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A semi-solid delivery vehicle contains a polyorthoester and an excipient, and a semi-solid pharmaceutical composition contains an active agent and the delivery vehicle. The pharmaceutical composition may be a topical, syringable, or injectable formulation; and is suitable for local delivery of the a

A semi-solid delivery vehicle contains a polyorthoester and an excipient, and a semi-solid pharmaceutical composition contains an active agent and the delivery vehicle. The pharmaceutical composition may be a topical, syringable, or injectable formulation; and is suitable for local delivery of the active agent. Methods of treatment are also disclosed.

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1. A pharmaceutical composition, comprising:(a) an active agent; and(b) a semi-solid delivery vehicle comprising:(i) a polyorthoester of formula I or formula II where:R is a bond, —(CH 2 ) a —, or —(CH 2 ) b —O—(CH 2 ) c —; where a is an integer

1. A pharmaceutical composition, comprising:(a) an active agent; and(b) a semi-solid delivery vehicle comprising:(i) a polyorthoester of formula I or formula II where:R is a bond, —(CH 2 ) a —, or —(CH 2 ) b —O—(CH 2 ) c —; where a is an integer of 1 to 10, and b and c are independently integers of 1 to 5;R* is a C 1-4 alkyl;n is an integer of at least 5; andA is R 1 , R 2 , R 3 , or R 4 , whereR 1 is: where:p is an integer of 1 to 20;R 5 is hydrogen or C 1-4 alkyl; andR 6 is: where:s is an integer of 0 to 30;t is an integer of 2 to 200; andR 7 is hydrogen or C 1-4 alkyl;R 2 is:R 3 is: where:x is an integer of 0 to 30;y is an integer of 2 to 200;R 8 is hydrogen or C 1-4 alkyl;R 9 and R 10 are independently C 1-12 alkylene;R 11 is hydrogen or C 1-6 alkyl and R 12 is C 1-6 alkyl; or R 11 and R 12 together are C 3-10 alkylene; andR 4 is a diol containing at least one functional group independently selected from amide, imide, urea, and urethane groups; in which at least 0.1 mol percent of the A units are of the formula R 1 , and(ii) a pharmaceutically acceptable, polyorthoester-compatible liquid excipient selected from polyethylene glycol ether derivatives having a molecular weight between 200 and 4000, polyethylene glycol copolymers having a molecular weight between 400 and 4000, mono-, di-, or tri-glycerides of a C 2-19 aliphatic carboxylic acid or a mixture of such acids, alkoxylated tetrahydrofurfuryl alcohols and their C 1-4 alkyl ethers and C 2-19 aliphatic carboxylic acid esters, and biocompatible oils. 2. The composition of claim 1 where the concentration of the polyorthoester ranges from 1% to 99% by weight of the delivery vehicle. 3. The composition of claim 1 where the polyorthoester has a molecular weight between 1000 and 20,000. 4. The composition of claim 1 where the fraction of the A units that are of the formula R 1 is between 1 and 90 mol percent. 5. The composition of claim 1 where the polyorthoester is of formula I, where:none of the units have A equal to R 2 ;R 3 is: where:x is an integer of 0 to 10;y is an integer of 2 to 30; andR 6 is: where:s is an integer of 0 to 10;t is an integer of 2 to 30; andR 5 , R 7 , and R 8 are independently hydrogen or methyl. 6. The composition of claim 5 where:R 3 and R 6 are both —(CH 2 —CH 2 —O) 2 —(CH 2 —CH 2 )—;R 5 is methyl; andp is 1 or 2. 7. The composition of claim 5 where:R 3 and R 6 are both —(CH 2 —CH 2 —O) 9 —(CH 2 —CH 2 )—;R 5 is methyl; andp is 1 or 2. 8. The composition of claim 1 where the fraction of the active agent is from 1% to 60% by weight of the composition. 9. The composition of claim 8 where the fraction of the active agent is from 5% to 30% by weight of the composition. 10. The composition of claim 1 where the composition is in topical, syringable, or injectable form. 11. The composition of claim 1 where the active agent is selected from anti-infectives, antiseptics, steroids, therapeutic polypeptides, anti-inflammatory agents, cancer chemotherapeutic agents, narcotics, local anesthetics, antiangiogenic agents, vaccines, antigens, DNA, and antisense oligonucleotides. 12. The composition of claim 11 where the active agent is a therapeutic polypeptide. 13. The composition of claim 12 where the active agent is bone morphogenic protein. 14. The composition of claim 11 where the active agent is a local anesthetic. 15. The composition of claim 14 further comprising a glucocorticosteroid. 16. The composition of claim 11 where the active agent is an antiangiogenic agent. 17. The composition of claim 11 where the active agent is a cancer chemotherapeutic agent. 18. The composition of claim 11 where the active agent is an antibiotic. 19. The composition of claim 11 where the active agent is an anti-inflammatory agent. 20. A method o f treating a disease state treatable by controlled release local administration of an active agent, comprising locally administering a therapeutically effective amount of the active agent in the form of a pharmaceutical composition of claim 1. 21. The method of claim 20 where the active agent is selected from anti-infectives, antiseptics, steroids, therapeutic polypeptides, anti-inflammatory agents, cancer chemotherapeutic agents, narcotics, local anesthetics, antiangiogenic agents, vaccines, antigens, DNA, and antisense oligonucleotides. 22. A method of preventing or relieving local pain at a site in a mammal, comprising administering to the site a therapeutically effective amount of a local anesthetic in the form of a pharmaceutically acceptable composition of claim 14. 23. A method of preventing or relieving local pain at a site in a mammal, comprising administering to the site a therapeutically effective amount of a local anesthetic in the form of a pharmaceutically acceptable composition of claim 15. 24. A process for the preparation of the pharmaceutical composition of claim 1 where the active agent is in solid form, comprising:(1) optionally milling the active agent to reduce the particle size of the active agent;(2) mixing the active agent and the delivery vehicle; and(3) optionally milling the composition to reduce the particle size of the active agent.