Timed-release preparation

Phentermine is available as an immediate-release and a sustained-release product. In conjunction with a healthy lifestyle, 30 to 37.5 mg of phentermine is administered once daily, typically before breakfast or 1 to 2 hours following the morning meal. The dosage should be individualized some patients maybe managed adequately at 15 to 18.75 mg daily, whereas a dose of 18.75 mg twice daily may be used to minimize side effects, excluding insomnia. To lessen the risk of insomnia, dosing phentermine in the evening should be avoided. Timed-release preparations of phentermine are not recommended because phentermine s half-life is approximately 20 hours.39... 

Figure 4 (a) Assembly for testing timed-release preparations. Redrawn from a letter typewritten on USP paper in 1957. Source From Ref. 23. (b) Continuous flow dissolution apparatus. Source From a 1968 publication by Pemarowski. 

Depending on the country where the drug is manufactured, a number of different time-release preparations are available. Palladone , a controlled-release preparation consisting of hydromorphone HC1 pellets, was withdrawn from the U.S. market in 2005. When taken with alcohol the pellets rapidly released their contents leading to dangerously elevated peak plasma concentrations.60 Interaction with ethanol and dose dumping is not the only concern. Any CNS depressant may enhance the depressant effects of hydromorphone. 

The degree of ionization under physiologic conditions Product formulation characteristics Disintegration and dissolution rates for solid dosages Drug release characteristics for timed-release preparations Patient factors... 

Fukui, E., Uemura, K., and Kobayashi, M. (2000), Studies on applicability of press-coated tablets using hydroxypropylcellulose (HPC) in the outer shell for timed-release preparations, I. Controlled Release, 68, 215-223. 

Most drugs are absorbed across the GI tract by passive diffusion, but a variety of drug physicochemical factors influence fhe exfenf of absorption. These factors include molecular weight, lipid solubility, ionization as well as disintegration and dissolution rates. In addition, drug absorption may be dependent on the dosage form selected (e.g., a liquid, a tablet that may need to be crushed, or a sustained-release product), and the particular brand selected. For timed-release preparations, the release characteristics must also be taken into consideration. 

Rader Jl, Calvert RJ, Hathcock JN. Hepatic toxicity of unmodified and time-release preparations of niacin. Am J Med 1992 92 77-81. 

Drug release characteristics for timed-release preparations... 

Hydrogels are used in pharmaceutical preparations (2) as solubility enhancers or as time-release preparations. The hydro-... 

The nomenclature for nicotinic acid formulations can be confusing. Nicotinic acid is available over the counter in an immediate-release (crystalline), and slow-release or timed-release form. A shorter acting, timed-release preparation referred to as intermediate release or extended release nicotinic acid is available by prescription. Due to the potential for side effects, medical supervision is recommended for the use of nicotinic acid as a cholesterol-lowering agent. 

Fnkni E, Uemura K and Kobayashi M (2000), Stndies on applicability of press-coated tablets nsing hydroxypropylceUnose in the onter shell for timed-release preparation J Control Release, 68(2), 215-223. DOI 10.1016/80168-3659(00) 00261-3. 

Because of die risk of tolerance to oral nitrates developing, die primary care provider may prescribe die short-acting preparations 2 to 3 times daily, witii die last dose no later than 7 pm and die sustained release preparations once daily or twice daily at 8 AM and 2 PM. 

Any extended release preparation ° CR—controlled-release ° EC—enteric coated ° LA—long-acting ° SR—sustained release 0 TR—time release ° SA—sustained action ° SL—sublingual ° XL—extended length ° XR—extended release... 

Fig. 8 Comparison of time-release profiles from three different preparations of betaxolol (—) drug solution representing marketed product (--------) supension formulation (-----------) gel formulation.

Lithium is usually initiated with low to moderate doses (600 mg/day divided into two to three doses) for prophylaxis, and higher doses (900 to 1,200 mg/day, divided into two to three doses) for acute mania. Immediate-release preparations should be given two to three times daily, whereas extended-release products can be given once or twice daily. After patients are stabilized, many patients can be switched to once-daily dosing. 

In this study, we demonstrate new pH/temperature-sensitive polymers with transitions resulting from both polymer-polymer and polymer-water interactions and their applications as stimuli-responsive drug carriers [22-23], For this purpose, copolymers of (Ai,Ai-dimethylamino)ethyl methacrylate (DMAEMA) and ethylacrylamide (EAAm) [or acrylamide (AAm)] were prepared and characterized as polymeric drug delivery systems modulated for pulsatile and time release. 

Sustained-release Do not substitute sustained-release (modified-release, timed-release) nicotinic acid preparations for equivalent doses of immediate-release (crystalline) nicotinic acid. 

To avoid the side effects of sulfapyridine, various preparations to target 5-ASA directly to sites of disease have been formulated. Also known as mesalamine, 5-ASA has been formulated in oral forms (Pentasa, Asacoi). Pentasa is a time-release capsule that releases the drug throughout the GI tract. Asacoi is a pH-dependent-release preparation that delivers drug to the distal small bowel and colon. The response of ulcerative colitis to this formulation appears to be identical to that seen with sulfasalazine. Mesalamine can also be administered as a suppository (Canasa) or enema (Rowasa) for distal colonic disease. 

At one time, sustained-release preparations were thought to reduce renal toxicity, but more recent evidence has cast doubt on this assumption ( 313). A patient on long-term maintenance lithium should have renal function monitored periodically (i.e., every 12 months) with a urinalysis, BUN, and creatinine. If abnormal, a more intensive evaluation should include 24-hour urine osmolality and creatinine clearance. It is advisable to reduce maintenance lithium to optimal minimal dose-blood levels and, if possible, to avoid concomitant antipsychotics, which may enhance toxicity. Some data support the use of a once-a-day dose schedule to minimize peak lithium concentrations over a 24-hour period (314). 

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