Controlled-release Preparation Research Articles

Formulation and in vitro Evaluation of Eudragit L100 piroxicam

AbstractThe aim of this study was to formulate and evaluate controlled release preparations of a water-insoluble drug using Copolymers synthesized from acrylic and methacrylic acidesters (Eudragit L 100) as the retardant material. Microspheres were prepared by solvent evaporation method using an alcohol / liquid paraffin system. Span60 was used as the droplet stabilizer. The prepared microspheres were characterized for their micromeritic properties and drug loading, as well as by differential scanning calorimetry. The in vitro release studies were performed first in pH1.2 and then pH 6.8, phosphate buffer. The prepared microspheres were yellow, and spherical in shape. The drugloaded microspheres showed 71-85% of entrapment and release was extended up to 7 h. The differential scanning calorimetry thermographs showed stable character of drug in the drug-loaded microspheres and revealed the absence of drug-polymer interactions. The best-fit release kinetics was achieved with Higuchi plot. The release of drug was influenced by the drug to polymer ratio and particle size that was found to be diffusion controlled.

Design and evaluation of ethyl cellulose based matrix tablets of ibuprofen with pH modulated release kinetics

Controlled release preparations have been reported to reduce the gastro irritant and ulcerogenic effects of non steroidal antiinflammatory drugs. In the present study, an attempt was made to develop matrix tablet-based controlled release formulations of ibuprofen, using ethyl cellulose as the rate-controlling polymer. In order to prevent initial release of the drug in the acidic environment of the stomach, cellulose acetate phthalate was incorporated in the matrix in varying amounts. It was found that with increasing the proportion of ethyl cellulose in the matrix, the drug release was extended for 14-16 h. Incorporation of cellulose acetate phthalate in ethyl cellulose matrix provided very low initial release of the drug in the first 2-3 h followed by enhanced release rate in alkaline medium owing to the high solubility of cellulose acetate phthalate at basic pH which led to creation of a porous matrix. It was concluded that combination of cellulose acetate phthalate with ethyl cellulose in the matrix base can be an effective means of developing a controlled release formulation of ibuprofen with very low initial release followed with controlled release up to 14-16 h.

Formulation and in vitro Evaluation of Eudragit® Microspheres of Stavudine

Purpose: The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of a highly water-soluble drug, stavudine, using Copolymers synthesized from acrylic and methacrylic acid esters (Eudragit RS 100 and RL 100) as the retardant material. . Methods: Microspheres were prepared by solvent evaporation method using an acetone / liquid paraffin system. Magnesium stearate was used as the droplet stabilizer and n-hexane was added to harden the microspheres. The prepared microspheres were characterized for their micromeritic properties and drug loading, as well by fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry, x-ray powder diffractometry and scanning electron microscopy. The in vitro release studies were performed in pH 6.8, phosphate buffer. Results: The prepared microspheres were white, free flowing and spherical in shape. The drug-loaded microspheres showed 67-91% of entrapment and release was extended upto 6 to 8 h. The infrared spectra and differential scanning calorimetry thermographs showed stable character of stavudine in the drug-loaded microspheres and revealed the absence of drug-polymer interactions. X-ray diffraction patterns showed that there was decrease in crystallinity of the drug. Scanning electron microscopy study revealed that the microspheres were spherical and porous in nature. Conclusion: The best-fit release kinetics was achieved with Higuchi plot followed by zero order and First order. The release of stavudine was influenced by the drug to polymer ratio and particle size & was found to be diffusion controlled. Keywords: Stavudine, Eudragit, microspheres, controlled release, polymethacrylate > Tropical Journal of Pharmaceutical Research Vol. 4 (1) 2005: pp. 369-375

Preparation and In-vitro Characterization of Tizanidine Controlled-Release Microcapsular Matrices

Oral microencapsulated controlled release preparations of tizanidine hydrochloride (TIZ) were prepared by modified solvent evaporation technique using different proportions of ethyl cellulose as the retardant material. The microcapsules (TIZ1, TIZ2 and TIZ3) were compressed in to tablets (T-TIZ1, T-TIZ2 and T-TIZ3) for oral delivery. The prepared microcapsules were white, free flowing and spherical in shape, with the particle size varying from 215.38 ± 11.52 to 227.36 ± 12.89 μm and shows good drug entrapment efficiency. The 60% of TI2 release from microcapsules were found to be 2.15 ± 0.6, 2.98 ± 0.6 and 4.55 ± 0.8 h respectively for formulation TIZ1, TIZ2 and TIZ3 while their tablets i.e., T-TIZ1, T-TIZ2 and T-TIZ3 releases in 7.49 ± 1.2, 8.69 ± 0.6 and 15.24 ± 0.3 h respectively indicating more extension of time in tablet than microcapsules. The mechanism of drug release from tizanidine hydrochloride microcapsules and their tablets were studied by using Higuchi and Korsmeyer-Peppas models. The r-value for TIZ1, TIZ2 and TIZ3 indicates diffusion controlled with first order kinetic. The value of exponent coefficient (n) for T-TIZ1, T-TIZ2 and T-TIZ3 were found to be 0.874, 0.902 and 0.913 indicating anamolous, case-Ⅱ and case-Ⅱ transport release mechanism respectively.

Improving Oral Medicine Administration in Patients with Swallowing Problems and Feeding Tubes

Correct administration of oral medicines in patients with swallowing problems and feeding tubes remains a challenge. To improve drug administration in patients with swallowing problems and feeding tubes in a 1600 bed tertiary referral center in the State of Qatar. A questionnaire was used to evaluate the knowledge and practice of nursing staff from 6 different intensive care units (ICU). Questions assessed the respondents' knowledge of the purpose of controlled-release (CR) preparations, codes used for CR medication, the consequences of crushing these preparations, and their interactions with enteral feeds and feeding tubes. Based on the results of the questionnaire, a 2 day training program was conducted for a core group of 34 staff nurses from all units (ICU and non-ICU) and 3 nursing instructors. Following the principle of "training the trainers," the core group and the nursing instructors would widen the scope of education by running programs in the future. Lecture sessions for pharmacy staff and a monitoring tool to evaluate the practice were also developed. Overall knowledge of CR codes increased from 0% to 40%, correct crushing of solid preparations from 35% to 90%, and knowledge of possible interactions with the enteral feed or feeding tubes from 51% to 88%. Correct administration of medication in patients with feeding tubes improved from 32% to 83%. The quality and value of the 2 day training course received a mean score of 96%. While most nurses were aware of the purpose of CR formulations, little was known about the different codes used by drug companies and the consequences of crushing these preparations. Interactions with enteral feeds and feeding tubes were mostly overlooked. A 2 day training course followed by continuous in-service training, a lecture to pharmacy staff, and provision of supportive educational material greatly improved the overall medicine administration process in patients with swallowing problems and feeding tubes.

Drug diversion of Oxycontin in chronic pain syndrome.

Abstrsct A case is described in which a man with chronic pain syndrome (CPS) presented to a city General hospital in suicidal crisis after referral from a provincial psychiatric unit, having taken an overdose of a variety of medications, precipitated by the absence of his opioid (Oxycontin) analgesia which he had been abusing intra-nasally. This is to our knowledge the first reported case in Europe of drug diversion from oral to intranasal use of Oxycontin, a controlled-release preparation of the synthetic opiate, oxycodone hydrochloride. There is also a dearth of reference to the abuse potential of this agent in the European literature. As sufferers from chronic pain syndrome increase in number, and opiate prescription rates worldwide are maintained, this case highlights the potential of opiate abuse or dependence and drug diversion emerging as a significant medical problem in CPS patients in Europe.

Understanding intestinal cysteamine bitartrate absorption

To test the hypothesis that a controlled-release preparation of cysteamine, with fewer daily administrations, would improve the quality of life for patients with cystinosis. A specifically designed nasoenteric tube was used to administer cysteamine directly into the stomach, small intestine (SI) and colon and serial plasma cysteamine, serum gastrin and leukocyte cystine levels were measured. Eight control subjects (mean age 23.2 years) and 6 subjects with cystinosis (mean age 15.2 years) were studied. Cysteamine absorption (maximum concentration and area under the curve of the concentration-time gradient) was greater from the SI than stomach or cecum (P < .01). Leukocyte cystine depletion was greater after delivery of cysteamine into the SI than stomach or cecum; this effect was associated with the plasma cysteamine maximum concentration and area under the curve (P < .001 and < .02, respectively). Gastrin levels were not affected by site of drug delivery and were elevated only in patients with cystinosis with gastrointestinal symptoms. The absorption of cysteamine and the effect of this agent on leukocyte cystine depletion are more profound after SI administration. Enteric-coated cysteamine, targeted for SI release, may require fewer daily dosages. Not all patients with cystinosis require acid-suppression therapy.

The use of an in vitro dissolution and absorption system to evaluate oral absorption of two weak bases in pH-independent controlled-release formulations

The aim of this study was to compare the oral absorption of two weak bases including their pH-independent controlled-release preparations using an in vitro evaluation system. This system is able to simulate dissolution of drugs, pH change and permeation of drugs through the epithelial cell membrane in the gastrointestinal tract. Albendazole-polymers solid dispersion and pH-independent sustained-release granules of dipyridamole were prepared by using a solvent method. Elution profiles and predicted absorption of these preparations in gastric pH conditions similar to those in healthy subjects and patients with achlorhydria were compared with those of a physical mixture and commercial tablets. When a physical mixture or commercial tablets were used, the elution profile and predicted absorption of both albendazole and dipyridamole were extremely pH-dependent. On the other hand, when a solid dispersion and granules were used, elution and predicted absorption were not affected by changes in pH of the flowing solution in a drug-dissolving vessel. These results are in agreement with the results of our previous in vivo study using gastric acidity-controlled rabbits. Our results suggest that this in vitro system is useful for the evaluation of oral absorption of pH-independent controlled-release preparations.

Bibliography of Monographic Works on Drug Delivery Systems and Controlled-Release Preparations

A bibliography of English language books, conference proceedings, and journal special issues, published between 1980 and 2004, covering drug delivery systems and controlled release preparations for therapeutic and prophylactic agents was compiled as an aid for students and researchers. This work may also serve those who wish to track the history of this field of study and aid in the development of related library collections.

Formulation and in vitro evaluation of ethyl cellulose microspheres containing zidovudine

The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of zidovudine using ethyl cellulose as the retardant material with high entrapment efficiency and extended release. Microspheres were prepared by water-in-oil-in-oil (w/o/o) double emulsion solvent diffusion method. A mixed solvent system (MSS) consisting of acetonitrile and dichloromethane in a 1:1 ratio and light liquid paraffin were chosen as primary and secondary oil phases, respectively. Span 80 was used as the surfactant for stabilizing the secondary oil phase. The prepared microspheres were white, free flowing and spherical in shape and characterized by drug loading, infrared spectroscopy (IR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release studies were performed using PH 7.4 phosphate buffer. The drug loaded microspheres showed 41–55% of entrapment and release was extended up to 18–20 h. The infrared spectra and DSC and DTA thermograms showed stable character of zidovudine in the drug loaded microspheres and revealed the absence of drug-polymer interactions. SEM studies showed that the microspheres are spherical and porous in nature. Data obtained from in vitro release were fitted to various kinetic models and high correlation was obtained in the Higuchi model. The drug release was found to be diffusion controlled.

A clinical evaluation of controlled-release dinoprostone for cervical ripening – a review of current evidence in hospital and outpatient settings

Labor induction is used in approximately 20% of pregnancies in Europe and North America. Prostaglandins and prostaglandin analogs are favored when women undergoing labor induction have an unripe cervix. Controlled-release dinoprostone, delivered over 24 h from a vaginal insert, results in cervical ripening within 12 h in most women. It is marginally more effective than immediate release formulations and has similar efficacy to misoprostol, a prostaglandin E1 analog used off-label for this indication. The controlled-release preparation offers many advantages compared with an immediate-release formulation: a single application is sufficient; it is less invasive; it is easily administered and removed, allowing greater dose control. The most significant adverse effect, uterine hyperstimulation, with and without an effect on fetal heart rate, occurs in 5-15% of patients, which is comparable with other formulations or misoprostol. The insert can be removed easily on the first sign of uterine hyperstimulation, or as soon as labor starts. The efficacy and safety of controlled-release dinoprostone are comparable whether it is used in the outpatient or the inpatient setting. For low-risk women, outpatient use may be a highly attractive option, potentially reducing hospital costs, and improving patient convenience. The ease of use of controlled-release dinoprostone and women's satisfaction emphasize its benefits over many other agents used to ripen the cervix.

Pain in Parkinson's Disease.

Pain is reported by nearly 50% of patients with Parkinson's disease. In some patients, it can be more debilitating than the motor deficits. In order to identify the appropriate treatment strategy for each patient, it is useful to categorize pain syndromes as follows: 1) low DOPA (end of dose wearing off, diphasic, or early morning) painful states are associated with inadequate levels of dopamine receptor stimulation; 2) high DOPA (peak dose) painful states occur at times of maximum levodopa efficacy; and 3) many patients report pain that has no obvious relation to dopaminergic medications or may even be caused by other conditions. Low DOPA painful states are best treated by trying to provide more continuous dopaminergic stimulation and thereby reduce or prevent the number and duration of "off" periods. Adding or increasing the dose of direct-acting dopamine receptor agonists or of catechol-o-methyl transferase inhibitors is the best first-line strategy. Other approaches include increasing the frequency of immediate-release levodopa preparations or using controlled-release preparations. More invasive approaches should be considered only when simpler methods fail. These include deep brain stimulation to the pallidum or the subthalamic nucleus, or direct duodenal continuous infusion of levodopa in patients who are unable to undergo surgery. Pain associated with excessive dopaminergic stimulation usually is a result of dystonia or severe chorea. Reduction of levodopa is the first step in attempting to diminish high DOPA states, followed by reduction or cessation of other dopaminergic agents such as selegiline, catechol-o-methyl transferase inhibitors, or direct-acting dopamine receptor agonists. Adding amantadine can reduce chorea significantly and it should be tried if the potential and actual side effects are tolerable to the patient. Deep brain stimulation is a good final option if medication adjustments are ineffective. Nonspecific pains of Parkinson's disease can be difficult to treat. The effective use of central pain suppressant or analgesics is anecdotal and difficult to verify. In untreated early disease, generalized pain or pain related to joint or muscle immobility may be reduced by effective treatment of the underlying Parkinson's disease.

Single‐point plasma or urine dextromethorphan method for determining CYP3A activity

Dextromethorphan is used widely in vivo to phenotype the polymorphically expressed cytochrome P450 (CYP) 2D6. Also dextromethorphan is N-demethylated in vivo to 3-methoxymorphinan by human CYP3A4/5. The metabolic ratio (MR) of dextromethorphan/3-methoxymorphinan in plasma, saliva and urinary were examined as a possible in vivo probe of CYP3A activity. In limited previous studies, 4 h urinary samples were collected for determining the MR. To evaluate the repeatability and validity of previously reported and other potential phenotyping methods, the MR from urine samples (at various intervals), from plasma and from saliva (at varying time points) were determined after repetitive single doses of immediate-release or repetitive multiple doses of controlled-release dextromethorphan preparations. For the single-dose study, each of 12 subjects received 15 mg of immediate-release dextromethorphan in periods II and I, respectively, with a 1 week washout period. For the multiple dose study, each of 16 subjects received 60 mg controlled release dextromethorphan twice daily for 5 days in periods I and II, respectively, with a 2 week washout period. Dextromethorphan and 3-methoxymorphinan are assayed by high-performance liquid chromatography. In the single-dose study, all of the urine MR revealed good repeatabilities for the periods (paired t-test). The urine MR at any time interval of 0-6 h, 0-8 h and 0-12 h correlated significantly with the MR from 0-24 h urine (r>0.8, p<0.05). In the multiple-dose study, all MR revealed good repeatabilities for the two periods (paired t-test). The plasma MR at any time between 0.5 h and 12 h, the saliva MR at 12 h and the urine MR at any interval between 0-2 h, 0-4 h, 0-6 h, 0-8 h, 0-12 h and 0-24 h could predict the MR from AUCtau(ss). In conclusion, the urine sample as 0-6 h, 0-8 h or 0-12 h in the single immediate-release dose (15 mg) or in the multiple controlled-release dose (60 mg) procedure, the saliva sample at 12 h, the urine sample at 0-2 h, 0-4 h, 0-6 h, 0-8 h, 0-12 h, 0-24 h or all plasma-sampling points 0.5-12 h could be used as the dextromethorphan MR for determining the CYP3A activity.

Development of a new dissolution test method for an oral controlled release preparation, the PVA swelling controlled release system (SCRS)

In vitro dissolution tests of novel controlled release tablets, the poly(vinyl alcohol) (PVA) swelling controlled release system (SCRS), were performed by various methods under different conditions in the sinking state in water. The in vitro release profiles of various tests were almost the same and faster than the in vivo absorption profiles calculated from the plasma drug concentrations of humans. A novel dissolution test method was developed considering the gastrointestinal tract (GI) conditions. PVA particles were used as the filler in a flow-through cell. PVA particles swelled with water were put in the flow-through cell and the tablet was buried in PVA. The test medium was dropped from the top of the cell, and the dissolution medium that dripped from the bottom of the cell was collected and assayed. The in vitro dissolution profile determined by this method was similar to the in vivo absorption profile against other in vitro methods in the sinking state in water. Furthermore, a good correlation between in vitro and in vivo for the two different release rate preparations was obtained using a flow pattern imitating the GI transition.

Drug treatment of epilepsy in elderly people: focus on valproic Acid.

Despite old age being the commonest time of life to develop epilepsy, relatively little is known about the condition in later years. Antiepileptic drugs (AEDs) are the mainstay of treatment and valproic acid (VPA) has been prescribed for older patients with seizures for over 35 years. VPA is available in a variety of formulations. The drug is generally rapidly absorbed, although there are no data on the extent of oral absorption in the elderly. The volume of distribution (Vd) and elimination half-life have been compared in older and younger patients. One study reported no change in either parameter between elderly and younger patients (Vd: 0.16 vs 0.14 L/kg; elimination half-life: 15.3 vs 13.0h), the other found an increase in both for older patients (Vd: 0.19 vs 0.13 L/kg; elimination half-life 14.9 vs 7.2h). Total VPA clearance is similar in young and elderly subjects. The drug does not induce the metabolism of hepatic enzymes, but can act as a metabolic inhibitor, raising plasma concentrations of lamotrigine, phenobarbital (phenobarbitone), carbamazepine-10-11-epoxide, lorazepam, nimodipine and zidovudine. Concomitant use of VPA may also lead to an elevation in phenytoin, diazepam, warfarin, amitriptyline and chlorpromazine concentrations. A number of enzyme-inducing AEDs such as phenytoin, phenobarbital, primidone and carbamazepine can increase the clearance of VPA. Plasma concentrations of VPA may also rise when the drug is administered with felbamate, stiripentol, aspirin (acetylsalicylic acid), naproxen, phenylbutazone, isoniazid, fluoxetine and chlorpromazine. The majority of elderly patients present with partial and/or secondary generalised seizures, although a few have long-standing primary generalised seizures. Results from meta-analyses and randomised studies of patients comparing VPA with other AED monotherapies suggest that the drug is as effective as carbamazepine, phenytoin and phenobarbital in treating these seizure types. Although some of these studies recruited older patients, there have been no randomised double-blind trials examining the efficacy of VPA with other AEDs in an exclusively elderly cohort. There is no direct correlation between efficacy and plasma VPA concentrations. The majority of older patients require lower doses of AEDs than younger adults. Higher VPA doses may be needed in patients taking drugs which induce hepatic microsomal enzymes. Once-daily dosing of the controlled-release preparation can help to improve compliance and may render some frail elderly people seizure free. There is a perception that the elderly are generally more susceptible to the adverse effects of AEDs than younger adults, although there are few data to validate this claim. Dose-dependent and idiosyncratic reactions may be more frequent. Common adverse effects of VPA include gastrointestinal symptoms and tremor. Slow-dose escalation and controlled-release preparations may minimise these. In summary, VPA is a long established AED. Its broad spectrum of action and dosing schedule are favourable properties for its use in older people. To accurately establish the place of this and other AEDs in treating elderly patients with epilepsy, well designed clinical trials are urgently required in this vulnerable population.

Modern Technologies for the Creation of Controlled Release Preparations of Isosorbide Dinitrate and Acylated Phenothiazine Derivatives for Peroral Administration (A Review)

Modern Technologies for the Creation of Controlled Release Preparations of Isosorbide Dinitrate and Acylated Phenothiazine Derivatives for Peroral Administration (A Review)

Safety and efficacy of controlled-release oxycodone: a systematic literature review.

Prescriptions for controlled-release oxycodone, a narcotic analgesic, recently contributed to a dramatic increase in pharmacy costs for a large private insurance company. To determine whether this agent offered clinical benefits over other available drugs that would justify its significantly greater cost, a systematic review of 16 clinical trials was undertaken. The review suggested that immediate-release and controlled-release preparations of oxycodone have similar efficacy and comparable side effect profiles. Controlled-release oxycodone has the advantage of less frequent dosing than immediate-release oxycodone; however, other agents may be dosed infrequently at much lower costs. For patients requiring a controlled-release opioid treatment, controlled-release morphine and methadone should be considered because they appear to be as effective as oxycodone and cost considerably less. Controlled-release oxycodone may be appropriate for some patients, particularly if they cannot tolerate other controlled-release or long-acting opioid analgesics.

Oral controlled release formulation of diclofenac sodium by microencapsulation with ethyl cellulose

The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of diclofenac sodium (DFS) using different proportions of ethyl cellulose (EC) as the retardant material to extend the release. The formulated microcapsules were then compressed into tablets to obtain controlled release oral formulations. Phase separation-coacervation technique was employed to prepare microcapsules of DFS using different proportions of EC in cyclohexane. Physical characteristics of microcapsules and their tablets, in vitro release pattern of the designed microcapsules and their tablets prepared from them were studied using USP dissolution apparatus (USP 2000) type 2 (paddle method) in triple distilled water. The prepared microcapsules were white, free flowing and spherical in shape, with the particle size varying from 49.94-52.72 #119 m. The duration of DFS release from microcapsules was found to be directly proportional to the proportion of EC and, thus, coat thickness. All tablets were of good quality with respect to appearance, drug content uniformity, hardness, weight variation, friability and thickness uniformity. In vitro release study of the tabletted microcapsules in triple distilled water showed a zero order release kinetics and extended release beyond 24 h. A good correlation was obtained between drug release (t 60) and proportion of EC in the microcapsules. In the case of tabletted microcapsules, very good correlation could be established between t 60, proportion of EC, weight of the tablets and between release rate constant (K) and proportion of EC. All the formulations were highly stable and possessed reproducible release kinetics across the batches.

Parkinson's Disease: Initial Treatment with Levodopa or Dopamine Agonists.

The question of whether to use levodopa (LD) or dopamine agonists as initial therapy in Parkinson's disease has been a controversy for nearly 20 years. There are several issues relating to this treatment regimen that may effect ones decision. Review of them results in the following conclusions: LD does not cause the onset of motor fluctuations and dyskinesia; it probably relates to disease progression. Tolerance does not develop with long-term LD therapy. LD is not toxic. LD decreases mortality in Parkinson's disease. Motor fluctuations can occur with dopamine-agonist monotherapy, but the actual frequency is as yet unknown. Dopamine agonists are not neuroprotective. Clinical trials have indicated that LD remains the most potent symptomatic therapeutic agent available. Dopamine agonists do provide some symptomatic relief when used alone in early Parkinson's disease. Standard preparations of LD have the same effect on early disease as controlled release preparations. Dopamine agonists cause less dyskinesia and fluctuations. These conclusions indicate that both drugs are effective symptomatic agents with their own positive and negative aspects. There is no incorrect choice. It is reasonable to start young onset patients (younger than 50 years of age) with an agonist, because they seem to be more prone to develop motor fluctuations and dyskinesia. However, if employment is in jeopardy then LD may be needed. Because agonists cause more hallucinations, freezing, and somnolence, problems of particular relevance to the elderly (older than 70 years), then LD would be the best agent for older onset patients. In general, but particularly for those falling in between these age groups, treatment should be individualized. In this time of cost effectiveness, LD remains the least expensive of these agents.

Oxybutynin and the overactive bladder.

Oxybutynin is a tertiary amine, which undergoes an extensive first-pass metabolism. It has an active metabolite, N-desethyl oxybutynin, and the effect of oral oxybutynin is to a large extent exerted by this metabolite. Oxybutynin has both an antimuscarinic and a direct muscle relaxant effect, and, in addition, local anesthetic actions. Most probably, oral oxybutynin exerts its effects on the overactive bladder (OAB) by an antimuscarinic action. Several studies have shown that oral oxybutynin is effective in controlling OAB. Admininistred intravesically, it can increase bladder capacity and produce clinical improvement both in patients with hypereflexia and in other types of OAB with few side effects. Adverse effects related to the antimuscarinic activity occur frequently and can necessitate treatment discontinuation in up to 25% of patients, depending on the dosage. A controlled-release preparation has recently been introduced. Oxybutynin has a well-documented efficacy in the treatment of detrusor overactivity, and is a drug of first choice in patients with this disorder.