FIELD OF THE INVENTION:
The invention relates .to oral pharmaceutical dosage forms and the use thereof. More
specifically, this invention relates to controlled release oral" pharmaceutical dosage forms and
their use to deliver actives.
BACKGROUND OF THE INVENTION:
Developing drugs for oral delivery is challenging due to several factors, including the need
for sustained release over the duration of time the drug is in the gastrointestinal tract.
Achieving sustained release can be accomplished through methods such as delayed-release
coatings or slow disintegration of the tablet. However, once ingested, tablets are subjected to
mechanical and chemical stresses that can compromise controlled release. The risk of drug
·abuse is another challenge in developing oral dosage forms,. particularly for opioids, eNSdepressants,
and stimulants, which are commonly abused. Stimulants, such as
dextroamphetamine and methylphenidate, increase brain activity, leading to an increase in
alertness, attention, and energy, along with increases in blood pressure, heart rate, and
respiration. The abuse of stimulants has been a growing. problem, with over 1.4 million
people over the age of 12 reporting abuse. Short-acting immediate-release formulations are
the most commonly abused, with the drug often extracted and inhaled or injected. Solid
dosage forms, like tablets, are particularly ·susceptible to abuse, as they can be ground down
into a powder for nasally inhaling or dissolved in alcohol or water to make an injectable
solution.
Drug delivery of pharmaceuticals, particularly for oral administration, is a widely studied
field. Many drugs, such as antihistamines, decongestants, and analgesics, are delivered in the
form of solid tablets. Controlled and sustained release formulations have also been available
for many years, offering advantages such as extended release times and improved patient ·
compliance. However, creating oral controlled release formulations that can withstand the
mechanical and chemical stresses of passing through the gastrointestinal tract remains a
challenge. Acidic environments, digestive enzymes, and peristalsis can all interfere with the
controlled release of the drug. Additionally, the potential for substance abuse is a major
concern with certain drugs, particularly opioids, CNS depressants, and stimulants. Addressing
these challenges is essential for developing effective and safe drug delivery systems.
According to.a 1999 survey by the National Institute on Drug Abuse (NIDA), prescription
2
drug abuse was prevalent in approximately 2% of the population over the age of 12, with
opioids, CNS depressants, and stimulants being the most commonly abused drug classes.
'
Developing a controlled-release oral dosage form that reduces the potential for drug abuse,
particularly for stimulants, is a pressing need.
Summary of the invention:
The present invention· provides an oral oral pharmaceutical preparation comprising a
pharmacologically active agent and a controlled release carrier system, wherein the controlled
release carrier system comprises a high viscosity liquid carrier material ("HVLCM"), a
network structure forming agent, a rheology regulator, a hydrophilic agent, and a solvent, and
imparts abuse resistance to the formulation, wherein the in vivo absorption of the active agent
from the formulation is .enhanced when the formulation is administered with food and the in
vivo release of the active agent from the controlled release carrier system is substantially free
from food effects.
In another. embodiment, the controlled release carrier system further comprises at least one
viscosity enhancer and a stabilizer.
In another embodiment, the HVLCM comprises sucrose acetate isobutyrate ("SAIB") and the
network structure forming agent comprises cellulose acetate butyrate ("CAB"), cellulose
acetate phthalate, ethyl cellulose, hydroxypropyl methyl cellulose, or cellulose triacetate and
the rheology regulator comprises isopropyl myristate ("IPM"), capricyl/capric acid
triglyceride, ethyl oleate, triethyl citrate, dimethyl phthalate, or benzyl benzoate.
In another embodiment of the present invention the hydrophilic agent comprises
hydroxyethyl cellulose ("HEC"), hydroxypropyl cellulose, carboxymethyl cellulose,
polyethylene glycol, or polyvinylpyrrolidone, and the solvent comprises triacetin, N-methyl-
2-pyrrolidone, 2-pyrrolidone, dimethyl sulfoxide, ethyl lactate, propylene carbonate, or
glycoflor.
In yet another embodiment of the present invention, the viscosity enhancer comprises silicon
dioxide and the stabilizer comprises butylhydroxytoluene ("BHT"); and the
pharmacologically active agent comprises an opioid, CNS inhibitor, or CNS stimulant, which
is particularly likely to be abused, diverted, or otherwise misused, and preferably comprises
opioids, amphetamines, or methylphenidate as either salts or free bases in either case.
3
In another embodiment, the present invention provides a process for preparmg an oral
pharmaceutical preparation comprising a pharmacologically active agent and a controlled
release carrier system, comprising mixing the pharmacologically active agent with a high
viscosity liquid carrier material, a network structure forming agent, a rheology regulator, a
hydrophilic agent, and a solvent to form the controlled release carrier system, and
incorporating the controlled release carrier system into a· suitable dosage form, wherein the
controlled release carrier system imparts abuse resistance to the forrimlation, and in vivo
absorption of the active agent from the formulation is enhanced when the formulation is
administered with food and in vivo release of the active agent from the controlled release
carrier system is substantially free from food effects.
In another embodiment, the present invention further provides a abuse-resistant oral
pharmaceutical preparation comprising a pharmacologically active agent and a controlled
release carrier system, wherein the controlled release carrier system is in a steady state C min
within each dosing interval and C max fluctuation is less than or equal to the therapeutic
index of the aCtive agent. The active agent's absorption is enhanced when the preparation is
administered with food, and the formulation is still safe even when ingested without food,
providing in vivo release. The controlled release carrier system further provides a reduced
risk of misuse or abuse, characterized by having a low in vitro solvent-extraction rate of the
active agent from the formulation and/or not
Objectives of the present invention:
It is a pnmary objective is to provide an oral pharmaceutical preparation containing a
pharmacologically active agent and a controlled release carrier system.
It is further objective of the present invention is to provide that in vivo absorption of the
active agent from the formulation is enhanced ·when the formulation is administered with
food, or conversely, in· vivo relea.se of the active agent .from a controlled release carrier
system.
It is further objective of ·the present invention to provide an oral pharmaceutical preparation
containing a pharmacologically active agent and a controlled release carrier system.
It is further objective of the present invention to provide the formulations to reduced risk of
misuse or abuse, eg, reduction of such misuse or abuse.
4
Description of the invention:
Those skilled in the art will be aware that the present disclosure is subject to variations and
modifications other than those specifically described. It is to be understood that the present
disclosure includes all such variations and modifications. The disclosure also includes all
such steps of the process, features of the product, referred to or indicated in this specification,
individually or collectively, and any and all combinations of any or more of such steps or
features.
The present disclosu.re is not to be limited in scope by the specific embodiments described
herein, which are intended for the purposes of exemplification only.
The present invention involves a method and a system for preventing the abuse of drugs with
high potential for addiction, such as opioids, CNS inhibitors, and stimulants. Opioids are
potent anesthetics used to relieve pain, including morphine, codeine, oxycodone, and
fentanyl. CNS inhibitors reduce brain activity and cause sedative effects, and they include
barbitalates and benzodiazepines. Stimulants increase brain activity and are prescribed to
treat narcolepsy, ADHD, and depression, such as dextroamphetamine and methylphenidate ..
These drugs are often abused by grinding them into powder or dissolving them in alcohol or
water for injection. Ingesting high doses of these drugs can lead to severe health problems
and death. Solid formulations are particularly vulnerable to abuse, and highly addictive drugs
like oxycodone are frequently abused by crushing or grinding the. tablets. The present
invention aims to prevent drug abuse by incorporating physical and chemical barriers into the
drug formulations, such as tamper-evident packaging, controlled release mechanisms, and
chemical deterrents. These barriers can discourage drug abusers from tampering with the
drugs and reduce the risk of drug abuse.
The present invention provides an abuse-resistant oral pharmaceutical preparation comprising
a pharmacologically active agent and a controlled release carrier system. The aim of the
invention is to enhance in vivo absorption of the active agent from the formulation when
administered with food, or conversely, in vivo release of the active agent from the controlled
release carrier system, while minimizing food effects. Additionally, the invention aims to
reduce the risk of misuse or abuse of the preparation. The controlled release carrier system
comprises a high viscosity liquid carrier material ("HVLCM"), a network structure forming
5
agent, a rheology regulator, a hydrophilic agent, and a solvent. Each object of the invention
can be further .characterized by a unique .combination of pharmaceutical excipients in the
controlled release carrier system. The formulation can contain additional components such as
a viscosity enhancer and a stabilizer for added abuse resistance. The low in vitro solvent
extraction rate of the active agent and the ;~bsorption of the active agent from the formulation
when co-ingested with alcohol are not significantly affected.
The present invention pertains to an abuse-resistant oral pharmaceutical preparation that
contains a pharmacologically active agent and a controlled release carrier system. The carrier
system comprises a HVLCM, a network structure forming agent (such as CAB, cellulose
acetate phthalate, ethyl cellulose, hydroxypropyl methyl cellulose, or cellulose triacetate}, a
rheology modifier (such as IPM,.capricyl/capric acid triglyceride, ethyl oleate, triethyl citrate,
dimethyl phthalate, or benzyl benzoate}, a hydrophilic agent (such.as HEC, hydroxypropyl
cellulose, carboxymethyl cellulose, polyethylene glycol, or polyvinylpyrrolidone), and a
solvent (such as triacetin, N-methyl-2-pyrrolidone, 2-pyrrolidone, dimethyl sulfoxide, ethyl
lactate, propylene carbonate, or glycoflor). Additionally, the carrier system may contain a
viscosity enhancer (such as silicon dioxide) and a stabilizer (such as BHT} .
.
One objective of this invention is to provide a preparation that is substantially free from food
effects and enhances in vivo absorption of the active agent when administered with food, or
in vivo release of the active agent from a controlled release carrier system. Another objective
is to reduce the risk of abuse or misuse of the preparation. The carrier system imparts abuse
I
resistance to the formulation. In certain preferred embodiments, the active agent is an opioid,
CNS inhibitor, or CNS stimulant that is particularly likely to be abused, diverted, or
otherwise misused. Preferably, the active agent can include opioids, amphetamines, or
methylphenidate as either salts or free bases in either case.
The carrier system can be further characterized by a unique set of pharmaceutical excipients
containing a particular combination of solvent, viscosity enhancer, and the like. In some
preferred embodiments, the network structure forming agent is CAB, the first viscosity
enhancer is HEC, ·hydroxypropyl cellulose, or carboxymethyl cellulose, and the hydrophilic
solvent is triacetin, N:methyl-2-pyrrolidone, 2-pyrrolidone, dimethyl sulfoxide, ethyl lactate,
propylene carbonate, or glycoflor. The hydrophobic solvent can include IPM.
6
In another embodiment, the present invention is to offer a method for producing an oral
pharmaceutical formulation containing a pharmacologically · active compound and a
controlled-release carrier system. The carrier system comprises a high-viscosity liquid carrier
material (HVLCM), a network structure-forming agent, a rheology regulator, a hydrophilic
agent, and a solvent The production process involves several steps. Firstly, the HVLCM is
preheated. Next, the solvent is mixed with the preheated HVLCM to create a uniform
·solution of the HVLCM in the solvent. The network structure-forming agent is then dispersed.
in the solution, and 5-30% of the rheology adjuster (or in some cases, the stabilizer and
rheology adjuster) is dissolved. Following this, a solution of approximately 30% rheology
adjuster is blended with the formulation, and the pharmacologically active compound is
added and mixed. The hydrophilic agent is also added and mixed, and optionally, the
viscosity enhancer· is added and mixed with the formulation obtained in the previous step.
The remainder of the cqnditioning agent is then added and mixed with the solution. Finally,
the formulation is filled into capsules, which can be packaged into single-dose blister or
multi-dose plastic bottles, as desired. Another objective of the invention is to provide an oral
pharmaceutical formulation that can be obtained using this manufacturing or compounding
process.
Another object of the present invention IS to provide a process for preparing an oral
pharmaceutical preparation containing a pharmacologically active agent and a controlled
release carrier system. However, the controlled release carrier system includes HVLCM, a
network structure forming agent, a first viscosity enhancer, a hydrophilic solvent, and a
hydrophobic .solvent. The manufacturing process or compounding process includes the
following steps, that is,' a step of preheating the HVLCM, .a step of mixing the solvent with
the preheated HVLCM to form a uniform solution of the HVLCM in the solvent, and a
network structure forming agent. A step of dispersing the network structure forming agent in
a solution and a solution of 5 to 30% of the leo logy adjuster, or optionally 5 to 30% of the
stabilizer and the rheology adjuster. A step of mixing with the formulation, a step of adding
and mixing a pharmacological activator, a step of adding and mixing a hydrophilic agent, and
optionally a step of adding and mixing a viscosity enhancer, and adding the rest of the
rheology. modifier. Includes the step of adding and adding. ln addition, the process can
include filling capsules with the formulation obtained in the process and, optionally,
packitging the filled capsules into single-dose blister or multi-dose plastic bottles.
7
Further, the present invention to provides a process for preparing an oral pharmaceutical
preparation containing a pharmacologically active agent and a controlled release carrier
system. However, the controlled release carrier system includes HVLCM, a network structure
· forming agent, a first viscosity enhancer, a hydrophilic solvent, and a hydrophobic solvent.
The manufacturing or compounding process involves the following steps, namely preheating
the HVLCM, mixing the solvent with the preheated HVLCM to form a homogeneous
solution of the HVLCM in the solvent, and optionally stabilizing. The step of mixing the
solution of the. agent with 5-30% of the rheology adjuster with the solution obtained in the
previous step and the leo logy adjuster, or if the previous step was performed, the rest of the
leo logy adjuster. A step of adding and mixing with the solution obtained in the previous step,
and in some cases, a step of adding and mixing the viscosity enhancer with the formulation
obtained in the -previous step; and adding a network structure forming agent to the solution
thus obtained. It includes a step of dissolving the network structure forming agent in a
solution by dispersing, a step of adding and mixing a pharmacological activator with the
formulation obtained in the previous step, and a step of adding and mixing a hydrophilic
agent. In addition, the process can include filling capsules with the formulation obtained in
the process and, optionally, packaging the filled capsules into single-dose blister or multidose
plastic bottles. A related object of the present invention is to provide an oral
pharmaceutical preparation that can be obtained by the above manufacturing process or
compounding process.
A further object of the present invention is to provide an abuse-resistant oral pharmaceutical
preparation containing a pharmacologically active agent and a controlled release carrier
system. The controlled release carrier system is in a steady state C min within each dosing
interval.
Control of the agent, characterized .in that'the I C max variation is less than or equal to the
therapeutic index of the active agent in vi
Provides vo release. An object of the invention is also to provide an abuse-resistant oral
pharmaceutical formulation comprising a pharmacologically active agent and a controlled
release carrier system. However, the formulation is suitable for use in a BID dosing regimen.
A relevant object of the present invention is the respective steady-state C min I C rna with in
vivo pharmacological performance of about 2-3 or less when administered at a
therapeutically effective dose or AUC.
8
In another embodiment, the present invention provides the formulations described above,
characterized by having ,- variation. A related object of the present invention is also to
provide the formulations described above, wherein the controlled release carrier system
further provides a reduced risk of misuse or abuse, eg, such misuse or abuse. The reduced
risk is the low in vitro solvent extraction rate of the activator from the formulation and
/alternatively, it is characterized by having no significant effect on the absorption of the
activator from the formulation when the subject co~ingests the fomiulation with alcohol. For
each relevant object of the invention described above, the controlled release carrier system
can be further characterized by a unique set of pharmaceutical excipients including solvents,
carrier materials, and viscosity enhancers. In certain preferred embodiments, the activator can
be an opioid, CNS inhibitor, or CNS stimulant, which is particularly likely to be abused,
diverted, or otherwise misused. Preferably, the activator can include opioids, amphetamines,
or methylphenidate as either salts or free bases in either case.
A further object of the present invention is to provide an abuse-resistant oral pharmaceutical
preparation containing a. pharmacologically active agent· and a controlled release carrier
, system. The controlled release carrier system is in a steady state C min within each dosing
interval.
I C max fluctuation is less than or equal to the therapeutic index of the active agent, and the
active agent in vi from the formulation
Control of agents characterized in that vo absorption is enhanced when the formulation is
administered with food, but the formulation is still safe even when ingested without
prescribing, eg, without food. Provides in vivo release. It is also an object of the present
invention to . provide an abuse-resistant oral ·pharmaceutical formulation compnsmg a
pharmacologically active agent and a controlled release carrier system. However, the
formulation is suitable for use in a BID administration regimen, and the. in vivo absorption of
the activator from the formulation
It is enhanced when the preparation is administered with food. A related object of the present
invention is to provide the above-described formulations characterized by having each
steady-state C min I C max variation in in vivo pharmacological performance of about 2-3 or
less. Is. A related object of the present invention is also to provide the formulations described
above, wherein the controlled release carrier system further provides a reduced risk of misuse
9
or abuse, eg, for such rriisuse or abuse. The reduced risk has a low in vitro solvent extraction
rate of the active agent from the formulation and I or has any significant effect on the
absorption of the active agent from the formulation when the subject co-ingests the
formulation with alcohol. Characterized by the absence. For each relevant object of the
invention described above, the controlled release carrier system can be further characterized
by a unique set of pharmaceutical excipients including solvents, carrier materials, network
structure forming agents, and viscosity enhancers. In certain preferred embodiments, the
activator is abused. It can be an opioid, CNS inhibitor, or CNS stimulant that is particularly
likely to be diverted or misused. Preferably, the activator is eit~er a salt or a free base in each
case, it can include opioids, amphetamines, or methylphenidate.
In another embodiment, the · present invention · is to offer an abuse-deterrent oral
pharmaceutical preparation that includes an opioid analgesic and a controlled release carrier
system. The controlled release carrier system maintains steady-state Cmin/Cmax fluctuations
within each dosing interval below the therapeutic index of the analgesic agent, and provides
controlled in vivo release of the opioid analgesic from the carrier system, with a T max of at
least 4 hours after ingestion by the subject. Another related objective of the present invention
is to provide an abus·e-deterrent oral pharmaceutical preparation that is suitable for BID
(twice daily) dosing regimen and characterized by a T max of at least about 4 hours after
ingestion by the subject for in vivo release of opioid analgesics from controlled release carrier
systems.
In further embodiment; the present invention provide formulations that exhibit enhanced
absorption when administered with food, or alternatively, controlled release of opioid
analgesics from the carrier system without being affected by food. Another objective is to
offer formulations with steady-state C mi_n I C max fluctuations of 2-3 or less, and reduced
risk of misuse or abuse, as indicated by low in vitro solvent extraction rate of opioid
analgesics and no significant effect on absorption when co-ingested with alcohol. Each of
these objectives can be achieved through a unique set of pharmaceutical excipients, including
solvents, carrier materials,· network structure forming agents, and viscosity enhancers, that
form the controlled release carrier system.
The present iiwention is to provide an oral pharmaceutical preparation that is abuse-resistant
and contains a controlled release carrier system along with a pharmacologically active agent.
The. controlled release carrier system is designed to provide steady-state C min I C max
10
fluctuations within each administration interval that are equal to or less than the therapeutic·
index of the active agent. It comprises a high-viscosity liquid carrier material (HVLCM), a
network structUre-forming agent, and at least one viscosity enhancer to ensure controlled in
vivo release of the agent.
Another objective of the present invention is to provide an abuse-resistant oral
pharmaceutical formulation that includes a pharmacologically active agent and a controlled
release carrier system. The formulations are appropriate for use in BID dosing regimens, and
the controlled release carrier system comprises a high viscosity liquid carrier material
(HVLCM), a network structure-forming agent, and at least one viscosity enhancer.
Additionally, a related objective of the present invention is to provide in vivo activation from
a formulation. The controlled release carrier system can be characterized by a unique set of
pharmaceutical excipients that include solvents, carrier materials, network structure forming
agents, and viscosity enhancers.
The present invention further· provide the fomiulations described above with a controlled
release carrier system . that offers a lower risk of abuse· or misuse. This reduced risk is
achieved by having a low in vitro solvent extraction rate of the. active agent from the
formulation and no significant effect on the absorption of the active agent when the
formulation is co-administered with alcohol. The controlled release carrier system can be
further characterized by a unique combination of pharmaceutical excipients, including
solvents and viscosity enhancers. In some preferred embodiments, the active agent may be an
opioid, CNS inhibitor, or CNS stimulant, which is substances that are more likely to be
abused, diverted, or misused. The active agent may be opioids, amphetamines, or
methylphenidate, either as a salt or a free base.
Oral pharmaceutical formulation that is abuse-resistant, and includes a controlled release
carrier system for a pharmacologically active agent. The· controlled release carrier syst~m
maintains a steady-state Cmin!Cmax variation within each dosing interval, which is less than
the therapeutic index of the active agent. Specifically, the Cmin!Cmax variation is about 2-3
or less, ensuring controlled release of the agent.
11
The invention also aims to provide a formulation suitable for twice-daily dosing, wherein in
vivo absorption of the active agent from the controlled release carrier system is characterized
by a T max of at least 4 hours after ingestion by the subject. In addition, the in vivo
absorption of the agent is enhanced when the formulation is administered with food.
Furthermore, the invention provides formulations that are substantially free of food effects
and have reduced risk of misuse or abuse, without significantly affecting the in vitro solvent
extraction rate of the active agent or absorption of the active agent from the formulation when .
co-ingested with alcohol.
The controlled release carrier system includes a unique set of pharmaceutical excipients
comprising a particular combination of solvents, viscosity enhancers, and other components.
The pharmacologically active agent can be any drug that is prone to misuse or abuse, such as
opioids, CNS inhibitors, or CNS stimulants, preferably opioids, amphetamines, or
methylphenidate as salts or free bases.
The invention also provides an abuse-resistant oral pharmaceuticaf preparation that includes a
controlled release carrier system comprising a high . viscosity liquid carrier material
(HVLCM), a network. structure forming agent, and at least one viscosity enhancing agent.
The formulation enhances in vivo absorption of the active agent when co-administered with
food and is substantially free of food effects. The controlled release carrier system also
provides reduced risk of misuse or abuse without significantly affecting the in vitro solvent
extraction rate of the active agent or absorption of the active agent from. the formulation when
co-administered with alcohol.
The controlled release carrier system comprises a unique set of pharmaceutical excipients that
include a combination of solvents, viscosity enhancers, and other components. The invention
also provides an oral pharmaceutical preparation comprising a controlled release carrier
system that provides a constant in vitro activator release for at least 8 hours when tested on a
USP Type II Dissolution Apparatus with a fixed basket assembly using a paddle rate of 100
rpm and a O.lN HCl dissolution medium containing a detergent. Additionally, the carrier
system provides in vitro extraction of. the active agent of less than 20% at ambient
temperature.
12
The controlled release carrier system of the oral pharmaceutical preparation comprises
HVLCM, a network structure forming agent, a rheology regulator, and a hydrophilic agent,
along with other components like viscositY enhancers, solvents, and stabilizers. In certain
embodiments, sucrose acetate isobutyrate (SAIB) is included in the HVLCM.
The present invention provides a method that is characterized by having a variation in the
maximum concentration of the drug in the body (Cmax). The objective of the invention is to
provide formulations that have a reduced risk of misuse or abuse, with low in vitro solvent
extraction rate of the drug from the formulation, and/or no significant effect on the absorption
of the drug when taken with alcohol. Another objective is ·to provide a method for ensuring
and maintaining analgesia in a subject by repeated administration of an abuse-resistant oral
analgesic preparation. The bioavailability of analgesics is enhanced when the formulation is
co-administered with food.
The formulation comprises a controlled release carrier system and an analgesic, containing a
HVLCM, a reticular structure forming agent, and at least one viscosity enhancer. The
formulations provide safer therapeutic methods and are therefore abuse-resistant. The
controlled release carrier system further provides controlled in vivo release of analgesics,
characterized. by steady-state Cmin/Cmax fluctuations within each dosing interval· that are
less than or equal to the ·therapeutic index of analgesics.
The present invention also provides a method for ensuring and maintaining analgesia in a
subject by repeated administration of an oral analgesic preparation suitable for use in a BID
dosing regimen. The in vivo pharmacological performance of the formulation has each
steady-state Cmin/Cmax variation of about 2-3 or less, and provides enhanced safety
properties and/or abuse resistance in addition to enhanced in vivo pharmacological
performance as compared to conventional formulations .
.
The present invention is advantageous because the formulations provide a safer and more
potent pharmacological.solution. The invention provides a broader range of medical solutions
that can be easily constructed and used in the medical field. The invention includes a
controlled release carrier system containing a high viscosity liquid carrier material, a
reticulated structure forming agent, a rheology adjuster, a hydrophilic agent, and a solvent,
along with an oral pharmaceutical preparation containing a pharmacological activator.
13
We claim:
1. An oral pharmaceutical preparation compnsmg ·a pharmacologically active agent and a
controlled release carrier system, wherein the· controlled release carrier system comprises a
high viscosity liquid carrier material ("HVLCM"), a network structure forming agent, a
· rheology regulator, a hydrophilic agent, and a solvent, and imparts abuse resistance to the
formulation, wherein the in vivo absorption of the active agent from the formulation is
enhanced when the formulation is administered with "toed and the in vivo release of the
active agent from the controlled release carrier system is substa'ntially free from food
effects.
2. The oral pharmaceutical preparation of claim 1, wherein the controlled release carrier
system further comprises at least one viscosity enhancer and a stabilizer.
3. The oral pharmaceutical preparation of claim 1 or 2, wherein the HVLCM comprises sucrose
acetate isobutyrate ("SAIB") and the network structure forming agent comprises cellulose
acetate butyrate ("CAB"), cellulose acetate phthalate, ethyl cellulose, hydroxypropyl methyl
cellulose, or cellulose triacetate.
4. The oral pharmaceutical preparation of any of claims 1 to 3, wherein the rheology regulator
comprises isopropyl myristate ("IPM"), capricyl/capric acid triglyceride, ethyl oleate, triethyl
citrate, dimethyl phthalate, or benzyl benzoate.
5. The oral pharmaceutical preparation of any of claims 1 to 4, wherein the hydrophilic agent
comprises hydroxyethyl cellulose ("HEC"), hydroxypropyl cellulose, carboxymethyl cellulose,
polyet/:lylene glycol, or polyvinylpyrrolidone; and the solvent comprises triacetin, N-r'nethyl-
2-pyrrolidone, 2-pyrrolidone, dimethyl sulfoxide, ethyl lactate, propylene carbonate, or
glycoflor.
6. The oral pharmaceutical preparation of any of claims 1 to 5, wherein· the viscosity enhancer
comprises silicon dioxide and the stabilizer comprises butylhydroxytoluene ("BHT").
7. The oral pharmaceutical preparation of any of claims 1 to 6, wherein the pharmacologically
active agent comprises an opioid, CNS inhibitor, or CNS stimulant, which is particularly likely
to be abused, diverted, or otherwise misused, and preferably comprises opioids,
amphetamines, or methylphenidate as either salts or free bases in either case.
8. A process for preparing an oral pharmaceutical preparation comprising a pharmacologically
active agent and a controlled release carrier system, comprising mixing the
pharmacologically active agent with a high viscosity liquid carrier material, a network
structure forming agent, a rheology regulator, a hydrophilic agent, and a solvent to form the
controlled release carrier system, and incorporating the controlled release carrier system
into a suitable dosage· form, wherein the controlled release carrier system imparts abuse
resistance to the formulation, and in vivo absorption of the active agent from the
.formulation is enhanced when the formulation is administered with food and in vivo release
of the active agent from the controlled release carrier system is substantially free from food
effects.
9. An abuse-resistant oral J>harmaceutical preparation comprising a pharmacologically active
agent and a controlled release carrier system, wherein the controlled release carrier system
is in a steady state C min within each dosing interval and C inax fluctuation is less than or
equal to the therapeutic index of the active agent.