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Compounding AlteredCompounding Altered--Release PharmaceuticalsRelease Pharmaceuticals

Part IVPart IV

Loyd V. Allen, Jr., Ph.D.Loyd V. Allen, Jr., Ph.D.

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Compounding AlteredCompounding Altered--Release Release PharmaceuticalsPharmaceuticals--Part IVPart IV

ParenteralParenteralMiscellaneousMiscellaneousDrug Examples that are Good CandidatesDrug Examples that are Good CandidatesExcipientsExcipients Used For AlteredUsed For Altered--Release Release PharmaceuticalsPharmaceuticalsSummary/ConclusionsSummary/Conclusions

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Compounding AlteredCompounding Altered--ReleaseReleasePharmaceuticalsPharmaceuticals--Part IVPart IV

ParenteralParenteral–– InternalInternal–– ExternalExternal–– IV DripIV Drip–– IM InjectionIM Injection

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Compounding Compounding ParenteralsParenterals

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InternalInternal

Factors AffectingFactors Affecting–– Particle sizeParticle size–– ConcentrationConcentration–– Diffusion coefficientsDiffusion coefficients–– Partition coefficientsPartition coefficients–– SolubilitySolubility

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InternalInternal

Mechanism of ReleaseMechanism of ReleaseStabilityStabilityEquipment RequiredEquipment RequiredMaterials/MatricesMaterials/MatricesPreparation MethodsPreparation Methods

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HydromorphoneHydromorphone 2% and 2% and BupivacaineBupivacaine HClHCl 0.75% 0.75% IntrathecalIntrathecal Injection, PFInjection, PF

HydromorphoneHydromorphone HClHCl USPUSP 2 g2 gBupivacaineBupivacaine HClHCl UspUsp 750 mg750 mg0.9% Sodium chloride 0.9% Sodium chloride injinj 42 mL42 mLSterile water for injection qsSterile water for injection qs 100 mL100 mL

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Morphine sulfate 20 mg/mL and Morphine sulfate 20 mg/mL and ClonidineClonidine HClHCl 10 10 ug/mLug/mL

Epidural InjectionEpidural Injection

Morphine sulfateMorphine sulfate 2 g 2 g ClonidineClonidine HClHCl 1 mg1 mg0.9% Sodium chloride injection 0.9% Sodium chloride injection 69 mL69 mLSterile water for injectionSterile water for injection qsqs 100 mL100 mL

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IV Drip/InfusionIV Drip/Infusion

Factors AffectingFactors Affecting–– ConcentrationConcentration–– Diffusion coefficientsDiffusion coefficients–– Partition coefficientsPartition coefficients–– SolubilitySolubility

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IV Drip/InfusionIV Drip/Infusion

Mechanism of ReleaseMechanism of ReleaseStabilityStabilityEquipment RequiredEquipment RequiredMaterials/MatricesMaterials/MatricesPreparation MethodsPreparation Methods

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IM InjectionIM Injection

Factors AffectingFactors Affecting–– Particle sizeParticle size–– ConcentrationConcentration–– Diffusion coefficientsDiffusion coefficients–– Partition coefficientsPartition coefficients–– SolubilitySolubility

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IM InjectionIM Injection

Mechanism of ReleaseMechanism of ReleaseStabilityStabilityEquipment RequiredEquipment RequiredMaterials/MatricesMaterials/MatricesPreparation MethodsPreparation Methods

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Progesterone 100 mg/mL in Oil Progesterone 100 mg/mL in Oil InjectionInjection

ProgesteroneProgesterone 10 g10 gBenzyl benzoateBenzyl benzoate 10 mL10 mLBenzyl alcoholBenzyl alcohol 10 mL10 mLSesame oilSesame oil qsqs 100 mL100 mL

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ExternalExternal

Factors AffectingFactors Affecting–– Particle sizeParticle size–– ConcentrationConcentration–– Diffusion coefficientsDiffusion coefficients–– Partition coefficientsPartition coefficients–– SolubilitySolubility

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ExternalExternal

Mechanism of ReleaseMechanism of ReleaseStabilityStabilityEquipment RequiredEquipment RequiredMaterials/MatricesMaterials/MatricesPreparation MethodsPreparation Methods

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Ambulatory PumpsAmbulatory Pumps

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CeftazidimeCeftazidime 20 mg/mL for 20 mg/mL for Ambulatory Infusion PumpAmbulatory Infusion Pump

CeftazidimeCeftazidime 2.5 g2.5 gSterile water for injectionSterile water for injection qsqs0.9% Sodium chloride 0.9% Sodium chloride injinj qsqs 125 mL125 mL

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Compounding AlteredCompounding Altered--Release Release PharmaceuticalsPharmaceuticals

MiscellaneousMiscellaneous–– Soaking a membrane or gelatin in solution Soaking a membrane or gelatin in solution

(casting)(casting)–– CyclodextrinsCyclodextrins–– ImplantsImplants–– NanoparticlesNanoparticles–– Resealed ErythrocytesResealed Erythrocytes–– Antibiotic Bone CementAntibiotic Bone Cement–– Antibiotic Beads ImplantedAntibiotic Beads Implanted–– SelfSelf--Regulated Chelating AgentsRegulated Chelating Agents

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Soaking A Membrane or Gelatin Soaking A Membrane or Gelatin in Solution (Casting)in Solution (Casting)

Factors AffectingFactors Affecting–– Particle sizeParticle size–– ConcentrationConcentration–– Diffusion coefficientsDiffusion coefficients–– Partition coefficientsPartition coefficients–– SolubilitySolubility

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Soaking A Membrane or Gelatin Soaking A Membrane or Gelatin in Solution (Casting)in Solution (Casting)

Mechanism of ReleaseMechanism of ReleaseStabilityStabilityEquipment RequiredEquipment RequiredMaterials/MatricesMaterials/MatricesPreparation MethodsPreparation Methods

Topical ApplicationTopical Application

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CyclodextrinsCyclodextrins

Factors AffectingFactors Affecting–– Particle sizeParticle size–– ConcentrationConcentration–– Diffusion coefficientsDiffusion coefficients–– Partition coefficientsPartition coefficients–– SolubilitySolubility

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CyclodextrinsCyclodextrins

Mechanism of ReleaseMechanism of ReleaseStabilityStabilityEquipment RequiredEquipment RequiredMaterials/MatricesMaterials/MatricesPreparation MethodsPreparation Methods

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ImplantsImplants

Factors AffectingFactors Affecting–– Particle sizeParticle size–– ConcentrationConcentration–– Diffusion coefficientsDiffusion coefficients–– Partition coefficientsPartition coefficients–– SolubilitySolubility

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ImplantsImplants

Mechanism of ReleaseMechanism of ReleaseStabilityStabilityEquipment RequiredEquipment RequiredMaterials/Matrices (Mg Stearate, PLA, PGA, Materials/Matrices (Mg Stearate, PLA, PGA, Silicone Polymers)Silicone Polymers)Preparation MethodsPreparation Methods

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Fibrin GlueFibrin Glue

AprotininAprotinin 70,000 KIU70,000 KIUThrombinThrombin 10,000 IU10,000 IUCalcium chloride 0.5 M solCalcium chloride 0.5 M sol 2 mL2 mL

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NanoparticlesNanoparticles

Factors AffectingFactors Affecting–– Particle sizeParticle size–– ConcentrationConcentration–– Diffusion coefficientsDiffusion coefficients–– Partition coefficientsPartition coefficients–– SolubilitySolubility

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NanoparticlesNanoparticles

Mechanism of ReleaseMechanism of ReleaseStabilityStabilityEquipment RequiredEquipment RequiredMaterials/MatricesMaterials/MatricesPreparation MethodsPreparation Methods

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Resealed ErythrocytesResealed Erythrocytes

Factors AffectingFactors Affecting–– Particle sizeParticle size–– ConcentrationConcentration–– Diffusion coefficientsDiffusion coefficients–– Partition coefficientsPartition coefficients–– SolubilitySolubility

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Resealed ErythrocytesResealed Erythrocytes

Mechanism of ReleaseMechanism of ReleaseStabilityStabilityEquipment RequiredEquipment RequiredMaterials/MatricesMaterials/MatricesPreparation MethodsPreparation Methods

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Resealed ErythrocytesResealed Erythrocytes

Whole BloodWhole BloodSpin it down and remove the red blood cellsSpin it down and remove the red blood cellsPlace in sterile hypotonic saline or waterPlace in sterile hypotonic saline or waterAdd concentrated sterile solution of drugAdd concentrated sterile solution of drugReadjust tonicity to isotonicReadjust tonicity to isotonicErythrocytes will Erythrocytes will ““resealreseal””Administer to patientAdminister to patient………….last up to 3 weeks.last up to 3 weeks

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Antibiotic Bone CementAntibiotic Bone Cement

Factors AffectingFactors Affecting–– Particle sizeParticle size–– ConcentrationConcentration–– Diffusion coefficientsDiffusion coefficients–– Partition coefficientsPartition coefficients–– SolubilitySolubility

Mechanism of ReleaseMechanism of ReleaseStabilityStabilityEquipment RequiredEquipment RequiredMaterials/Matrices (Materials/Matrices (PalacosPalacos Bone Cement + Drug)Bone Cement + Drug)Preparation MethodsPreparation Methods

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TobramycinTobramycin--Impregnated Impregnated PolymethylmethacrylatePolymethylmethacrylate BeadsBeads

TobramycinTobramycin sulfatesulfate 1.2 g1.2 gPalacosPalacos Bone CementBone Cement 40 g40 g

0.25 inch beads contain approx 3.26 mg of 0.25 inch beads contain approx 3.26 mg of tobramycintobramycin (as the sulfate)(as the sulfate)

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VancomycinVancomycin 5 mg Sponge Disks5 mg Sponge Disks

VancomycinVancomycin HClHCl 5 mg5 mgSponge (collagen or gelatin)Sponge (collagen or gelatin) qsqs

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Compounding AlteredCompounding Altered--Release Release PharmaceuticalsPharmaceuticals

Drug Examples That Are Good CandidatesDrug Examples That Are Good CandidatesThe lower the dose the betterThe lower the dose the betterLower solubility is betterLower solubility is betterShort halfShort half--life life vsvs long halflong half--lifelifeLarge therapeutic indexLarge therapeutic index

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Drug Examples That Are Good Drug Examples That Are Good CandidatesCandidates

SolubilitySolubilityDoseDoseADMEADME----Duration of actionDuration of actionPharmacokineticsPharmacokinetics

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Compounding AlteredCompounding Altered--Release Release PharmaceuticalsPharmaceuticals

Summary/ConclusionsSummary/ConclusionsYES, some are feasibleYES, some are feasibleNo, some are notNo, some are notQuality Control is importantQuality Control is importantAlways monitor clinical responseAlways monitor clinical response

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A LOOK INTO THEA LOOK INTO THENEAR FUTURENEAR FUTURE

New Compounded Drug Delivery Systems New Compounded Drug Delivery Systems (DDS)(DDS)Next 5Next 5--10 years10 years

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Future TrendsFuture Trends

Adhesive SiteAdhesive Site--Specific DDSSpecific DDSAntibodyAntibody--Based DDSBased DDSBiocompatible Biocompatible MicrosphereMicrosphere DDSDDSBiodegradable Polymers DDSBiodegradable Polymers DDSBiologicBiologic--Based DDSBased DDSElectromagnetic/RadiationElectromagnetic/Radiation--Activated DDSActivated DDS

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Future TrendsFuture Trends

ImmunomodulatorImmunomodulator DDSDDSImplantImplant--Enhanced DDSEnhanced DDSMicroorganismMicroorganism--Containing MicrocapsulesContaining MicrocapsulesLipid Lipid MicrocylindersMicrocylindersLiposome EnhancementsLiposome EnhancementsLivingLiving--Cell TherapiesCell Therapies

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Future TrendsFuture Trends

Magnetic System DDSMagnetic System DDSMazeMaze--Escape DDSEscape DDSMonoclonal Antibody DDSMonoclonal Antibody DDSNovel Nasal DDSNovel Nasal DDSNew Osmotic DDSNew Osmotic DDSTransmucosalTransmucosal DDSDDSPolymer Drug Complex DDSPolymer Drug Complex DDS

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Future TrendsFuture Trends

PulsatilePulsatile DDSDDSRespiratory DDSRespiratory DDSSelfSelf--Assembling Controlled Release DDSAssembling Controlled Release DDSProgrammed Skin Surface DDSProgrammed Skin Surface DDS

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