Hydrocodone formulations

Fatmi, A.A. Williams, G.V. Simultaneous determination of acetaminophen and hydrocodone bitiu rate in solid dosage forms by HPLC. J.Liq.Chromatogr., 1987,10,2461-2472 [simultaneous hydrocodone formulations]... 

Drug Formulations On September 10, 2013, the Food and Drug Agency (FDA) approved a novel oral extended release hydrocodone formulation, hydrocodone bitartrate (Zohydro ER) [39 ]. Interestingly, the FDA advisory panel earlier in 2013 had voted 11-2 against approval of Zohydro, but despite this recommendation, Zohydro was approved and is available in the United States. Zohydro is an oral capsule available in 10,15,20,30,40 and 50-mg... 

Codeine (Figure 31-1), oxycodone, dihydrocodeine, and hydrocodone are all somewhat less efficacious than morphine (they are partial agonists) or have adverse effects that limit the maximum tolerated dose when one attempts to achieve analgesia comparable to that of morphine. These compounds are rarely used alone but are combined in formulations containing aspirin or acetaminophen and other drugs. 

SCHEDULE II Certain barbiturates, cocaine, codeine, codeine + acetaminophen (depends on dose and formulation), fentanyl (depends on dose), hydrocodone, hydromorphone, meperidine, methadone, morphine (depends on combination with other pain relievers), oxycodone, propoxyphene... 

This type of CrDDS is exemplified by the development of Pennkinetic system (by Pennwalt Pharmaceuticals), which permits the formulation of oral liquid-type dosage forms with sustained release of a combination of hydrocodone and chlorpheniramine (Tussionex ). - ]... 

Absorption Oral broavailability is variable depending On drug and formulation (morphine < hydrocodone and oxycodone < methadone). The exception is fentanyl, which is very poorly... 

Many analgesic effectiveness studies involving combination drug formulations (an opioid combined with a nonopioid) have been reported. For example, in the treatment of moderate to severe postoperative obstetric or gynecologic pain, 2-tablet dose of hydrocodone 7.5 mg with ibuprofen 200 mg was comparable in efficacy to the 2-tablet dose of oxycodone 5 mg and acetaminophen 325 mg. Obviously both of these treatments were superior to the placebo [23]. In contrast, for treatment of chronic pain, the 2-tablet dose of hydrocodone 7.5 mg and ibuprofen 200 mg was more effective than either the 1 -tablet dose of this combination or the 2-tablet dose of codeine 30 mg and acetaminophen 300 mg combination [24]. In a double-blind, randomized controlled trial involving 118 patients with chronic cancer pain, the combination formulation of hydrocodone (25 mg/d) and acetaminophen (2500 mg/d) was effective in relieving pain in 56.5% of the patients [25]. 

Opioids 2-3 days typically Up to 6 days with sustained-release formulations Up to 1 week with prolonged or heavy use Since the assay was made to detect morphine, detection of other opioids, such as codeine, oxycodone, hydrocodone, and other semisynthetic opioids, may be limited. Some synthetic opioids, e.g., fentanyl and meperidine, may not be detected. Drugs such as rifampin and some fluoroquinolones may cause false-positive results depending on the assay. 

Wallo, W.E. D Adamo, A. Simultaneous assay of hydrocodone bitartrate and acetaminophen in a tablet formulation. J.Pharm.Sci., 1982, 71, 1115-1118... 

Alvi, S.U. Castro, F. A stability-indicating simultaneous analysis of acetaminophen and hydrocodone bitartrate in tablets formulation by HPLC. J.Liq.Chromatogr., 1987, 10, 3413-3426 [stability-indicating simultaneous acetaminophen, hydrocodone, hydromorphone tablets column temp 30] Gibson, M. Jefferies, T.M. Soper, C.J. Isolation of codeine and norcodeine from microbial tremsformation liquors by preparative high-performance liquid chromatography. Analyst, 1987,112, 1667-1670... 

Hydrocodone bitartrate is approximately threefold more effective on a weight basis as an oral antitussive medication compared to codeine. Hydrocodone also has greater analgesic activity and abuse potential than codeine. Hydrocodone is only available as a Schedule III prescription agent in combination formulations for cough suppression. 

While primarily employed as an analgesic, hydromor-phone is an excellent cough suppressant and is associated with less histamine release and pruritus than codeine. Hydrocodone is only available for oral administration, as either a tablet, capsule, or syrup formulation, and is usually combined with acetaminophen or ibuprofen. Standard immediate-release tablets provide 4-6 h of analgesia for patients with... 

Hydrocodone has a half-life of 3.8 boms, peak effect at 1.3 hours, and a duration of 4.6 hours. It is metabolized by the liver and excreted primarily in urine. Hydrocodone is oxidized to hydromorphone by cytochrome P450 2D6. The extended-release formulation has measurably different pharmacokinetics following a single dose of 1,2 or 3 HC/ APAP CR tablet(s), the mean maximum plasma concentration (C ) ranged from 13.3 to 36.8 ng/mL for HC and 2.01 to 6.68 ng/mL for APAP. The mean time to reach (T ) was 6.0-6.7 hours for HC and 1.1-1.3 hours for APAP. Following twice-daily dosing of 2 HC/APAP CR tablets for 3 days, steady-state HC/APAP concentrations were attained by 24 hours [3,4]. The mean on day 3 was 37.0 ng/mL for HC and 4.96 ng/mL for APAP. Systemic exposures of HC and APAP demonstrated a dose-proportional increase from one to three tablets. Steady-state concentrations were reached by 24 hours with minimal accumulation following twice-daily administration. Thus, it can be taken every 12 hours [4]. 

Controlled-release HC/APAP is only formulated as an oral preparation containing a standard dose of hydro-morphone 15 mg and acetaminophen 500 mg, to be administered every 12 hours. Phase 3 study data indicate that 12-hour dosing provided effective pain relief for patients with moderate to severe acute and chronic pain. The drug should not be crushed or tampered with as that will change the pharmacokinetics of the extended-release hydrocodone. At this time, the manufacturer has not disclosed whether HC/APAP CR will be manufactured in a tamper-resistant formulation. 

Ease of use, tolerability, and efficacy this new controlled-release formulation of hydrocodone offers the... 

---