluated by the transit time experiments with chitosan capsules. These findings suggest that chitosan capsules may be useful carriers for the colon-specific delivery of peptides including insulin.

Animals↗

PubMed2005

A novel diagnostic tool for detecting functional patency of the small bowel: the Given patency capsule.

BACKGROUND AND STUDY AIMS: The current visualization of small-bowel strictures using traditional radiological methods is associated with high radiation doses and false-negative results. These methods do not always reveal small-bowel patency for solids. The aim is to assess the safety of the Given patency system and its ability to detect intestinal strictures in patients with strictures that are known or suspected radiologically. MATERIALS AND METHODS: The Given patency capsule is composed of lactose, remains intact in the gastrointestinal tract for 40-100 hours post ingestion, and disintegrates thereafter. A total of 34 patients with small-bowel stricture were prospectively enrolled; 30 had a previous diagnosis of Crohn's disease, three had adhesion syndrome and in one ischemic enteritis was suspected. Of the patients, 15 (44.1 %) had previously undergone surgery. Following ingestion, the capsule was monitored for integrity and transit time, using a specially designed Given scanner and also radiologically. Seventeen patients had been enrolled with the intent of using the patency capsule as a preliminary test in patients with small-bowel strictures before undergoing video capsule endoscopy. RESULTS: 30 patients (88.2 %) retrieved the capsule in the stool; it was intact in 20 (median transit time 22 hours), and disintegrated in 10 patients (median transit time 53 hours). Six patients complained of abdominal pain which disappeared within 24 hours. The scanner successfully indicated the presence of the capsule in 94 % of cases. Ten patients underwent video capsule endoscopy following the patency capsule examination; in all of these the video capsule passed through the small-bowel stricture. CONCLUSIONS: This feasibility study has shown that the Given patency capsule is a safe, effective, and convenient tool for assessment of functional patency of the small bowel. It can indicate functional patency even in cases where traditional radiology indicates stricture.

Adult↗

PubMed2007

Hard gelatin and hypromellose (HPMC) capsules: estimation of rupture time by real-time dissolution spectroscopy.

The objective of this study was to measure rupture time of gelatin and hypromellose (hydroxypropyl methylcellulose or HPMC) capsules using a novel approach based on real-time dissolution spectroscopy. Rupture time was measured in standard dissolution apparatus at a constant temperature using a dip-type fiber-optic probe. Labrasol released from the capsules was treated as the marker of the rupture process. Light scatter generated by the emulsified labrasol was detected by an ultrafast monochromator at scan rates approximating 24,000 nm/min. This technique was validated by measuring the dissolution time of gelatin capsules. Rupture times of hypromellose capsules were studied as a function of capsule size, capsule grade, and dissolution medium. Statistical correlations were analyzed by ANOVA. Rupture time of hypromellose capsules was dependent on both the medium and the grade of the capsule, and was independent of capsule size. The composition of the dissolution medium contributes to the rupture time of the capsules and should be considered when fast release and quick biological response is desired. Release delay, however, may not manifest itself in vivo and the time to maximum plasma concentration may not be significant.

Capsules↗

PubMed2003

Semisolid matrix filled capsules: an approach to improve dissolution stability of phenytoin sodium formulation.

Seven semisolid fill bases were selected for the formulation of 24 capsule formulations, each containing 100 mg of phenytoin sodium. The fill materials were selected based on the water absorption capacity of their mixtures with phenytoin sodium. The fill matrices included lipophilic bases (castor oil, soya oil, and Gelucire (G) 33/01), amphiphilic bases (G 44/14 and Suppocire BP), and water-soluble bases (PEG 4000 and PEG 6000). The drug:base ratio was 1:2. Excipients such as lecithin, docusate sodium, and poloxamer 188 were added to some formulations. The dissolution rate study indicated that formulations containing lipophilic and amphiphilic bases showed the best release profiles. These are F4 (castor oil-1% docusate sodium); F10 (castor oil-3% poloxamer 188); F14 (G33/01-10% lecithin); F17 (G33/01-1% docusate sodium), and F20 (Suppocire BP). Further, the dissolution stability of the five formulations above was assessed by an accelerated stability study at 30 degrees C and 75% RH using standard Epanutin capsules for comparison. The study included the test and standard capsules either packed in the container of marketed Epanutin capsules (packed) or removed from their outer pack (unpacked). Release data indicated superior release rates of castor oil based formulations (F4 and F10) relative to standard capsules in both the unpacked and packed forms. For instance, the extent of drug release at 30 min after 1 month was 91% for F4 and F10 and 20% for standard capsules. Drug release from packed capsules after 6 months storage was 88% for both formulations F4 and F10 and 35% for standard capsules. In conclusion, the pharmaceutical quality of phenytoin sodium capsules can be improved by using a semisolid lipophilic matrix filled in hard gelatin capsules.

Alkalies↗

PubMed1992

Type b capsule inhibits ingestion of Haemophilus influenzae by murine macrophages: studies with isogenic encapsulated and unencapsulated strains.

Phagocytosis may be important in clearing Haemophilus influenzae from the bloodstream. To define the effect of type b capsule on phagocytosis, binding and ingestion by macrophages was measured for 5 isogenic sets of capsule-sufficient strains (clinical isolates and type b transformants of capsule-deficient mutants) and capsule-deficient mutants (strains lacking a 9-kb EcoRI fragment of chromosomal DNA associated with type b capsule expression). Capsule-sufficient strains were not bound in the absence of serum, whereas capsule-deficient strains were bound and ingested (1.8-5.1 organisms/macrophage; 59%-97% ingested). In the presence of nonimmune serum, capsule-sufficient strains were largely bound but not ingested (4.7-7.2 organisms/macrophage; 7%-21% ingested), whereas capsule-deficient strains were nearly all ingested (6.2-10.5 organisms/macrophage; 93%-97% ingested). Strains resisting ingestion caused persistent bacteremia 24 h after intravenous challenge in mice and were more likely than readily ingested strains to cause persistent bacteremia or death in infant rats. Thus, type b capsule inhibits ingestion by macrophages; resistance to ingestion may be an important virulence determinant of type b organisms.

Agglutination Tests↗

PubMed2004

A novel diagnostic tool for detecting oesophageal pathology: the PillCam oesophageal video capsule.

BACKGROUND: Gastro-oesophageal reflux disease is a common entity. Erosive oesophagitis, ulcers and Barrett's oesophagus, which is found in up to 10% of gastro-oesophageal reflux disease patients, characterize severe gastro-oesophageal reflux disease. Patients with Barrett's oesophagus have 0.5% per patient-year risk of developing oesophageal adenocarcinoma. Currently, it appears that a minority of those at risk for Barrett's oesophagus undergo screening in part because of the costs associated with endoscopy as well as risks of sedation. A new ingestible PillCam oesophageal capsule developed may offer an alternative office-based approach to visualize the oesophagus without sedation. AIM: To compare the oesophageal capsule to conventional upper endoscopy for detection of oesophageal pathologies. METHODS: A newly developed capsule, which acquires video images from both ends of the device at a 4 frame/s rate, was ingested by 17 fasting patients with suspected oesophageal disorders. An ingestion procedure aimed to lengthen capsule transit time in the oesophagus was utilized. Subsequently, a standard upper endoscopy was carried out. The investigator interpreting the capsule findings was blinded to the endoscopy results and vice versa. Patients with dysphagia, known Zenker's diverticulum, intestinal obstruction, cardiac pacemaker or pregnancy were excluded. RESULTS: Twelve of the 17 patients examined had oesophageal findings using the endoscope as the gold standard. Capsule endoscopy identified oesophageal pathology in all 12 of these patients and an additional pathology in one patient that was missed during endoscopy. For the purpose of this study, this finding was regarded as a false-positive. The mean oesophageal passage time was 189 +/- 280 s. The positive predictive value of the oesophageal capsule for any oesophageal pathology was 92% and the negative predictive value was 100%. Oesophageal capsule sensitivity was 100% and specificity 80%. There were neither swallowing difficulties nor complications subsequent to ingestion in any subjects. Seventy-three percentage of patients preferred the oesophageal capsule procedure on conventional endoscopy. Only one patient preferred oesophagogastroduodenoscopy. CONCLUSIONS: This pilot study has shown that oesophageal capsule endoscopy is an accurate, convenient, safe and well-tolerated method to screen patients for significant oesophageal disorders. No sedation is required, which may allow simple, office-based screening and assessment. Further, large-scale studies are necessary to more fully assess this novel diagnostic tool.

Adult↗

PubMed2005

Critical determinants of the interactions of capsule-expressing Neisseria meningitidis with host cells: the role of receptor density in increased cellular targeting via the outer membrane Opa proteins.

Neisseria meningitidis capsule is an important virulence determinant required for survival in the blood but is reportedly involved in inhibiting cellular interactions mediated by meningococcal outer membrane adhesins. However, evidence from our previous studies suggested that target receptor density on host cells may determine whether or not capsulate bacteria can adhere via outer membrane proteins such as Opa. To confirm this and evaluate the impact of capsulation on bacterial interactions, we used Opa(+) and Opa(-) derivatives of capsulate and acapsulate meningococcal isolates and transfected cell lines expressing CEACAM1, a receptor targeted by Opa proteins. To assess the extent and rate of cell association, subpopulations of stably transfected Chinese hamster ovary cells with different receptor levels were derived. A quantitative correlation of CEACAM1 levels and Opa-dependent binding of both capsulate and acapsulate bacteria was demonstrated, which was accelerated at high receptor densities. However, it appears that invasion by Opa(+) capsulate bacteria only occurs when a threshold level of CEACAM density has been reached. Target cells expressing high levels of CEACAM1 (MFI c. 400) bound threefold more, but internalized 20-fold more Opa(+) capsulate bacteria than those with intermediate expression (MFI c. 100). No overall selection of acapsulate phenotype was observed in the internalized population. These observations confirm that capsule may not be an adequate barrier for cellular interactions and demonstrate the role of a host factor that may determine capsulate bacterial invasion potential. Upregulation of CEACAMs, which can occur in response to inflammatory cytokines, could lead to translocation of a small number of fully capsulate bacteria across mucosal epithelium into the bloodstream sufficient to cause a rapid onset of disseminated disease. Thus the data also suggest a novel rationale for the epidemiological observations that individuals with prior infectious/inflammatory conditions carry a high risk of invasive meningococcal disease.

Animals↗

PubMed1995

Development of a colon delivery capsule and the pharmacological activity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in beagle dogs.

A peroral dosage form was examined to deliver recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the colon in beagle dogs. A new gelatin capsule with its inside surface coated with ethylcellulose was prepared for this purpose. RhG-CSF was dissolved with propylene glycol and was filled in the capsule. Several kinds of ethylcellulose-gelatin capsules with an ethylcellulose layer of thickness 46 to 221 mm were used. The capsule was filled with propylene glycol solution containing fluorescein as an absorption marker, castor oil derivative and citric acid. The hardness of the capsule was tested after the gelatin layer was dissolved using a hardness tester and was dependent on the thickness of the ethylcellulose layer of the capsule. The time, Tmax, at which plasma fluorescein level reaches its maximum following oral administration of ethylcellulose capsules was used as a parameter for the in-vivo disintegration time of the ethylcellulose capsule into the colon. Capsules of thickness 84 mm with a Tmax of 4-6 h were filled with rhG-CSF solution containing fluorescein and were administered to dogs. After administration, blood samples were collected for 96 h and the blood total leucocyte (BTL) counts were measured as a pharmacological index of rhG-CSF. The maximum BTL count appeared at 10 h then gradually decreased and returned to its normal level at 48 h. These results suggest the usefulness of ethylcellulose capsules for the delivery of rhG-CSF to the colon and the possibility of a new oral rhG-CSF dosage form has been elucidated.

Animals↗

PubMed2006

Analysis of the polysaccharide capsule of the systemic pathogen Streptococcus iniae and its implications in virulence.

Systemic pathogens have developed numerous strategies for evading the defenses of the host, permitting dissemination and multiplication in various tissues. One means of survival in the host, particularly in the bloodstream, has been attributed to the ability to avoid phagocytosis via capsular polysaccharide. To further define the virulence capacity of Streptococcus iniae, a zoonotic pathogen with the ability to cause severe systemic disease in both fish and humans, we performed an analysis of the capsule locus. The initial analysis included cloning and sequencing of the capsule synthesis operon, which revealed an approximately 21-kb region that is highly homologous to capsule operons of other streptococci. A genetic comparison of S. iniae virulent strain 9117 and commensal strain 9066 revealed that the commensal strain does not have the central region of the capsule operon composed of several important capsule synthesis genes. Four 9117 insertion or deletion mutants with mutations in the beginning, middle, or end of the capsule locus were analyzed to determine their capsule production and virulence. Virulence profiles were analyzed for each mutant using three separate criteria, which demonstrated the attenuation of each mutant in several tissue environments. These analyses also provided insight into the different responses of the host to each mutant strain compared to a wild-type infection. Our results demonstrate that capsule is not required for all host environments, while excess capsule is also not optimal, suggesting that for an "ideal" systemic infection, capsule production is most likely regulated while the bacterium is in different environments of the host.

Animals↗

PubMed1999

Consequences of reduction of Klebsiella pneumoniae capsule expression on interactions of this bacterium with epithelial cells.

Most Klebsiella pneumoniae clinical isolates are fully encapsulated and adhere in vitro to intestinal cell lines with an aggregative pattern. In this study, the influence of the capsule on interactions with epithelial cells was investigated by creating an isogenic mutant defective in the synthesis of the capsule. Determination of the uronic acid content of bacterial extracts confirmed that the mutant did not produce capsular polysaccharides whereas, with the wild-type strain, the level of encapsulation was growth phase dependent and reached a maximum during the lag and early log phases. Assays performed with different epithelial cell lines, Int-407, A-549, and HEp-2, showed that the capsule-defective mutant demonstrated greater adhesion than did the wild-type strain and that the aggregative pattern was maintained, indicating that the capsule was not related to the adhesion phenotype. In contrast, when the mucus-producing HT-29-MTX cells were used, the encapsulated wild-type strain adhered more strongly than did the capsule-defective mutant. No invasion properties were observed with any of the capsular phenotypes or cell lines used. The K. pneumoniae adhesin CF29K was detected by Western blot analysis and enzyme-linked immunosorbent assay on the surface of transconjugants obtained after transfer of a conjugative plasmid harboring the CF29K-encoding genes into both the wild-type and the capsule-defective strains. The amounts of adhesin detected were greater in the capsule-defective background strain than in the wild-type encapsulated strain and were associated with an increase in the level of adhesion to Caco-2 cells. Moreover, RNA slot blot experiments showed that transcription of the adhesin-encoding gene was markedly increased in the capsule-defective mutant compared to the wild-type encapsulated background. These results suggest (i) that the capsule plays an active role during the initial steps of the pathogenesis by interacting with mucus-producing cells but is subsequently not required for the adhesin-related interaction with the epithelial cell surface and (ii) that the expression of the adhesin is modulated by the presence of a capsule at a transcriptional level.

Bacterial Adhesion↗

PubMed2004

MMP inhibition prevents human lens epithelial cell migration and contraction of the lens capsule.

PURPOSE: The development of posterior capsule contraction following cataract surgery is caused by the activity of residual lens epithelial cells. Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes, which are essential for cell migration and cell mediated contraction following wound healing. The authors investigated whether inhibiting MMP activity can reduce lens epithelial cell migration and as a result, lead to a reduction in cell mediated capsule contraction. METHODS: Human donor lens capsules were cultured and treated with a broad spectrum MMP inhibitor, Ilomastat (GM6001). MMP-2 and MMP-9 production were determined by ELISA. Cell migration onto the posterior capsule and capsule contraction were digitally measured. RESULTS: MMP inhibition significantly reduced lens epithelial cell migration onto the posterior capsule (p<0.05), and a reduction in capsule contraction was observed (p<0.05). CONCLUSIONS: Ilomastat significantly reduced lens epithelial cell migration onto the posterior capsule surface and inhibited capsule contraction. MMP inhibition may have a role in the therapeutic treatment of posterior capsule opacification.

Cataract Extraction↗

PubMed1981

A subcutaneous capsule for long-term studies.

In assessing interstitial fluid dynamics, perforated capsules have a limited existence because of the ingrowth of connective tissue. A permanently patent capsule (1 yr) can be obtained by implanting 1.9-cm lengths of Tygon tubing (OD 7.9 mm, ID 4.8 mm). After implant, the capsule is invested in connective tissue, and a thin strand of connective tissue invades both ends of the capsule. In 2-3 wk, the connective tissue joins in the capsule and there is no further ingrowth of connective tissue. This tissue bridge through the center of the capsule is richly vascularized, eventually containing small central arteries and veins. Protein content of capsule fluid was 50-60% of plasma, with albumin proportionately higher in the capsule. Intracapsule pressures averaged -2.08 mmHg. Communication between capsule contents and vascular volume appeared to be size-dependent in that the [35S]sulfate and [3H]inulin count could be measured in tail blood 5 min after intracapsule injection and it increased over 30 min. This did not occur with [14C]dextran (mol wt 70,000) and [14C]globulins (mol wt 150,000). This capsule appears to lend itself to long-term studies related to interstitial fluid dynamics and/or capillary exchange.

Animals↗

PubMed2005

Noncontact optical measurement of lens capsule thickness in human, monkey, and rabbit postmortem eyes.

PURPOSE: To measure interspecies thickness differences in the central anterior and posterior capsules of postmortem crystalline lenses, by a technique that maintains the anatomic integrity of the lens. METHODS: Central capsule thickness was measured with a custom-built, noncontact optical system, using a focus detection technique. Anterior and posterior lens capsule thickness measurements were performed on 22 human, 29 monkey, and 34 New Zealand White rabbit intact postmortem lenses in situ. Eyes were prepared for optical measurements by bonding a PMMA ring to the sclera in the region of the ciliary body after the conjunctiva, adipose, and muscle tissues were removed. The posterior pole was removed by making a circumferential incision through the sclera approximately 7 mm posterior to the limbus. Excess vitreous was removed to expose the posterior capsule surface, and the eye assembly was placed on a Teflon slide. The cornea and iris were sectioned to expose the anterior capsule surface. After the experiments, the lenses were excised, placed in 10% buffered formalin, and prepared for histology. Lens capsule thickness was measured from the histologic slides and compared to the optical RESULTS: results. Central anterior lens capsule thickness was 8.2 +/- 5.5 (human), 7.5 +/- 4.4 (monkey), and 10.7 +/- 4.2 (rabbit) microm optically and 12.4 +/- 2.5 (human), 10.7 +/- 3.7 (monkey), and 10.4 +/- 2.0 (rabbit) microm histologically. Central posterior capsule thickness was 6.3 +/- 2.2 (human), 5.9 +/- 1.7 (monkey), and 7.8 +/- 2.3 (rabbit) microm optically and 4.1 +/- 1.5 (human), 3.5 +/- 1.6 (monkey), and 4.7 +/- 2.5 (rabbit) microm histologically. CONCLUSIONS: The central anterior and posterior lens capsule thicknesses do not appear to vary considerably among human, rabbit, and monkey eyes. There were significant differences between optical in situ measurements and histology, which indicates that histologic preparation may affect lens capsule thickness.

Adult↗

PubMed1992

Bioavailability and patient acceptance of cyclosporine soft gelatin capsules in renal allograft recipients.

OBJECTIVE: To evaluate the relative bioavailability and patient acceptance of cyclosporine (CSA) soft gelatin capsule versus oral solution in renal allograft recipients. DESIGN, SETTING, AND PATIENTS: The bioavailability of CSA capsules was compared with that of CSA solution with crossover study design in the outpatient clinic setting. Nine renal allograft recipients with stable renal function participated in this study. METHODS: CSA dose was switched from solution to capsule in each patient for seven days. At steady-state, nine blood samples were obtained over a 12-hour period from each patient on day 7 for CSA solution and on day 14 for CSA capsules. CSA blood samples were analyzed by HPLC and fluorescence polarization immunoassay (FPIA) methods. Time to peak concentration (Tmax), peak concentration (Cmax), and area under the curve (AUC) were calculated on days 7 and 14, and compared using the matched Student's t-test. Patient acceptance was evaluated by patient preference on the questionnaire. RESULTS: For CSA blood concentrations measured by HPLC assay, the Tmax, Cmax, and AUC were 3.4 +/- 1.3 h, 569 +/- 240 nmol/L, and 4659 +/- 2144 h.nmol/L (mean +/- SD), respectively, with solution and 4.2 +/- 2.1 h, 560 +/- 257 nmol/L, and 4765 +/- 1799 h.nmol/L (mean +/- SD), respectively, with capsules. These differences were not significant (p greater than 0.1). The bioavailability was not significantly different between capsules and solutions when it was measured by PFIA assay (p greater than 0.1). The mean (+/- SD) relative bioavailability of capsules compared with solution was 109 +/- 29 percent AUC (0-12 h) measured by HPLC and 111 +/- 27 percent AUC (0-12 h) measured by FPIA. All patients expressed preference for capsules over the solution. CONCLUSIONS: CSA oral soft gelatin capsule is bioequivalent to CSA oral solution and most patients preferred the capsule to the oral solution.

Administration, Oral↗

PubMed1989

Reinforcing effects of caffeine in coffee and capsules.

In a residential research ward the reinforcing and subjective effects of caffeine were studied under double-blind conditions in volunteer subjects with histories of heavy coffee drinking. In Experiment 1, 6 subjects had 13 opportunities each day to self-administer either a caffeine (100 mg) or a placebo capsule for periods of 14 to 61 days. All subjects developed a clear preference for caffeine, with intake of caffeine becoming relatively stable after preference had been attained. Preference for caffeine was demonstrated whether or not preference testing was preceded by a period of 10 to 37 days of caffeine abstinence, suggesting that a recent history of heavy caffeine intake (tolerance/dependence) was not a necessary condition for caffeine to function as a reinforcer. In Experiment 2, 6 subjects had 10 opportunities each day to self-administer a cup of coffee or (on different days) a capsule, dependent upon completing a work requirement that progressively increased and then decreased over days. Each day, one of four conditions was studied: caffeinated coffee (100 mg/cup), decaffeinated coffee, caffeine capsules (100 mg/capsule), or placebo capsules. Caffeinated coffee maintained the most self-administration, significantly higher than decaffeinated coffee and placebo capsules but not different from caffeine capsules. Both decaffeinated coffee and caffeine capsules were significantly higher than placebo capsules but not different from each other. In both experiments, subject ratings of "linking" of coffee or capsules covaried with the self-administration measures. These experiments provide the clearest demonstrations to date of the reinforcing effects of caffeine in capsules and in coffee.

Adult↗

PubMed1998

Factors affecting zero-order release kinetics of porous gelatin capsules.

Porous gelatin capsules were prepared by entrapping gas bubbles or by drilling in the capsule wall with syringe needles. After hardening by formaldehyde, the capsules were supposed to provide a floating sustained release over 10 hr. Different pore sizes, pore numbers, pore orientational symmetry on the capsule wall, the amount of the effervescent material added to prepare the capsule, the exposure time to formaldehyde, and excipient selected were studied to evaluate their influences on the dissolution kinetics. The gelatin capsules were prepared by adding various amounts of effervescent material or by drilling in the capsule wall with a syringe and then hardening by formaldehyde. Verapamil was used as the model drug and starch or lactose was the only excipient. Verapamil and excipient were mixed and used to fill the prepared capsule. The release of verapamil from the capsules follows the zero-order drug release and was observed after the burst phase. The porous capsule, when filled with the mixture of active ingredients and excipient, can achieve a zero-order release system.

Capsules↗