Sustained-release Medication Research Articles

Future approaches to glaucoma management

AbstractThere have been several advances in glaucoma management over the past few years. This talk will include coverage of medical changes such as neuroprotective strategies and sustained release medications, and diagnostic advances including artificial intelligence applications, the water drinking test, DARC, visual field analysis and tear fluid assessment. Finally, home monitoring possibilities in glaucoma including self‐tonometry and visual field testing will be discussed.

S2279 Bisphosphonate-Induced Esophageal Stricture: A Situation of Unusual Severity

Introduction: Pill-induced esophageal stricture is a rare but well-documented condition associated with various causative agents. Potassium chloride and quinine are the most common causes and are more likely to produce stricture than other agents (such as Bisphosphonates and Tetracyclines). Predisposing factors include older age, male gender, sustained release medication formulation and prior esophageal structural abnormality. Case Description/Methods: An 80-year-old female with history of osteoporosis taking Alendronate presented with 3 weeks history of progressive solid and liquid dysphagia and endorsed 20 lbs weight loss. The patient reported inability to keep any food down for 3 days prior to presentation and had begun requiring the use of oral suction at bedside due to inability to swallow her own saliva. She appeared clinically stable on exam. He laboratory study showed profound electrolytes abnormality. Esophagogastroduodenoscopy (EGD) showed circumferential mid esophageal ulceration that progressed to a narrow stricture that could not be traversed even with a stricture scope (5.9 mm diameter). Alendronate was discontinued and the patient was treated with liquid formulation omeprazole twice daily. Her diet was slowly advanced from clear liquid to mince. Her hospitalization was prolonged because she developed refeeding syndrome after reinitiating her diet. She was discharged after her electrolytes normalized. Two months after her initial presentation, her dysphagia had completely resolved. A repeat EGD revealed a tapered benign-appearing stricture in the distal esophagus, which was traversed without resistance with a standard gastroscope. Balloon dilation was performed to a diameter of 13 mm without creation of a mucosal rent (Figure). Discussion: This case highlights the severity and potential rapid progression of pill-induced esophageal damage caused by Bisphosphonate therapy. Esophagitis or esophageal mucosa ulceration are common. The mucosal damage is caused by direct contact of the drug with the esophageal mucosa. Reports of stricture formation from Alendronate use are rare. Stricture formation may be caused by chronic inflammation from long-term use. Clinicians should have a low index suspicion in a high-risk patient presenting with classic symptoms of dysphagia. In addition, patients should receive counseling on proper pill ingestion technique to prevent potential damage.Figure 1.: See attachment.

Medication-administration-via-enteral-feeding-tubes-a-survey-of-nurses-knowledge-and-practice

Introduction: Enteral feeding is a type of nutritional support for critically ill patients who are unable to tolerate oral feeding. It is vital to ensure that nurses practise proper administration techniques via enteral feeding tubes (EFT) to ensure that medications can be delivered safely and effectively. Objective: This study aims to assess the knowledge and practice of nurses on medication administration through EFT. The association between demographics and knowledge was also explored. Method: This study is a cross-sectional, self-administered, content-validated, pre-tested questionnaire survey involving all nurses who worked in the ward setting at Hospital Queen Elizabeth II from August to December 2020. Result: A total of 409 questionnaires were sent out with 252 responses received. The majority of respondents were female (n = 240, 95.6%) with a median working experience of 84 months (interquartile range of 44 months). Most nurses knew that the immediate-release dosage forms (n = 237, 94.4%) may be crushed and administered through EFT. Similarly, most nurses were aware that sublingual nitroglycerin (GTN) tablets should not be crushed (n = 232, 92.8%) and that nystatin suspension should not be administered via EFT (n = 212, 85.1%). However, about half of the nurses responded incorrectly when questioned about the particulars of EFT involving the administration of sustained-release medications (n = 152, 60.6%), soft gelatin capsules (n = 111, 44.4%) and hard gelatin capsules (n = 102, 40.6%). Meanwhile, in terms of practice, a majority of the nurses would correctly routinely flush the EFT before (n = 226, 90.4%) and after (n = 245, 98.8%) the administration of medications. However, only a small proportion of nurses (n = 43, 17.3%) demonstrated the appropriate practice of administering all medications separately all the time. Furthermore, it was also worth noting that for some specific knowledge-based questions, nurses from the intensive care setting had more correct responses when compared to those from the general ward setting (p < 0.05). Conclusion: The knowledge gap and inconsistencies in practices amongst nurses related to the use of EFT may lead to suboptimal delivery of medications, whilst potentially compromising patient outcomes. Hence, continuous educational programs should be carried out to ensure safe and effective drug administration through EFT.

Prospects of MMX Mesalazine in Routine Outpatient Treatment of Ulcerative Colitis

Aim. A general review of treatment approaches to ulcerative colitis (UC) and the importance of oral 5-aminosalicylic acid (5-ASA) for its routine outpatient management.Key points. The choice of drug therapy for UC remission induction and maintenance is linked to the intestinal lesion extent and disease attack severity. The 5-ASA therapy remains the mainstay UC treatment in routine outpatient practice, with prescription rate of 80–90%. Oral 5-ASA drugs are often used in monotherapy or when oral and rectal 5-ASAs are recommended in combination. As a sustained-release medication, the MMX mesalazine multi-matrix delivery system provides for higher active substance dosages along entire colonic mucosa, including its distal portions. A higher active substance dosage per tablet reduces the number of intakes and ensures a better patient adherence, both in terms of daily and long-term therapy.Conclusion. The 5-ASA drugs are most commonly prescribed in outpatient practice. Sustained-release 5-ASAs provide for a more effective active ingredient distribution at higher dosages along colonic mucosa.

Concerns regarding tablet splitting: a systematic review.

Tablet splitting can provide dose flexibility and cost savings; however, pharmaceutical representatives typically discourage the practice. To identify and summarise all published concerns related to tablet splitting and to present the experimental evidence that investigates those concerns. Systematic review and qualitative synthesis of tablet-splitting concerns and evidence. Medline and EMBASE databases were searched over all years of publication for articles in English discussing the splitting of tablets. Eligible articles included original research, narrative reviews, systematic reviews, and expert opinion. After removing duplicates, 1837 potentially relevant articles underwent dual review, whereupon 1612 articles were excluded based on title and abstract. After examination of 225 full texts, 138 articles were included (one systematic review, four narrative reviews, 101 original research articles, and 32 opinion articles). The described concerns included difficulty breaking tablets, loss of mass, weight variability, chemical instability, overly rapid dosing if sustained-release medications are split, non-compliance, and patient confusion resulting in medication errors. No substantive evidence was found to support concerns regarding loss of mass, weight variability, chemical instability, or non-compliance. Evidence does support some older adults struggling to split tablets without tablet splitters, and the inappropriateness of splitting sustained-release preparations, given the potential for alteration of the rate of drug release for some products. With the exception of sustained-release tablets, which should not be split, and excepting those older people who may struggle to split tablets based on physical limitations, there is little evidence to support tablet-splitting concerns.

Lignin-Based Hollow Nanoparticles for Controlled Drug Delivery: Grafting Preparation Using β-Cyclodextrin/Enzymatic-Hydrolysis Lignin.

Due to its abundance, degradability, and low toxicity, lignin is a promising raw material for the preparation of nanomaterials. However, efficient encapsulation using lignin-nanomaterial for sustained-release medications remains a challenge. This study involves grafting β-cyclodextrin (β-CD), with a hollow toroidal structure, onto the enzymatic-hydrolysis lignin (EHL) to form CD-EHL. The modified lignin was next used to prepare hollow nanoparticles (LHNPs) via self-assembly to encapsulate the antitumor drug hydroxycamptothecin (HCPT). The results indicated that β-CD improved the network structure of modified lignin molecules. Moreover, LHNPs that self-assembled using CD-EHL had an increased specific surface area and greater porosity, and exhibited a spherical hollow structure and stability in phosphate-buffered saline. The drug loading and encapsulation efficiency of HCPT were 70.6 ± 9% and 22.02 ± 2%, respectively. An in vitro study showed that lignin-based nanoparticles have low toxicity, and the modified LHNPs demonstrated a good sustained-release capability. This study broadened the potential application of lignin as a renewable biomass material.

PSS63 - IDENTIFYING PATIENT PREFERENCES FOR GLAUCOMA TREATMENT: EVIDENCE FROM LITERATURE REVIEW

One of the main objectives of glaucoma treatment is to lower intraocular pressure through topical medication, laser, or more invasive procedures (surgery, or surgical implants). In addition, long-lasting drug depots may also soon be a treatment option. The aim of current review was to identify the patient preferences towards glaucoma treatment and relevant influencing factors. A comprehensive literature search was performed for studies published in English from inception through August 2017 in Embase, MEDLINE, MEDLINE-In Process, and Cochrane library. Studies reporting patient preferences for any glaucoma treatment were included. The review identified 32 studies (7 RCTs, 1 non-RCTs, 12 observational studies and 7 single-arm studies) including studies assessing treatment-switching (n=11) and factors influencing treatment preference (n=5). Patients receiving monotherapies had significantly higher treatment satisfaction compared to polytherapies (p=0.05). Topical agents (QD regimen) were more convenient compared to BID regimens (p=0.104). Among monotherapies, brimonidine was preferred over topical β-blockers (less efficacious) or dual therapies (less convenient); travoprost BAK-free over latanoprost; and bimatoprost over travoprost. Patients switching from PGA monotherapies or mono/adjunctive therapies were significantly more likely to accept fixed-dose combinations such as travoprost/timolol. Additionally, studies reported high patient willingness to accept a novel glaucoma treatment such as sustained drug delivery (via punctal plug, subconjunctival or intracameral route) and implant (p=0.011) based upon effectiveness and cost. Other factors influencing patient preference were clear center vision, outdoor mobility, travelling distance during follow-ups, and treatment-associated symptoms (vision blurring, drowsiness, or inhibition of sexual performance). No studies assessing surgical treatment options were identified. Evidence clearly indicates that glaucoma patients have preference towards more efficacious and less frequent medication regimens. In addition, patients are willing to accept novel treatment options such as surgical implants and sustained release medication depots. However, scarce evidence necessitates the need for more research focusing on patient preferences towards surgical treatment options.

Intraocular pressure elevation in uveitis

Raised intraocular pressure in uveitis, either due to the disease itself or secondary to treatment with steroids, is one of the most common causes of secondary glaucoma in clinical practice. There are currently no standardized criteria for the diagnosis nor guidelines for the management of raised intraocular pressure in uveitis. Intraocular pressure elevation may be due to any combination of several mechanisms and, as a result, the prognosis differs from primary glaucomas. In addition, the management of ongoing inflammation without elevating the intraocular pressure remains a challenge. Ideally, new anti-inflammatory agents should have better anti-inflammatory properties with safer intraocular pressure profiles, while sustained release medications to lower intraocular pressure would improve patient compliance.

An Accidental “Pillipectomy”: Medications That May Appear as Polyps in Colonoscopy

Purpose: To report interesting polypectomy. Methods: A 44 year old male presented for outpatient colonoscopy for intermittent rectal bleeding. His medical history was positive for hypertension, hyperlipidemia and low back pain being treated with nifedipine XL, simvastatin, and ibuprofen as needed. The patient completed taking his bowel prep in the morning of procedure and took his medications 4 hours prior to colonoscopy. The colonoscopy revealed a 1 cm semi-pedunculated polyp in the transverse colon, which was removed with snare polypectomy and retrieved with a Roth net. Upon retrieval the specimen appeared unusual resulting in detailed examination of the specimen. It appeared to be orange-red in color, round solid and non fleshy with a small dot in the center on one side, and a reddish gel stalk which detached. The “pillyp” (pill appearing as a polyp) was thought to be a delayed release medication tablet, with medication released from the pill appearing as a stalk colonoscopically. The “pillyp” was presented to the patient who was unable to identify the medication. The pharmacy was consulted and it was identified as nifedipine XL. Results: The rate of drug absorption is dependent on its rate of dissolution in GI fluids. This is the basis of extended release or sustained release drug preparations. The drugs with shorter half life and longer desired effect are delivered in the gut by means of special drug delivery systems as a result their active ingredients are released slowly or in repeated small amounts over time - usually for a period of 8 hours or more. Laxatives, diarrhea, history of bowel resection and likely recent bowel prep speed up the passage through the digestive tract. As a result there is a risk of certain extended release tablets to be inadvertently lodged and in the colon and appear as “pillyps” if patients take them around the time of their bowel preparations. Extended release medications which may appear as polyps during colonoscopy (“pillyps”): Oxybutynin (Ditropan XL), Nifedipine (Procardia XL), Nicardipine (Caredene SR), Isradipine (DynaCirc CR), Nifedipine (Afeditab CR), Galantamine (Razadyne ER), Ropinorole (Requip XL), Etodolac (Lodine XL), Nifedipine ER, Paroxetine (Paxil CR), Nifedipine (Procardia XL), Verapamil (Isoptin SR), Carbodopa and Levodopa (Sinemet CR), Carbamazapine (Tegretol-XR), Diclofenac (Voltaren-XR), Buproprion (Wellbutrin SR). Conclusion: Certain sustained release medications may appear in colon as polyps due to effects of bowel preparation, resulting in accidental “pillipectomy” as presented in this case. This case identifies an additional reason for physicians performing colonoscopy to be aware of their patients' detailed medication histories prior to colonoscopy, in order to provide optimal patient care.

Development and evaluation of aceclofenac-loaded mucoadhesive microcapsules

Microencapsulation is an accepted process used to achieve controlled release and drug targeting for many years. Mucoadhesion has been a topic of interest in the design of drug delivery systems to prolong its intestinal residence time. Mucoadhesion facilitates the intimate contact of the dosage form with the underlying absorption surface for improved bioavailability of drugs. Aceclofenac is a newer nonsteroidal anti-inflammatory drug (NSAID) having short biological half-life of 4–4.3 h, and therefore a sustained release medication is required to get prolonged effect and to reduce fluctuations in drug plasma concentration levels. Aceclofenac microcapsules were prepared employing sodium alginate as the coat material in combination with some mucoadhesive polymers such as (hydroxypropyl methyl cellulose) HPMC, (sodium carboxymethyl cellulose) Sod. CMC, Carbopol and methyl cellulose (MC) (drug:SA:polymer at ratios 2:2:1, 2:3:1 and 2:4:1), following orifice-ionic gelation technique. Infrared (IR) spectroscopy, differential scanning calorimetry and X-ray diffraction studies proved the compositions were compatible, without any interaction between the drug and excipients. The prepared microcapsules were evaluated for various physical and release parameters. The resulted microcapsules were found to be discrete and spherical in scanning electron microscopy studies and free flowing in rheological studies. The size of microcapsules was found to be around 757.44 ± 5.201 μm to 814.46 ± 6.586 μm. The microencapsulation efficiency was found to be higher in HPMC than in Carbopol > MC > Sod. CMC containing formulations, but the swelling index was found to be higher in Sod. CMC formulations. The microcapsules with HPMC exhibited good mucoadhesive property in the in vitro wash-off test. In vitro drug release studies of aceclofenac microcapsules were carried out up to 24 h and they followed zero-order release kinetics with Super Case II mechanism. The drug release from the microcapsules was sustained over a prolonged period with greater retardation in drug:SA:HPMC (2:4:1) containing microcapsules and this proved to be the best formulation.

Surprisingly delayed escalation of severe verapamil poisoning

We present a case report of intoxication by a potentially lethal dose of sustained-release verapamil with delayed escalation of complications. The patient was hospitalized 1.5 h after an attempted suicide with a very high dose of verapamil sustained-release (7.2 g). On admission the plasma concentrations were extremely high (3600 ng/l). Heart rate and blood pressure declined slowly with a surprising sudden escalation on the third day coupled with hemodynamic collapse and loss of consciousness. Complete recovery was achieved in spite of 2 h of extreme hypotension. We outline the clinical course, a need for massive bowel irrigation in case of sustained-release medication, the timing of a temporary pacing and the effect of centralization of circulation even on invasively measured blood pressure.

An investigation into the swelling properties, dimensional changes, and gel layer evolution in chitosan tablets undergoing hydration

AbstractThe purpose of this research is to determine several characteristics of chitosan lactate in tablet form such as dimensional changes, gel evolution, swelling (liquid uptake), and erosion using an image analysis method. The examination of these characteristics will be helpful in the design of oral drug delivery systems with this polymer. It has been demonstrated that image analysis is a valuable technique, allowing the study of quantitative measurements of dimensional and core changes and gel evolution. The dimensional expansion changes of the chitosan lactate tablets were greater in water, and the crushing strength and the stirring effect affected these attributes to a limited extent. The fastest and greatest liquid uptake was observed in water, whereas the greatest erosion was observed in HCl. The thickness of the gel layer increased considerably with time up to the eighth hour, indicating the formation and development of a thick and durable gel, particularly in water. This is an essential characteristic for potential sustained drug release delivery. Consequently, this polymer appears to be a versatile material and a promising vehicle for the preparation of various oral sustained release medications and relevant devices. © 2009 Wiley Periodicals, Inc. Adv Polym Techn 28:32–39, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.20147

Safe Medication Swallowing in Dysphagia: A Collaborative Improvement Project

Episodes of choking during medication administration to patients with dysphagia prompted a chart audit and caregiver interview to identify system problems that allowed inappropriate drug administration to occur. Sixty elderly patients residing on two patient care areas in a 500-bed complex continuing care facility were studied. The audit explored the actual nursing medication administration methods and compared this to the information obtained from various communication tools including instructions that appeared on the medication administration record (MAR), the current diet order, the recommendations of the speech-language pathologist (SLP) and comments on the nursing care plan. The audit yielded a number of discrepancies between nursing actions and the instructions obtain from these sources. We proposed that changes to the process of communicating medication swallowing recommendations among team members would lead to greater patient safety. Major practice changes included the use of standardized language by the SLP when making recommendations, the writing of SLP recommendations in the doctor's orders, the inclusion of SLP recommendations on the MAR and the creation of a "dysphagia alert" on the pharmacy computer system. An educational intervention was conducted to implement process changes. Its effectiveness was evaluated using a pre- and post-test and a participant satisfaction survey. A post-implementation audit showed compliance with the practice change. In summary, process changes were implemented to improve compliance with SLP medication-related swallowing recommendations and to prevent the inadvertent prescribing, dispensing or crushing of sustained-release medications in patients with dysphagia.

Are One or Two Dangerous? Calcium Channel Blocker Exposure in Toddlers

Unintentional pediatric ingestions of calcium channel blockers are increasing in frequency due to increased use of this antihypertensive class. Potential toxic effects include severe refractory hypotension and death; however, the true toxicity of unintentional pediatric ingestions of 1–2 pills is poorly defined. A literature review was conducted to more closely determine toxic and lethal dosages of calcium channel blockers in the pediatric population under 6 years of age. Results indicate that, although most accidental pediatric ingestions are asymptomatic, a small number do result in cardiovascular instability or even death. The dihydropyridines, particularly nifedipine, and the phenylalkylamine verapamil are most often implicated in symptomatic ingestions. There are no adequate data to identify which children are predisposed to illness, or to determine cutoffs for toxic dosages. However, ingestions of only one pill have been documented to cause severe symptoms, including death. Thus, emergency evaluation to assess potential toxicity is necessary, and gastrointestinal decontamination and in-hospital observation of at least 6 h after toxic ingestion for regular release medications, and 12–24 h after toxic ingestion for sustained release medications is recommended for all cases of unintentional calcium channel blocker ingestion in children younger than 6 years of age.

The role of activated charcoal and gastric emptying in gastrointestinal decontamination: A state-of-the-art review

Gastrointestinal decontamination has been practiced for hundreds of years; however, only in the past few years have data emerged that demonstrate a clinical benefit in some patients. Because most potentially toxic ingestions involve agents that are not toxic in the quantity consumed, the exact circumstances in which decontamination is beneficial and which methods are most beneficial in those circumstances remain important topics of research. Maximum benefit from decontamination is expected in patients who present soon after the ingestion. Unfortunately, many overdose patients present at least 2 hours after taking a medication, when most of the toxin has been absorbed or has moved well into the intestine, beyond the expected reach of gastrointestinal decontamination. Decontamination probably does not contribute to the outcome of many such patients, especially those without symptoms. However, if absorption has been delayed or gastrointestinal motility has been slowed, activated charcoal may reduce the final amount absorbed. The use of activated charcoal in these cases may be beneficial and is associated with few complications. Therefore, administration of activated charcoal is recommended as soon as possible after emergency department presentation, unless the agent and quantity are known to be nontoxic, the agent is known not to adsorb to activated charcoal, or the delay has been so long that absorption is probably complete. The use of gastric emptying in addition to activated charcoal has generated intense debate. Several large comparative studies have failed to demonstrate a benefit of gastric emptying before activated charcoal. Because complications of such 2-step decontamination include a higher rate of intubation, aspiration, and ICU admission, gastric emptying in addition to activated charcoal cannot be considered the routine approach to patients. However, there are several infrequent circumstances in which the data are inadequate to accurately assess the potential benefit of gastric emptying in addition to activated charcoal: symptomatic patients presenting in the first hour after ingestion, symptomatic patients who have ingested agents that slow gastrointestinal motility, patients taking sustained release medications, and those taking massive or life-threatening amounts of medication. These circumstances represent only a small subset of ingestions. In the absence of convincing data about benefit or lack of benefit of gastric emptying for these patients, individual physicians must act on a personal valuation: Is it better to use a treatment that might have some benefit but definitely has some risk or not to use a treatment that has any risk unless there is proven benefit? [Bond GR. The role of activated charcoal and gastric emptying in gastrointestinal decontamination: a state-of-the-art review. Ann Emerg Med. March 2002;39:273-286.]

Administration of medications through enteral feeding catheters

Enteral feeding catheters are commonly used to administer both nutritional feedings and oral forms of medications. Obstruction of the catheters is a major concern. To study characteristics of obstruction of enteral feeding catheters in ICU patients and current knowledge and practices of ICU nurses of administering medications through such catheters. A postcard invitation to participate in this descriptive survey was mailed to a random sample of 12,069 members of the American Association of Critical-Care Nurses. The 52-item investigator-designed questionnaire was mailed to the 1700 critical care nurses who agreed to participate; 1167 (68.6%) returned completed survey questionnaires. Nurses estimated that 33.8% of their patients received 8.9 doses of medication per day through the enteral feeding catheter. The rate of obstruction of the tube by medications was 15.6%. Crushed medications contributed to obstruction, although liquid forms of the medications often were available. Nurses' primary source of knowledge about administering medications through enteral feeding catheters was clinical practice (56.9%) and consultation with peers (21.7%); only 19% had had inservice training on the topic. Written agency guidelines varied considerably, and 74% of nurses used two or more techniques that were contrary to recommendations. Factors significantly associated with lower rates of obstruction of enteral feeding catheters included (1) assistance from the pharmacy service to ensure liquid forms of medications, (2) nurses' attendance at a relevant seminar or inservice training program, and (3) not routinely crushing and administering enteric-coated or sustained-release medications through the enteral feeding catheter. Collaboration between nursing and pharmacy services to ensure delivery of liquid medications and avoid use of crushed medications may reduce the high rate of catheter obstruction due to medications. Research-based guidelines and a more formal dissemination of information to nurses are needed.

Method of evaluation of sustained release microsphere formulations using the open chemostat system

The sustained release of cephalexin (CPX) as the monohydrate and ciprofloxacin (CFX) as the hydrochloride from separate 100000 Mol. Wt poly( l-lactic acid) microspheres (250–425 gmm sieve size range) was evaluated in an open chemostat system. Drug concentrations in pH 7.4 phosphate buffer solution (PBS) reached peak levels which were sustained for different periods of time, depending on the flow rate of PBS at a constant volume of 120 ml in the chemostat. At 0.46 ml/min flow rate CPX microspheres (33% w/w loading) sustained CPX concentrations for approx. 90 min (solubility = 40 mg/ml at pH 7.4, 37° C) whereas CFX (solubility = 5 mg/ml) was sustained for at least 6 h. Increasing drug loading increased peak levels of either antibiotic but decreased the sustained period of CPX only. Decreasing microsphere size to 125–250 gmm increased CPX or CFX concentration levels and decreased the sustained period to about 45 min and 2 h, respectively. At higher doses, CFX was sustained at higher concentrations over the 6 h period. Decreasing the flow rate in the chemostat increased sustained levels of CFX while increasing the flow rate decreased sustained levels. Thus, the chemostat system is convenient for testing the sustained release of drugs as a function of formulation parameters and to obtain information about the optimum doses of sustained release medication for in vivo administration.

Why Sustained-Release Medications? Practical Considerations in the Management of Patients With Anxiety

Why Sustained-Release Medications? Practical Considerations in the Management of Patients With Anxiety

Stimulant Medication and Attention Deficit—Hyperactivity Disorder

Fifty-eight children receiving stimulant medication for attention deficit-hyperactivity disorder at referral clinics for learning disabilities at two teaching hospitals in Massachusetts were invited to participate in a study of their knowledge and attitudes. The 45 respondents and parents completed separate questionnaires concerning how they felt about receiving stimulant medication. Eighty-nine percent of the children felt that the medication was helpful and 78% liked or were indifferent to it despite a high rate (85%) of reported side effects. The five children (11%) who responded that they would stop taking stimulant medication if they could were more likely to perceive the medication as unhelpful and were receiving standard methylphenidate hydrochloride rather than a long-acting preparation. We conclude that children's perspectives on medication should be elicited directly and sustained-release medication may be more acceptable to children with attention deficit-hyperactivity disorder.

Novel divisible tablet designs for sustained release formulations

Novel divisible tablet designs have been developed, which minimize the formation of new surface area upon division and thereby provide a means of administering a portion of the sustained release dose without appreciably altering the rate of drug release. A U.S. patent has been issued, claiming these divisible tablets for fractional dosing of sustained release medications [1]. Basic design features include lateral grooves on the top and bottom tablet surfaces at each line of division, which may be of variable depth, and a tablet shape that produces deep transverse grooves on the side of the tablet. Tablet shape, as well as the depth and angle of the dividing grooves, may be varied depending on the number of divisions desired, tablet size, weight, mechanical strength, and other formulation considerations. Distinctive features of oval bi-dosage tablets, oval tri-dos-age tablets, and elliptical bi-dosage tablets are examined. Divisible oval bi-dosage sustained released 400 mg Motrin tablets were evaluated. Cleavage resulted in tablet segments containing half the dosage of the whole tablet (within <0.2%). An increase in surface area, upon division, of only 2.49% was observed. In vitro drug release rates for the Motrin half tablets were essentially equivalent to those of the whole tablets.